76 results on '"Nachiappan V"'
Search Results
2. Control of Alcoholism by Treatment with SKV, A Herbal Drug Mixture from India
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Nachiappan, V., Shanmugasundaram, K. R., Mufti, S. I., Alling, Christer, editor, Diamond, Ivan, editor, Leslie, Steven W., editor, Sun, Grace Y., editor, and Wood, W. Gibson, editor
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- 1993
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3. Remote Diagnosis of the Patient through IOT and Virtual Reality, Classification of the Cloud Data Using ANN
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Nachiappan, V. Alagammai, primary, esh, Raj, additional, and Devaraj, Rajalakshmi, additional
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- 2021
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4. Digital biomarker of mental fatigue
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Vincent Wen-Sheng Tseng, Nachiappan Valliappan, Venky Ramachandran, Tanzeem Choudhury, and Vidhya Navalpakkam
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Computer applications to medicine. Medical informatics ,R858-859.7 - Abstract
Abstract Mental fatigue is an important aspect of alertness and wellbeing. Existing fatigue tests are subjective and/or time-consuming. Here, we show that smartphone-based gaze is significantly impaired with mental fatigue, and tracks the onset and progression of fatigue. A simple model predicts mental fatigue reliably using just a few minutes of gaze data. These results suggest that smartphone-based gaze could provide a scalable, digital biomarker of mental fatigue.
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- 2021
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5. Tools for semi-formal proofs
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Nachiappan, Nachiappan V., Sinzinger, Eric D., and Rushton, J. Nelson
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Software engineering ,Formal methods ,Computing education ,Software correctness - Abstract
We propose a semi-formal proof structure, in which the overall arrangement of a proof is a formal data structure, while individual propositions within the structure are expressed either formally or informally. We hypothesize that such proofs are easier to check accurately, compared with standard informal prose proofs. Our framework is conceptually simple, and proofs written in it look similar to informal proofs. We also give the definitions and the main theorem on the correctness of our structure-checking algorithm. The theorem is essentially that the proofs accepted by our algorithm are indeed correct. The thesis also includes an empirical study which involves experimentation of our proposed version of semi-formal proof structure in comparison to traditionally written prose proofs. If our hypothesis is correct, the system should be easier for students to learn, and yield intuitions that can be more effectively leveraged toward reading actual proofs in computer science literature.
- Published
- 2008
6. Accelerating eye movement research via accurate and affordable smartphone eye tracking
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Nachiappan Valliappan, Na Dai, Ethan Steinberg, Junfeng He, Kantwon Rogers, Venky Ramachandran, Pingmei Xu, Mina Shojaeizadeh, Li Guo, Kai Kohlhoff, and Vidhya Navalpakkam
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Science - Abstract
Progress in eye movement research has been limited since existing eye trackers are expensive and do not scale. Here, the authors show that smartphone-based eye tracking achieves high accuracy comparable to state-of-the-art mobile eye trackers, replicating key findings from prior eye movement research.
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- 2020
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7. ETHANOL-MEDIATED PROMOTION OF OESOPHAGEAL CARCINOGENESIS: ASSOCIATION WITH LIPID PEROXIDATION AND CHANGES IN PHOSPHOLIPID FATTY ACID PROFILE OF THE TARGET TISSUE
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MUFTI, S. I., primary, NACHIAPPAN, V., additional, and ESKELSON, C. D., additional
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- 1997
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8. Enzymatic Synthesis of [32P]Acyl-sn-glycerol 3-Phosphate Using Diacylglycerol Kinase
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Nachiappan, V., primary and Rajasekharan, R., additional
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- 1994
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9. Use of Photoreactive Substrates for Characterization of Lysophosphatidate Acyltransferases from Developing Soybean Cotyledons
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Rajasekharan, R., primary and Nachiappan, V., additional
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- 1994
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10. CYTOKINES INHIBIT FATTY ACID OXIDATION IN ISOLATED RAT HEPATOCYTES
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Nachiappan, V., primary, Curtiss, D., additional, Corkey, B. E., additional, and Kilpatrick, L., additional
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- 1994
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11. Alpha-1-antichymotrypsin inhibits the NADPH oxidase-enzyme complex in phorbol ester-stimulated neutrophil membranes.
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Kilpatrick, L, primary, McCawley, L, additional, Nachiappan, V, additional, Greer, W, additional, Majumdar, S, additional, Korchak, H M, additional, and Douglas, S D, additional
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- 1992
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12. Evaluation of antihyperlipidemic activity of ethanolic extract of Cassia auriculata flowers
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Panneerselvam Vijayaraj, Muthukumar, K., Sabarirajan, J., and Nachiappan, V.
13. Induction of acute respiratory distress syndrome in rats by lipopolysaccharide and its effect on oxidative stress and antioxidant status in lung
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Sabarirajan, J., Panneerselvam Vijayaraj, and Nachiappan, V.
14. Alcohol as a risk factor in B-cell lymphoproliferative disorders
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Mufti, S.I., Odeleye, O.E., and Nachiappan, V.
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Alcohol -- Physiological aspects ,Lymphoproliferative disorders -- Risk factors ,Business ,Health care industry - Abstract
AUTHORS: S.I. Mufti, O.E. Odeleye and V. Nachiappan. Departments of Pharmacology and Toxicology and Family and Community Medicine, University of Arizona, Tucson, Arizona. According to an abstract presented during an [...]
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- 1993
15. Impairment of RPN4, a transcription factor, induces ER stress and lipid abnormality in Saccharomyces cerevisiae.
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Nagaraj B, James AW, Mathivanan A, and Nachiappan V
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- Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae metabolism, Endoplasmic Reticulum Stress, Lipids, DNA-Binding Proteins metabolism, Transcription Factors genetics, Transcription Factors metabolism, Saccharomyces cerevisiae Proteins genetics
- Abstract
Accumulation of misfolded/unfolded proteins in the endoplasmic reticulum (ER) induces ER stress. The transcription factor RPN4 {"Regulatory Particle Non-ATPase"} regulates protein homeostasis by degrading proteins that elude proper folding or assembly via the proteasomal degradation pathway. Here, we studied the lipid alterations exerted by Saccharomyces cerevisiae to mitigate (ER) stress during adaptive responses in rpn4∆ cells. The loss of RPN4-induced ER stress increased phospholipid synthesis, leading to altered membrane structures and accumulation of neutral lipids, causing an increase in lipid droplets (LDs). There was a significant upregulation of genes involved in neutral lipid and membrane lipid synthesis in rpn4∆ cells. Overexpression of RPN4 restored the defects caused by rpn4∆ cells. Thus, our study provides new insight that RPN4 impacts lipid homeostasis., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2023
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16. Deletion of ORM2 Causes Oleic Acid-Induced Growth Defects in Saccharomyces cerevisiae.
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Mathivanan A and Nachiappan V
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- Oleic Acid, Fatty Acids, Nonesterified metabolism, Sphingolipids metabolism, Phospholipids, Lipid Metabolism, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae metabolism, Saccharomyces cerevisiae Proteins genetics, Saccharomyces cerevisiae Proteins metabolism
- Abstract
The endoplasmic reticulum (ER) resident proteins of the Orm family (Orm1p and Orm2p) play an essential regulatory role in sphingolipid metabolism and proteostasis of Saccharomyces cerevisiae. Sphingolipid metabolism and its relationship with yeast ORM1 and ORM2 have been studied widely, but its position in phospholipids and neutral lipids requires further studies. We found that the deletion of ORM2 reduced phospholipid levels, but orm1Δ had shown no significant alteration of phospholipids. On the contrary, neutral lipid levels and lipid droplet (LD) numbers were increased in both orm1∆ and orm2∆ cells. Unlike orm1Δ, free fatty acid (FFA) levels were steeply accumulated in orm2∆ cells, and deletion of ORM2 made the cells more sensitive towards oleic acid toxicity. Misregulation of fatty acids has been implicated in the causation of several lipid metabolic disorders. It is imminent to comprehend the control mechanisms of free fatty acid homeostasis and its pathophysiology. Our study has provided experimental evidence of ORM2 role in the lipid and fatty acid metabolism of yeast., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2023
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17. Therapeutic Target Analysis and Molecular Mechanism of Melatonin - Treated Leptin Resistance Induced Obesity: A Systematic Study of Network Pharmacology.
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Suriagandhi V and Nachiappan V
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- Humans, Molecular Docking Simulation, Network Pharmacology, Obesity drug therapy, Obesity genetics, Obesity metabolism, Leptin genetics, Leptin metabolism, Melatonin metabolism, Melatonin pharmacology, Melatonin therapeutic use
- Abstract
Background: Obesity is a medical problem with an increased risk for other metabolic disorders like diabetes, heart problem, arthritis, etc. Leptin is an adipose tissue-derived hormone responsible for food intake, energy expenditure, etc., and leptin resistance is one of the significant causes of obesity. Excess leptin secretion by poor diet habits and impaired hypothalamic leptin signaling leads to LR. Melatonin a sleep hormone; also possess antioxidant and anti-inflammatory properties. The melatonin can attenuate the complications of obesity by regulating its targets towards LR induced obesity., Aim: The aim of this study includes molecular pathway and network analysis by using a systems pharmacology approach to identify a potential therapeutic mechanism of melatonin on leptin resistance-induced obesity., Methods: The bioinformatic methods are used to find therapeutic targets of melatonin in the treatment of leptin resistance-induced obesity. It includes target gene identification using public databases, Gene ontology, and KEGG pathway enrichment by 'ClusterProfiler' using the R language, network analysis by Cytoscape, and molecular Docking by Autodock., Results: We obtained the common top 33 potential therapeutic targets of melatonin and LR-induced obesity from the total melatonin targets 254 and common LR obesity targets 212 using the data screening method. They are involved in biological processes related to sleep and obesity, including the cellular response to external stimulus, chemical stress, and autophagy. From a total of 180 enriched pathways, we took the top ten pathways for further analysis, including lipid and atherosclerosis, endocrine, and AGE-RAGE signaling pathway in diabetic complications. The top 10 pathways interacted with the common 33 genes and created two functional modules. Using Cytoscape network analysis, the top ten hub genes (TP53, AKT1, MAPK3, PTGS2, TNF, IL6, MAPK1, ERBB2, IL1B, MTOR) were identified by the MCC algorithm of the CytoHubba plugin. From a wide range of pathway classes, melatonin can reduce LR-induced obesity risks by regulating the major six classes. It includes signal transduction, endocrine system, endocrine and metabolic disease, environmental adaptation, drug resistance antineoplastic, and cardiovascular disease., Conclusion: The pharmacological mechanism of action in this study shows the ten therapeutic targets of melatonin in LR-induced obesity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Suriagandhi and Nachiappan.)
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- 2022
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18. Impairment of transcription factor Gcr1p binding motif perturbs OPI3 transcription in Saccharomyces cerevisiae.
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Chidambaram R, Ramachandran G, Rajasekharan R, and Nachiappan V
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- DNA-Binding Proteins genetics, Gene Expression Regulation, Fungal, Protein Binding, Transcription Factors genetics, DNA-Binding Proteins metabolism, Phosphatidylethanolamine N-Methyltransferase genetics, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae metabolism, Saccharomyces cerevisiae Proteins genetics, Saccharomyces cerevisiae Proteins metabolism, Transcription Factors metabolism
- Abstract
In Saccharomyces cerevisiae, the transcription factor GCR1 plays a vital role in carbohydrate metabolism and in the current study we tried to elucidate its role in lipid metabolism. In silico analysis revealed the upstream activation sequence (UAS) in the promoter region of OPI3 possessed six conserved recognition sequences for Gcr1p and the ChIP assay confirmed the binding of Gcr1p on the OPI3 promoter region. The real-time quantitative polymerase chain reaction and promoter-reporter activity revealed a substantial reduction in OPI3 expression and was supported with decreased phosphatidylcholine (PC) level that is rescued with exogenous choline supplementation in gcr1∆ cells. Simultaneously, there was an increase in triacylglycerol level, accompanied with increased number and size of lipid droplets in gcr1∆ cells. The expression of pT1, pT2 truncations in opi3∆ cells revealed the -1 to -500 bp in the promoter region is essential for the activation of OPI3 transcription. The mutation specifically at UAS
CT box (-265) in the OPI3 promoter region displayed a reduction in the PC level and the additional mutation at UASINO (-165) further reduced the PC level. Collectively, our data suggest that the GCR1 transcription factor also regulates the OPI3 expression and has an impact on lipid homeostasis., (© 2022 Wiley Periodicals LLC.)- Published
- 2022
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19. Protective Effects of Melatonin against Obesity-Induced by Leptin Resistance.
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Suriagandhi V and Nachiappan V
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- Circadian Rhythm drug effects, Humans, Hypothalamus physiology, Leptin blood, Obesity etiology, Appetite drug effects, Leptin metabolism, Melatonin metabolism, Obesity metabolism
- Abstract
Consumption of an exceedingly high-fat diet with irregular eating and sleeping habits is typical in the current sedentary lifestyle, leading to chronic diseases like obesity and diabetes mellitus. Leptin is a primary appetite-regulating hormone that binds to its receptors in the hypothalamic cell membrane and regulates downstream appetite-regulating neurons NPY/AgRp and POMC in the hypothalamus. Based on the fat content of the adipose tissue, leptin is secreted, and excess accumulation of fat in adipose tissue stimulates the abnormal secretion of leptin. The secreted leptin circulating in the bloodstream uses its transporters to cross the blood-brain barrier (BBB) and reach the CSF. There is a saturation limit for leptin bound to its transporters to cross the BBB, and increased leptin secretion in adipose tissue has a defect in its transport across the BBB. Leptin resistance is due to excess leptin, a saturation of its transporters, and deficiency in either the receptor level or signalling in the hypothalamus. Leptin resistance leads to obesity due to excess food intake and less energy expenditure. Normal leptin secretion follows a rhythm, and alteration in the lifestyle leads to hormonal imbalances and increases ROS generation leading to oxidative stress. The sleep disturbance causes obesity with increased lipid accumulation in adipose tissue. Melatonin is the master regulator of the sleep-wake cycle secreted by the pineal gland during the night. It is a potent antioxidant with anti-inflammatory properties. Melatonin is secreted in a pattern called the circadian rhythm in humans as well. Research indicates that melatonin plays a vital role in hormonal regulation and energy metabolism, including leptin signalling and secretion. Studying the role of melatonin in leptin regulation will help us combat the pathologies of obesity caused by leptin resistance., (Copyright © 2021 Elsevier B.V. All rights reserved.)
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- 2022
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20. Human OVCA2 and its homolog FSH3-induced apoptosis in Saccharomyces cerevisiae.
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Gowsalya R, Ravi C, and Nachiappan V
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- Gene Expression Regulation, Fungal genetics, Humans, Membrane Potential, Mitochondrial genetics, Mitochondria genetics, Mitochondria metabolism, Reactive Oxygen Species metabolism, Saccharomyces cerevisiae genetics, Apoptosis genetics, Apoptosis Regulatory Proteins genetics, Cell Cycle genetics, Proteins genetics, Saccharomyces cerevisiae Proteins genetics
- Abstract
Mammalian ovarian tumor suppressor candidate 2 (OVCA2) gene belongs to the family of serine hydrolase (FSH). This study aimed to elucidate the functional similarities of OVCA2 with its yeast homolog genes (FSH1, FSH2, and FSH3) regarding apoptosis. We found that the expression of OVCA2 in Saccharomyces cerevisiae increased production of reactive oxygen species (ROS), decreased cell growth, disturbed mitochondrial morphology, reduced membrane potential, increased chromatin condensation, and externalization of phosphatidylserine (PS) (annexin V/propidium iodide staining) indicating induced apoptotic cell death in yeast. We also showed that complementation of OVCA2 in fsh3Δ cells reduced cell growth and increased the apoptotic phenotypes. Collectively, our results suggest that complementation of human OVCA2 in fsh3Δ cells induced apoptosis in S. cerevisiae.
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- 2021
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21. Hydroquinone exposure accumulates neutral lipid by the activation of CDP-DAG pathway in Saccharomyces cerevisiae .
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Raj A and Nachiappan V
- Abstract
Benzene metabolites (HQ and BQ) are toxic compounds and their presence in human cause alteration in cellular respiration and kidney damage. In the current study, Saccharomyces cerevisiae has been used as a model organism and acute exposure of hydroquinone (HQ) decreased cell growth and increased reactive oxygen species (ROS). The expression of apoptosis regulatory genes ( YCA1 , NUC1 , YSP1 and AIF1 ) were increased with HQ exposure in the wild-type cells. HQ exposure in the wild-type cells altered both the phospholipid and neutral lipid levels. Phosphatidylcholine is a vital membrane lipid that has a vital role in membrane biogenesis and was increased significantly with HQ. The neutral lipid results were supported with lipid droplets data and mRNA expression study. The phospholipid knockouts (Kennedy pathway) accumulated neutral lipids via the CDP-DAG (cytidine-diphosphate-diacylglycerol) pathway genes both in the presence and absence of HQ., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
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- 2021
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22. FSH1 encodes lysophospholipase activity in Saccharomyces cerevisiae.
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Ramachandran G, Chidambaram R, and Nachiappan V
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- Lipid Droplets metabolism, Lipid Metabolism genetics, Lysophospholipids metabolism, Phospholipids metabolism, Lysophospholipase genetics, Lysophospholipase metabolism, Saccharomyces cerevisiae enzymology, Saccharomyces cerevisiae metabolism, Saccharomyces cerevisiae Proteins genetics, Saccharomyces cerevisiae Proteins metabolism, Serine Proteases genetics, Serine Proteases metabolism
- Abstract
Objectives: To elucidate the role of FSH1 (family of serine hydrolase) in lipid homeostasis., Results: Proteins in various species containing alpha/beta hydrolase domain are known to be involved in lipid metabolism. In silico analysis of the FSH1 gene in Saccharomyces cerevisiae revealed the presence of alpha/beta hydrolase domain (ABHD) and a lipase motif (GXSXG), however its function in lipid metabolism remained elusive. The overexpression of FSH1 in WT and fsh1Δ cells showed a significant reduction in the cellular phospholipid levels and an increase in the triacylglycerol levels and lipid droplet (LD) number. Furthermore, the purified recombinant protein Fsh1p was identified as a lysophospholipase that specifically acts on lysophosphatidylserine (LPS) and impacts the lipid homeostasis in S. cerevisiae., Conclusions: These results depicted that Fsh1p has a role on lipid homeostasis and is a lysophospholipase that hydrolyzes lysophosphatidylserine (LPS).
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- 2021
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23. Loss of ERAD bridging factor UBX2 modulates lipid metabolism and leads to ER stress-associated apoptosis during cadmium toxicity in Saccharomyces cerevisiae.
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Rajakumar S, Vijayakumar R, Abhishek A, Selvam GS, and Nachiappan V
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- Carrier Proteins genetics, Endoplasmic Reticulum metabolism, Gene Expression Regulation, Fungal, Genes, Fungal, Lipid Droplets metabolism, Membrane Lipids metabolism, Mitochondria drug effects, Mitochondria ultrastructure, Phospholipids metabolism, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae growth & development, Saccharomyces cerevisiae physiology, Saccharomyces cerevisiae Proteins genetics, Triglycerides metabolism, Unfolded Protein Response, Apoptosis, Cadmium toxicity, Carrier Proteins metabolism, Endoplasmic Reticulum Stress, Endoplasmic Reticulum-Associated Degradation, Lipid Metabolism, Saccharomyces cerevisiae drug effects, Saccharomyces cerevisiae Proteins metabolism
- Abstract
The endoplasmic reticulum (ER) stress potentially activates the unfolded protein response (UPR) and ER-associated protein degradation (ERAD) as quality-control mechanisms. During ERAD process, the ERAD adaptor protein Ubx2 serves as a bridging factor and transports the misfolded proteins from the ER to the cytosol for subsequent ubiquitylation and proteasomal degradation. Cadmium (Cd) is a toxic metal that initiates ER stress and has an impact on lipid homeostasis and this study focuses on the synergistic impact of Cd exposure and ERAD (using ubx2∆ strain). With Cd exposure in ubx2∆ strain, we observed stunted growth and induction of ER stress. The ER stress was confirmed by measuring the expression of UPR marker (Kar2p), and mRNA expression of ER stress-responsive genes (HAC1, IRE1, ERO1, and PDI1), heat shock responsive genes (HSP104 and HSP60), ERAD pathway genes (DOA10, CDC48, HRD1, and YOS9), and proteasome regulators (UBI14, and RPN4). We also observed aberrant membrane morphology with DiOC6 staining, and interrupted mitochondria with mitotracker dye using microscopic analysis. The cell's inability to relieve stress through adaptive response results in apoptosis and was assessed using acridine orange (AO)-ethidium bromide (EtBr) staining. In ubx2∆ strain, there was reduction in triacylglycerol (TAG) and lipid droplets (LDs), and increase in the phospholipids. The mRNA expression of lipid metabolic genes (LRO1, DGA1, ARE1, ARE2, and OLE1) supported the lipid pattern observed. Collectively, our data suggest that in Saccharomyces cerevisiae, the Cd exposure on ubx2∆ strain induced cellular stress and has an impact on ERAD, UPR, and LD homeostasis.
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- 2020
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24. Impairment of MET transcriptional activators, MET4 and MET31 induced lipid accumulation in Saccharomyces cerevisiae.
- Author
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Rajakumar S, Suriyagandhi V, and Nachiappan V
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- Gene Deletion, Lipogenesis, Saccharomyces cerevisiae metabolism, Basic-Leucine Zipper Transcription Factors genetics, DNA-Binding Proteins genetics, Lipid Metabolism, Methionine metabolism, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae Proteins genetics, Transcription Factors genetics
- Abstract
The genes involved in the methionine pathway are closely associated with phospholipid homeostasis in yeast. The impact of the deletion of methionine (MET) transcriptional activators (MET31, MET32 and MET4) in lipid homeostasis is studied. Our lipid profiling data showed that aberrant phospholipid and neutral lipid accumulation occurred in met31∆ and met4∆ strains with low Met. The expression pattern of phospholipid biosynthetic genes such as CHO2, OPI3 and triacylglycerol (TAG) biosynthetic gene, DGA1 were upregulated in met31∆, and met4∆ strains when compared to wild type (WT). The accumulation of triacylglycerol and sterol esters (SE) content supports the concomitant increase in lipid droplets in met31∆ and met4∆ strains. However, excessive supplies of methionine (1 mM) in the cells lacking the MET transcriptional activators MET31 and MET4 ameliorates the abnormal lipogenesis and causes aberrant lipid accumulation. These findings implicate the methionine accessibility plays a pivotal role in lipid metabolism in the yeast model., (© FEMS 2020.)
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- 2020
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25. Disruption in phosphate transport affects membrane lipid and lipid droplet homeostasis in Saccharomyces cerevisiae.
- Author
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Subitha M, James AW, Sivaprakasam C, and Nachiappan V
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- Homeostasis, Saccharomyces cerevisiae, Lipid Droplets metabolism, Membrane Lipids metabolism
- Abstract
Phosphate plays a crucial role in phospholipid metabolism and it is transported by the phosphate (Pi) transporters. Phospholipids are building blocks of the cell membrane, and essential for cell growth; however, the role of phosphate transporters in lipid metabolism remains elusive. The present study shows that the deletion of Pi transporters exhibited an increase in both phospholipid and neutral lipid levels when compared to wild type. The mRNA expressions of genes involved in phospholipid synthesis (CKI1, EKI1, CHO2, and OPI3) were increased due to de-repression of the transcription factors (INO2 and INO4). Neutral lipid levels (triacylglycerol and sterol ester) and their synthesizing genes (LRO1, ARE2, ACC1, and FAS1) were also increased, resulting in lipid droplet accumulation in Pi transporter mutants. Interestingly, phospholipase (PLC1) and histone acetyltransferase genes (ESA1, EAF1, YNG1, YNG2, and GCN5) were also found to be significantly increased, leading to dysregulation of lipid levels in Pi transporter mutants. In summary, our results suggest that the Pi transporters are involved in lipid droplet and membrane lipid homeostasis.
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- 2020
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26. Effect of cadmium on essential metals and their impact on lipid metabolism in Saccharomyces cerevisiae.
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Rajakumar S, Abhishek A, Selvam GS, and Nachiappan V
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- Homeostasis drug effects, Saccharomyces cerevisiae metabolism, Saccharomyces cerevisiae Proteins metabolism, Zinc pharmacology, Cadmium toxicity, Endoplasmic Reticulum Stress drug effects, Lipid Metabolism drug effects, Saccharomyces cerevisiae Proteins drug effects
- Abstract
Cadmium (Cd) is a toxic heavy metal that induces irregularity in numerous lipid metabolic pathways. Saccharomyces cerevisiae, a model to study lipid metabolism, has been used to establish the molecular basis of cellular responses to Cd toxicity in relation to essential minerals and lipid homeostasis. Multiple pathways sense these environmental stresses and trigger the mineral imbalances specifically calcium (Ca) and zinc (Zn). This review is aimed to elucidate the role of Cd toxicity in yeast, in three different perspectives: (1) elucidate stress response and its adaptation to Cd, (2) understand the physiological role of a macromolecule such as lipids, and (3) study the stress rescue mechanism. Here, we explored the impact of Cd interference on the essential minerals such as Zn and Ca and their influence on endoplasmic reticulum stress and lipid metabolism. Cd toxicity contributes to lipid droplet synthesis by activating OLE1 that is essential to alleviate lipotoxicity. In this review, we expanded our current findings about the effect of Cd on lipid metabolism of budding yeast.
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- 2020
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27. FSH1 overexpression triggers apoptosis in Saccharomyces cerevisiae.
- Author
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Gowsalya R, Ravi C, Arul M, and Nachiappan V
- Subjects
- Endonucleases biosynthesis, Exonucleases biosynthesis, Gene Deletion, Microbial Viability, NADH, NADPH Oxidoreductases biosynthesis, Saccharomyces cerevisiae Proteins genetics, Serine Proteases genetics, Apoptosis, Gene Expression, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae growth & development, Saccharomyces cerevisiae Proteins biosynthesis, Serine Proteases biosynthesis
- Abstract
FSH1 belongs to the family of serine hydrolases in yeast and is homologous to the human ovarian tumor suppressor gene (OVAC2). Our preliminary results showed that cells lacking Fsh1p exhibit an increase in cell growth, and a decrease in the expression of AIF1 and NUC1 (apoptosis responsive genes) when compared to the wild type cells. Growth inhibition of cells overexpressing FSH1 is due to induction of cell death associated with cell death markers typical of mammalian apoptosis namely DNA fragmentation, phosphatidylserine externalization, ROS accumulation, Cytochrome c release, and altered mitochondrial membrane potential. When wild type cells were overexpressed with FSH1 there was up regulation of AIF1 level when compared to control cells suggesting that overexpression of FSH1 regulated cell death in yeast.
- Published
- 2019
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28. Benzoquinone alters the lipid homeostasis in Saccharomyces cerevisiae .
- Author
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Raj A and Nachiappan V
- Abstract
Objective : To elucidate the impact of benzoquinone (BQ) on lipid homeostasis and cytotoxicity in Saccharomyces cerevisiae . Methods : The impact of BQ exposure on wild-type and knockouts of PC biosynthesizing genes revealed the alterations in the lipids that were analyzed by fluorescence microscopy, thin layer chromatography, and gene expression studies . Results : In yeast, BQ exposure reduced the growth pattern in wild-type cells. The gene knockout strains of the phospholipid metabolism altered the mRNA expression of the apoptosis genes - both caspase-dependent and independent. The BQ exposure revealed an increase in both the phospholipids and neutral lipids via the CDP:DAG and the Kennedy pathway genes. The accumulation of both neutral lipids and phospholipids during the BQ exposure was discrete and regulated by different pathways. Conclusions : BQ exposure inhibited cell growth, increased the reactive oxygen species (ROS), and altered membrane proliferation. The CDP:DAG and Kennedy pathway lipids also discretely altered by BQ, which is required for the membrane functions and energy purposes of life., (This journal is © The Royal Society of Chemistry 2019.)
- Published
- 2019
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29. Crosstalk between protein N-glycosylation and lipid metabolism in Saccharomyces cerevisiae.
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William James A, Ravi C, Srinivasan M, and Nachiappan V
- Subjects
- Endoplasmic Reticulum metabolism, Endoplasmic Reticulum Stress genetics, Gene Expression Regulation, Fungal, Genes, Fungal, Glycosylation, Membrane Lipids metabolism, Models, Biological, Mutation, Peroxisomes genetics, Peroxisomes metabolism, Phospholipids metabolism, Phosphotransferases (Alcohol Group Acceptor) genetics, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae growth & development, Saccharomyces cerevisiae Proteins genetics, Sterols metabolism, Unfolded Protein Response genetics, Lipid Metabolism genetics, Phosphotransferases (Alcohol Group Acceptor) metabolism, Saccharomyces cerevisiae metabolism, Saccharomyces cerevisiae Proteins metabolism
- Abstract
The endoplasmic reticulum (ER) is a multi functional organelle and plays a crucial role in protein folding and lipid biosynthesis. The SEC59 gene encodes dolichol kinase, required for protein glycosylation in the ER. The mutation of sec59-1 caused a protein N-glycosylation defect mediated ER stress resulting in increased levels of phospholipid, neutral lipid and sterol, whereas growth was reduced. In the sec59-1∆ cell, the N-glycosylation of vacuolar carboxy peptidase-Y (CPY) was significantly reduced; whereas the ER stress marker Kar2p and unfolded protein response (UPR) were significantly increased. Increased levels of Triacylglycerol (TAG), sterol ester (SE), and lipid droplets (LD) could be attributed to up-regulation of DPP1, LRO1, and ARE2 in the sec 59-1∆ cell. Also, the diacylglycerol (DAG), sterol (STE), and free fatty acids (FFA) levels were significantly increased, whereas the genes involved in peroxisome biogenesis and Pex3-EGFP levels were reduced when compared to the wild-type. The microarray data also revealed increased expression of genes involved in phospholipid, TAG, fatty acid, sterol synthesis, and phospholipid transport resulting in dysregulation of lipid homeostasis in the sec59-1∆ cell. We conclude that SEC59 dependent N-glycosylation is required for lipid homeostasis, peroxisome biogenesis, and ER protein quality control.
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- 2019
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30. Impaired GCR1 transcription resulted in defective inositol levels, vacuolar structure and autophagy in Saccharomyces cerevisiae.
- Author
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Ravi C, Gowsalya R, and Nachiappan V
- Subjects
- Binding Sites, DNA-Binding Proteins chemistry, Gene Expression Regulation, Fungal genetics, Glycolysis genetics, Inositol genetics, Inositol metabolism, Promoter Regions, Genetic, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae Proteins chemistry, Transcription Factors chemistry, Vacuoles genetics, Vacuoles ultrastructure, Autophagy genetics, DNA-Binding Proteins genetics, Saccharomyces cerevisiae Proteins genetics, Transcription Factors genetics, Transcription, Genetic
- Abstract
In yeast, the GCR1 transcription factor is involved in the regulation of glycolysis and its deletion exhibited growth defect, reduced inositol and phosphatidylinositol (PI) levels compared to WT cells. We observed a down regulation of the INO1 and PIS1 expression in gcr1∆ cells under both I- and I+ conditions and the over expression of GCR1 in gcr1∆ cells restored the growth, retrieved the expression of INO1, and PIS1 comparable to WT cells. In the gel shift assay, the Gcr1p binds to its consensus sequence CTTCC in PIS1 promoter and regulates its expression but not in INO1 transcription. The WT cells, under I- significantly reduced the expression of GCR1 and PIS1, but increased the expression of KCS1 and de-repressed INO1. The Kcs1p expression was reduced in gcr1∆ cells; this reduced INO1 expression resulting in abnormal vacuolar structure and reduced autophagy in Saccharomyces cerevisiae.
- Published
- 2019
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31. FSH3 mediated cell death is dependent on NUC1 in Saccharomyces cerevisiae.
- Author
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Gowsalya R, Ravi C, Kannan M, and Nachiappan V
- Subjects
- Apoptosis, Apoptosis Regulatory Proteins genetics, Endonucleases genetics, Exonucleases genetics, Hydrogen Peroxide, Hydrolases genetics, Microbial Viability, Reactive Oxygen Species metabolism, Saccharomyces cerevisiae growth & development, Saccharomyces cerevisiae Proteins genetics, Serine, Apoptosis Regulatory Proteins metabolism, Endonucleases metabolism, Exonucleases metabolism, Hydrolases metabolism, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae Proteins metabolism
- Abstract
Family of Serine Hydrolases (FSH) members FSH1, FSH2 and FSH3 in Saccharomyces cerevisiae share conserved sequences with the human candidate tumor suppressor OVCA2. In this study, hydrogen peroxide (H2O2) exposure increased the expression of both mRNA and protein levels of FSH3 in wild-type (WT) yeast cells. The deletion of FSH3 improved the yeast growth rate under H2O2-induction as compared to WT control cells. The overexpression of FSH3 in WT yeast cells caused an apoptotic phenotype, including accumulation of reaction oxygen species, decreased cell viability and cell death. The double deletions fsh1Δ fsh2Δ, fsh1Δ fsh3Δ and fsh2Δ fsh3Δ displayed increased growth compared to WT cells. However, the overexpression of FSH3 effectively inhibited cell growth in all double deletions. Moreover, the overexpression of FSH3 in cells lacking NUC1 did not cause any growth defect in the presence or absence of H2O2. Our results suggest that FSH3 induced apoptosis of yeast in a NUC1 dependent manner., (© FEMS 2019.)
- Published
- 2019
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32. Cassia auriculata flower extract attenuates hyperlipidemia in male Wistar rats by regulating the hepatic cholesterol metabolism.
- Author
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Vijayakumar R and Nachiappan V
- Subjects
- ATP Binding Cassette Transporter 1 metabolism, Animals, Bile Acids and Salts metabolism, Biosynthetic Pathways drug effects, Biosynthetic Pathways genetics, Cholesterol blood, Ethanol, Gene Expression Regulation drug effects, Hyperlipidemias blood, Lipogenesis genetics, Male, Plant Extracts pharmacology, RNA, Messenger genetics, RNA, Messenger metabolism, Rats, Wistar, Cassia chemistry, Cholesterol metabolism, Flowers chemistry, Hyperlipidemias drug therapy, Liver metabolism, Plant Extracts therapeutic use
- Abstract
Hyperlipidemia in the male albino Wistar rats was induced by Triton WR - 1339. The treatment of the hyperlipidemic animals with the ethanol extract of Cassia auriculata flower (Et-CAF) exhibited a dose dependent reduction in serum triacylglycerol, total cholesterol, low density lipoprotein (LDL), very low density lipoprotein (VLDL) similar to the hyperlipidemic animals treated with standard drug atorvastatin. Hyperlipidemia altered the protein and mRNA expression levels of the key genes (SREBP-1c, ACC1, SREBP-2, HMGR, HMGS, CYP7A1, and ABCA1) in lipid metabolism and the treatment with Et-CAF (300mg/kg b. wt) reverted these levels similar to that observed with atorvastatin treated hyperlipidemic animals. These results revealed that Et-CAF extract served as an efficient anti-hyperlipidemic drug., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)
- Published
- 2017
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33. Antihyperlipidemic activity of Cassia auriculata flower extract in oleic acid induced hyperlipidemia in Saccharomyces cerevisiae .
- Author
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Rajendran V, Krishnegowda A, and Nachiappan V
- Abstract
The Cassia auriculata herb has been traditionally used in India for medicinal purposes to treat hyperglycemia, diabetes, rheumatism, asthma, and skin diseases. In the present study, ethanolic extract of Cassia auriculata flower (Et-CAF) depicted anti-hyperlipidemic effect in the budding yeast cells. The hyperlipidemic conditions were induced in the yeast cells with oleic acid which showed an increase in triacylglycerol (TAG) and sterol esters (SE), and was supported by the mRNA expression of LRO1 and DGA1 (involved in TAG formation); as well as ARE1 and ARE2 (involved in SE formation). The anti-hyperlipidemic effect by the Et-CAF was compared with the commercial drug Atorvastatin. The lipid droplets were increased in the hyperlipidemic yeast cell that was observed under the confocal microscope with BODIPY staining; Atorvastatin and Et-CAF reduced the lipid droplets. This study revealed that the anti-hyperlipidemic effect in Et-CAF has gained importance and might be used to fill the gap created by the allopathic drugs.
- Published
- 2017
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34. Endoplasmic reticulum stress affects the transport of phosphatidylethanolamine from mitochondria to the endoplasmic reticulum in S.cerevisiae.
- Author
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Kannan M, Sivaprakasam C, Prinz WA, and Nachiappan V
- Subjects
- Biological Transport drug effects, Dithiothreitol pharmacology, Endoplasmic Reticulum drug effects, Endoplasmic Reticulum Stress drug effects, Mitochondria drug effects, Mitochondrial Membranes drug effects, Mitochondrial Membranes metabolism, Mitophagy drug effects, Phosphatidylcholines metabolism, Phospholipids metabolism, Saccharomyces cerevisiae drug effects, Saccharomyces cerevisiae Proteins metabolism, Biological Transport physiology, Endoplasmic Reticulum metabolism, Endoplasmic Reticulum physiology, Endoplasmic Reticulum Stress physiology, Mitochondria metabolism, Phosphatidylethanolamines metabolism, Saccharomyces cerevisiae metabolism
- Abstract
Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) are two of the most abundant phospholipids in cells. Although both lipids can be synthesized in the endoplasmic reticulum (ER), in S. cerevisiae PE can also be produced in mitochondria and endosomes; this PE can be transported back to the ER where it is converted to PC. In this study we found that dithiothreitol (DTT), which induces ER stress, decreases PE export from mitochondria to the ER. This results in decreased levels of total cellular PC and mitochondrial PC. These decreases were not caused by changes in levels of PC synthesizing or degrading enzymes. PE export from mitochondria to the ER during ER stress was further reduced in cells lacking Mdm10p, a component of an ER-mitochondrial tethering complex that may facilitated lipid exchange between these compartments. We also found that reducing mitochondrial PC levels induces mitophagy. In conclusion, we show that ER stress affected PE export from mitochondria to ER and the Mdm10p is important for this process., (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Published
- 2016
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35. Dolichyl pyrophosphate phosphatase-mediated N-glycosylation defect dysregulates lipid homeostasis in Saccharomyces cerevisiae.
- Author
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James AW, Gowsalya R, and Nachiappan V
- Subjects
- Blotting, Western, Cathepsin A metabolism, Cell Membrane metabolism, Endoplasmic Reticulum Stress, Fluorescence, Gene Expression Regulation, Fungal, Genes, Fungal, Genetic Complementation Test, Glycosylation, Green Fluorescent Proteins metabolism, Lipid Droplets metabolism, Mutation genetics, Phenotype, Phospholipids metabolism, Phosphotransferases (Alcohol Group Acceptor) metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae growth & development, Time Factors, Unfolded Protein Response, Dolichol Phosphates metabolism, Homeostasis, Lipid Metabolism genetics, Pyrophosphatases metabolism, Saccharomyces cerevisiae enzymology, Saccharomyces cerevisiae Proteins metabolism
- Abstract
The endoplasmic reticulum (ER) has numerous biological functions including protein synthesis, protein folding, and lipid synthesis. The CAX4 gene encodes dolichyl pyrophosphate (Dol-PP) phosphatase, which is involved in protein N-glycosylation. In cax4Δ cells, the N-glycosylation of the vacuolar carboxypeptidase (CPY) was severely affected, and expression of the ER chaperone Kar2p was elevated, which resulted in UPR activation as an adaptive response. The cax4Δ cell growth was reduced, and this could be attributed to the formation of clumped aggregates, high vesiculation of the intracellular membrane, and plasma membrane alterations were depicted using DiOC6 fluorescence. In the cax4 deletion strain, the transcription factors INO2 and INO4 were upregulated, and the negative regulator OPI1 was concomitantly down regulated, which led to the derepression of the phospholipid genes CHO2, OPI3, PSD1, and PSD2 and resulted in increased phospholipid levels. However, the TAG, SE, and LD levels were significantly reduced, and FFA, sterol, and DAG levels were increased. These findings could be attributed to the derepression of the TAG and SE lipases TGL3, TGL4, TGL5, YEH1, and YEH2 and the repression of LRO1, DGA1, ARE1, and ARE2 in cax4Δ cells. Interestingly, the overexpression of SEC59 or CAX4 in cax4Δ cells prevented the ER stress and growth defect, and restored normal level of phospholipids, neutral lipids, and LDs. The current study revealed the disruption of N-glycosylation-induced ER stress, altered lipid homeostasis accounts for pleiotropic phenotype. Thus, CAX4 regulates membrane biogenesis by coordinating lipid homeostasis with protein quality control., (Copyright © 2016. Published by Elsevier B.V.)
- Published
- 2016
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36. Lipid droplets alleviate cadmium induced cytotoxicity in Saccharomyces cerevisiae .
- Author
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Rajakumar S and Nachiappan V
- Abstract
Cadmium (Cd) induces oxidative stress that generates reactive oxygen species (ROS) and increased lipid accumulation. However, very little is known about the role of oxidative stress in triacylglycerol (TAG) accumulation. TAG accumulation is deleterious to health and may result in obesity-associated metabolic syndrome. Hence TAG accumulation plays an important role in Cd induced cytotoxicity. The exposure of Wild-type (WT) cells to Cd, resulted in TAG accumulation and also enhanced viability when compared to TAG mutants ( dga1 Δ, lro1 Δ and are2 Δ). The inhibition of lipolysis also increased the tolerance of the cells to Cd. Fluorescence microscopy observations using acridine orange and DHR123 staining demonstrated that the TAG deficient mutants showed enhanced cell death and ROS production. The over expression of DGA1 and LRO1 rescued the Cd induced cytotoxicity by enhancing the formation of LDs. Results of this study revealed the possible metabolic link between LDs and oxidative stress in S. cerevisiae .
- Published
- 2016
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37. Alteration of mitochondrial phospholipid due to the PLA 2 activation in rat brains under cadmium toxicity.
- Author
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Sivaprakasam C, Vijayakumar R, Arul M, and Nachiappan V
- Abstract
Cadmium (Cd) is a heavy metal that has received considerable environmental and occupational concern. Cd causes toxic effects due to its accumulation in a variety of tissues, including the kidney, liver and the nervous system (CNS); however, the exact mechanism is poorly understood. In the present study, we tried to explore the impact of acute cadmium exposure on rat brain phospholipids (PLs). Cd exposure significantly reduced PLs in a time dependent manner and the reduction was due to the activation of the Phospholipase A
2 enzymes (sPLA2 , cPLA2 ). The release of arachidonic acid from PLs increased during inflammatory conditions by PLA2 s. The mRNA expression of cyclooxygenase2 (COX2) and subsequently the pro-inflammatory cytokines, namely, Interleukin 1 (IL-1) and IL-6, were up regulated; however, the expression of anti-inflammatory cytokine IL-10 was reduced in a time dependent manner. The expression of the Tumor necrosis factor alpha (TNF-α), Inducible nitric oxide synthase (iNOS) and Interferon gamma (INF-γ) also experienced increases in the expression. Likewise the mRNA expression of the pro-apoptotic factor, Bcl-2-associated X protein (Bax), was elevated, whereas anti-apoptosis B-cell lymphoma 2 (Bcl2) was down regulated. This present study might help to decipher the effects of cadmium toxicity on rat brain.- Published
- 2016
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38. Modulatory effect of cadmium on the expression of phospholipase A2 and proinflammatory genes in rat testis.
- Author
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Sivaprakasam C and Nachiappan V
- Subjects
- Animals, Cyclooxygenase 2 genetics, Cyclooxygenase 2 metabolism, Down-Regulation drug effects, Electrophoresis, Gel, Two-Dimensional, Interferon-gamma genetics, Interferon-gamma metabolism, Interleukin-10 genetics, Interleukin-10 metabolism, Interleukin-6 genetics, Interleukin-6 metabolism, Male, Membrane Potential, Mitochondrial drug effects, Mitochondria drug effects, Mitochondria metabolism, Nitric Oxide Synthase Type II metabolism, Proto-Oncogene Proteins c-bcl-2 metabolism, RNA, Messenger metabolism, Rats, Rats, Wistar, Reverse Transcriptase Polymerase Chain Reaction, Testis metabolism, Tumor Necrosis Factor-alpha genetics, Tumor Necrosis Factor-alpha metabolism, Up-Regulation drug effects, bcl-2-Associated X Protein metabolism, Cadmium toxicity, Gene Expression drug effects, Phospholipases A2 metabolism, Testis drug effects
- Abstract
Cadmium (Cd) is a toxic metal that is hazardous to health, and its exposure showed a significant reduction in mitochondrial phospholipid function in the rat testes. Cd induction enhanced phospholipases (PLA2 s) activities, specifically the secretory PLA2 and cytosolic PLA2 . There was a reduction in mitochondrial membrane potential and significant decline in the respiratory complexes, which was confirmed by 2D blue native gel. The mRNA expression of cyclooxygenase and proinflammatory cytokine genes interleukin (IL)-1, IL-6, tumor necrosis factor-α, inducible nitric oxide synthase, and interferon-γ increased and that of anti-inflammatory cytokine IL-10 reduced with Cd exposure in a time-dependent manner. The gene expression of the proapoptotic factor Bax was elevated, and in parallel, the antiapoptotic factor Bcl2 was down-regulated. Hence, this study explored the testes under Cd toxicity and observed alterations in PLA2 s and mitochondrial membrane composition/function and further explored the impact of these alterations on proinflammation and apoptosis. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1176-1184, 2016., (© 2015 Wiley Periodicals, Inc.)
- Published
- 2016
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39. Endoplasmic reticulum stress and calcium imbalance are involved in cadmium-induced lipid aberrancy in Saccharomyces cerevisiae.
- Author
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Rajakumar S, Bhanupriya N, Ravi C, and Nachiappan V
- Subjects
- Cell Membrane metabolism, Homeostasis, Lipid Droplets metabolism, Lipid Metabolism drug effects, Metabolic Networks and Pathways, Methylation, Phosphatidylcholines biosynthesis, Phosphatidylethanolamine N-Methyltransferase genetics, Phosphatidylethanolamine N-Methyltransferase metabolism, Saccharomyces cerevisiae drug effects, Saccharomyces cerevisiae Proteins genetics, Saccharomyces cerevisiae Proteins metabolism, Triglycerides metabolism, Unfolded Protein Response, Cadmium pharmacology, Calcium metabolism, Endoplasmic Reticulum Stress, Saccharomyces cerevisiae metabolism
- Abstract
The endoplasmic reticulum is the key organelle which controls protein folding, lipid biogenesis, and calcium (Ca(2+)) homeostasis. Cd exposure in Saccharomyces cerevisiae activated the unfolded protein response and was confirmed by the increased Kar2p expression. Cd exposure in wild-type (WT) cells increased PC levels and the PC biosynthetic genes. Deletion of the two phospholipid methyltransferases CHO2 and OPI3 modulated PC, TAG levels and the lipid droplets with cadmium exposure. Interestingly, we noticed an increase in the calcium levels upon Cd exposure in the mutant cells. This study concluded that Cd interrupted calcium homeostasis-induced lipid dysregulation leading to ER stress.
- Published
- 2016
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40. Exposure to benzene metabolites causes oxidative damage in Saccharomyces cerevisiae.
- Author
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Raj A and Nachiappan V
- Subjects
- Antioxidants metabolism, Ascorbic Acid metabolism, Catalase metabolism, Enzyme Activation drug effects, Glutathione metabolism, Glutathione Peroxidase metabolism, Lipid Metabolism drug effects, Malondialdehyde metabolism, Microscopy, Confocal, Oxidative Stress drug effects, Oxidative Stress physiology, Phospholipids metabolism, Reactive Oxygen Species metabolism, Superoxide Dismutase metabolism, Benzene pharmacology, Saccharomyces cerevisiae drug effects, Saccharomyces cerevisiae metabolism
- Abstract
Hydroquinone (HQ) and benzoquinone (BQ) are known benzene metabolites that form reactive intermediates such as reactive oxygen species (ROS). This study attempts to understand the effect of benzene metabolites (HQ and BQ) on the antioxidant status, cell morphology, ROS levels and lipid alterations in the yeast Saccharomyces cerevisiae. There was a reduction in the growth pattern of wild-type cells exposed to HQ/BQ. Exposure of yeast cells to benzene metabolites increased the activity of the anti-oxidant enzymes catalase, superoxide dismutase and glutathione peroxidase but lead to a decrease in ascorbic acid and reduced glutathione. Increased triglyceride level and decreased phospholipid levels were observed with exposure to HQ and BQ. These results suggest that the enzymatic antioxidants were increased and are involved in the protection against macromolecular damage during oxidative stress; presumptively, these enzymes are essential for scavenging the pro-oxidant effects of benzene metabolites.
- Published
- 2016
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41. Defect of zinc transporter ZRT1 ameliorates cadmium induced lipid accumulation in Saccharomyces cerevisiae.
- Author
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Rajakumar S, Ravi C, and Nachiappan V
- Subjects
- Gene Deletion, Intracellular Space metabolism, Lipid Droplets metabolism, Phospholipids metabolism, Reactive Oxygen Species metabolism, Saccharomyces cerevisiae drug effects, Saccharomyces cerevisiae growth & development, Triglycerides metabolism, Cadmium toxicity, Cation Transport Proteins metabolism, Lipid Metabolism drug effects, Saccharomyces cerevisiae metabolism, Saccharomyces cerevisiae Proteins metabolism, Zinc metabolism
- Abstract
Cadmium (Cd) is a non-essential divalent heavy metal that enters the cells by utilizing the transport pathways of the essential metals, like zinc (Zn), in Saccharomyces cerevisiae. This work focuses on Cd accumulation and its impact on deletion of Zn transporters Zrt1p and Zrt2p and lipid homeostasis. Cd exposure reduces the Zn levels in the mutant strains, and the effect was higher in zrt2Δ cells. Upon Cd exposure, the wild-type and zrt2Δ cells follow a similar pattern, but an opposite pattern was observed in zrt1Δ cells. The Cd influx and ROS levels were high in both wild-type cells and zrt2Δ cells but significantly reduced in zrt1Δ cells. Cd exposure led to accumulation of triacylglycerol and lipid droplets in wild-type cells and zrt2Δ cells but these levels were decreased in zrt1Δ cells. Hence, these studies suggest that the zrt1Δ cells provide resistance towards Cd and aid in the maintenance of lipid homeostasis in yeast cells.
- Published
- 2016
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42. MGL2/YMR210w encodes a monoacylglycerol lipase in Saccharomyces cerevisiae.
- Author
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Selvaraju K, Gowsalya R, Vijayakumar R, and Nachiappan V
- Subjects
- Amino Acid Motifs, Amino Acid Sequence, Carbon Radioisotopes, Genetic Complementation Test, Lipid Droplets metabolism, Lipoylation, Membrane Lipids metabolism, Microbial Viability, Monoacylglycerol Lipases chemistry, Mutagenesis, Site-Directed, Mutation genetics, Phospholipids metabolism, Phylogeny, Recombinant Proteins isolation & purification, Saccharomyces cerevisiae cytology, Saccharomyces cerevisiae growth & development, Saccharomyces cerevisiae Proteins chemistry, Spectrometry, Mass, Electrospray Ionization, Staining and Labeling, Monoacylglycerol Lipases metabolism, Saccharomyces cerevisiae enzymology, Saccharomyces cerevisiae Proteins metabolism
- Abstract
In silico analysis of the uncharacterized open reading frame YMR210w in Saccharomyces cerevisiae revealed that it possesses both an α/β hydrolase domain (ABHD) and a typical lipase (GXSXG) motif. The purified protein displayed monoacylglycerol (MAG) lipase activity and preferred palmitoyl-MAG. Overexpression of YMR210w in the known MAG lipase mutant yju3Δ clearly revealed that the protein had MAG lipase activity, hence we named the ORF MGL2. Overexpression of YMR210w decreased the cellular triacylglycerol levels. Analysis of the overexpressed strains showed reduction in the lipid droplets number and size. Phenotype studies revealed that the double deletion yju3Δmgl2Δ displayed a growth defect that was partially restored by MGL2 overexpression., (© 2016 Federation of European Biochemical Societies.)
- Published
- 2016
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43. ROG1 encodes a monoacylglycerol lipase in Saccharomyces cerevisiae.
- Author
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Vishnu Varthini L, Selvaraju K, Srinivasan M, and Nachiappan V
- Subjects
- Amino Acid Motifs, Gene Deletion, Monoacylglycerol Lipases chemistry, Monoacylglycerol Lipases genetics, Mutagenesis, Site-Directed, Reactive Oxygen Species metabolism, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae Proteins chemistry, Monoacylglycerol Lipases metabolism, Saccharomyces cerevisiae enzymology, Saccharomyces cerevisiae Proteins metabolism
- Abstract
Lipid metabolism is extensively studied in Saccharomyces cerevisiae. Here, we report that revertant of glycogen synthase kinase mutation-1 (Rog1p) possesses monoacylglycerol (MAG) lipase activity in S. cerevisiae. The lipase activity of Rog1p was confirmed in two ways: through analysis of a strain with a double deletion of ROG1 and monoglyceride lipase YJU3 (yju3Δrog1Δ) and by site-directed mutagenesis of the ROG1 lipase motif (GXSXG). Rog1p is localized in both the cytosol and the nucleus. Overexpression of ROG1 in a ROG1-deficient strain resulted in an accumulation of reactive oxygen species. These results suggest that Rog1p is a MAG lipase that regulates lipid homeostasis., (Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)
- Published
- 2015
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44. Identification of a phospholipase B encoded by the LPL1 gene in Saccharomyces cerevisiae.
- Author
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Selvaraju K, Rajakumar S, and Nachiappan V
- Abstract
Phospholipids also play a major role in maintaining the lipid droplet (LD) morphology. In our current study, deletion of LPL1 resulted in altered morphology of LDs and was confirmed by microscopic analysis. LPL1/YOR059c contains lipase specific motif GXSXG and acetate labeling in the LPL1 overexpressed strains depicted a decrease in glycerophospholipids and an increase in free fatty acids. The purified Lpl1p showed phospholipase activity with broader substrate specificity, acting on all glycerophospholipids primarily at sn-2 position and later at sn-1 position. Localization studies precisely revealed that Lpl1 is exclusively localized in the LD at the stationary phase. Site directed mutagenesis experiments clearly demonstrated that the lipase motif is vital for the phospholipase activity. In summary, our results demonstrate that yeast Lpl1 exerts phospholipase activity, plays a vital role in LD morphology, and its absence results in altered LD size. Based on the localization and enzyme activity we renamed YOR059c as LPL1 (LD phospholipase 1)., (Copyright © 2014 Elsevier B.V. All rights reserved.)
- Published
- 2014
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45. In vitro exposure of tobacco specific nitrosamines decreases the rat lung phospholipids by enhanced phospholipase A2 activity.
- Author
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Vijayaraj P, Sivaprakasam C, Varthini LV, Sarkar M, and Nachiappan V
- Subjects
- Animals, Lung metabolism, Male, Rats, Wistar, Lung drug effects, Nitrosamines toxicity, Phospholipases A2 metabolism, Phospholipids metabolism, Nicotiana
- Abstract
Tobacco-specific nitrosamines (TSNA) have implications in the pathogenesis of various lung diseases and conditions are prevalent even in non-smokers. N-nitrosonornicotine (NNN) and 4-(methyl nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are potent pulmonary carcinogens present in tobacco product and are mainly responsible for lung cancer. TSNA reacts with pulmonary surfactants, and alters the surfactant phospholipid. The present study was undertaken to investigate the in vitro exposure of rat lung tissue slices to NNK or NNN and to monitor the phospholipid alteration by [(32)P]orthophosphate labeling. Phospholipid content decreased significantly in the presence of either NNK or NNN with concentration and time dependent manner. Phosphatidylcholine (PC) is the main phospholipid of lung and significant reduction was observed in PC ∼61%, followed by phosphatidylglycerol (PG) with 100μM of NNK, whereas NNN treated tissues showed a reduction in phosphatidylserine (PS) ∼60% and PC at 250μM concentration. The phospholipase A2 assays and expression studies reveal that both compounds enhanced phospholipid hydrolysis, thereby reducing the phospholipid content. Collectively, our data demonstrated that both NNK and NNN significantly influenced the surfactant phospholipid level by enhanced phospholipase A2 activity., (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Published
- 2014
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46. Spectroscopic and molecular modeling studies on the interactions of N-Methylformamide with superoxide dismutase.
- Author
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Kalyani D, Jyothi K, Sivaprakasam C, and Nachiappan V
- Subjects
- Animals, Circular Dichroism, Formamides chemistry, Hydrogen Bonding, Molecular Docking Simulation, Protein Binding, Protein Structure, Secondary, Rats, Reproducibility of Results, Spectrophotometry, Ultraviolet, Spectroscopy, Fourier Transform Infrared, Superoxide Dismutase chemistry, Formamides metabolism, Models, Molecular, Superoxide Dismutase metabolism
- Abstract
N-Methylformamide, a polar solvent has a wide industrial applications and it is well-known for hepatotoxicity. The interaction between NMF with superoxide dismutase, an antioxidant defense enzyme has been studied for the first time using spectroscopic methods including Fourier transform infrared (FT-IR) spectroscopy, Circular dichroism (CD) spectroscopy and UV-visible spectroscopy under simulative physiological conditions and also by molecular modelling. Fourier Transform Infra Red analysis showed that the change in peak positions and shapes revealed that the secondary structure of SOD had been changed by the interaction with NMF. The data of CD spectra also confirmed that NMF decreased the degree of secondary structure of SOD, which directly resulted in destabilization of enzyme. We studied the inhibitory effect of NMF on enzyme kinetics by pyrogallol autoxidation revealed that protein-ligand complex caused structural unfolding which resulted in enzymatic inhibition. Thus the spectral behaviour of superoxide dismutase provides data concerning its conformational changes in the presence of NMF. Furthermore, molecular docking was applied to explore the binding mode between the protein-ligand complex. This suggested that Asn54 and Val302 residues of dimeric protein were predicted to interact with NMF. The present study provides direct evidence at a molecular level to show that exposure to NMF cause perturbation in its structure and function., (Copyright © 2014 Elsevier B.V. All rights reserved.)
- Published
- 2014
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47. Phosphate transporter mediated lipid accumulation in Saccharomyces cerevisiae under phosphate starvation conditions.
- Author
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James AW and Nachiappan V
- Subjects
- Acyltransferases metabolism, Biofuels microbiology, Biomass, Chromatography, Thin Layer, Gene Expression Regulation, Fungal drug effects, Lipids isolation & purification, Microbial Viability drug effects, Mutation genetics, Phosphates pharmacology, Saccharomyces cerevisiae drug effects, Saccharomyces cerevisiae enzymology, Saccharomyces cerevisiae growth & development, Adaptor Proteins, Vesicular Transport metabolism, Lipid Metabolism drug effects, Lipid Metabolism genetics, Phosphate Transport Proteins metabolism, Phosphates deficiency, Saccharomyces cerevisiae metabolism, Saccharomyces cerevisiae Proteins metabolism
- Abstract
In the current study, when phosphate transporters pho88 and pho86 were knocked out they resulted in significant accumulation (84% and 43%) of triacylglycerol (TAG) during phosphate starvation. However in the presence of phosphate, TAG accumulation was only around 45% in both pho88 and pho86 mutant cells. These observations were confirmed by radio-labeling, fluorescent microscope and RT-PCR studies. The TAG synthesizing genes encoding for acyltransferases namely LRO1 and DGA1 were up regulated. This is the first report for accumulation of TAG in pho88Δ and pho86Δ cells under phosphate starvation conditions., (Copyright © 2013. Published by Elsevier Ltd.)
- Published
- 2014
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48. Antihypercholesterolemic and antioxidative effects of an extract of the oyster mushroom, Pleurotus ostreatus, and its major constituent, chrysin, in Triton WR-1339-induced hypercholesterolemic rats.
- Author
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Anandhi R, Annadurai T, Anitha TS, Muralidharan AR, Najmunnisha K, Nachiappan V, Thomas PA, and Geraldine P
- Subjects
- Animals, Hypercholesterolemia chemically induced, Hypercholesterolemia prevention & control, Lipoproteins, LDL blood, Male, Rats, Rats, Wistar, Antioxidants pharmacology, Cholesterol blood, Flavonoids pharmacology, Hypercholesterolemia metabolism, Hypolipidemic Agents pharmacology, Pleurotus chemistry, Polyethylene Glycols
- Abstract
Hypercholesterolemia and oxidative stress are known to accelerate coronary artery disease and progression of atherosclerotic lesions. In the present study, an attempt was made to evaluate the putative antihypercholesterolemic and antioxidative effects of an ethanolic extract of the oyster mushroom (Pleurotus ostreatus) and chrysin, one of its major components, in hypercholesterolemic rats. Hypercholesterolemia was induced in rats by a single intraperitoneal injection of Triton WR-1339 (300 mg/kg body weight (b.wt.)), which resulted in persistently elevated blood/serum levels of glucose, lipid profile parameters (total cholesterol, triglycerides, low-density lipoprotein-, and very low-density lipoprotein-cholesterol), and of hepatic marker enzymes (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase). In addition, lowered mean activities of hepatic antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase) and lowered mean levels of nonenzymatic antioxidants (reduced glutathione, vitamin C, and vitamin E) were observed. Oral administration of the mushroom extract (500 mg/kg b.wt.) and chrysin (200 mg/kg b.wt.) to hypercholesterolemic rats for 7 days resulted in a significant decrease in mean blood/serum levels of glucose, lipid profile parameters, and hepatic marker enzymes and a concomitant increase in enzymatic and nonenzymatic antioxidant parameters. The hypercholesterolemia-ameliorating effect was more pronounced in chrysin-treated rats than in extract-treated rats, being almost as effective as that of the standard lipid-lowering drug, lovastatin (10 mg/kg b.wt.). These results suggest that chrysin, a major component of the oyster mushroom extract, may protect against the hypercholesterolemia and elevated serum hepatic marker enzyme levels induced in rats injected with Triton WR-1339.
- Published
- 2013
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49. Effect of lipopolysaccharide on alteration of phospholipids and their fatty acid composition in spleen and thymus by in vitro metabolic labeling.
- Author
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Sabarirajan J, Vijayaraj P, Sarkar M, and Nachiappan V
- Subjects
- Analysis of Variance, Animals, Autoradiography, Chromatography, Thin Layer, Isotope Labeling, Male, Phosphates metabolism, Phosphatidylcholines metabolism, Phosphatidylglycerols metabolism, Phosphorus Radioisotopes, Rats, Rats, Wistar, Spleen drug effects, Thymus Gland drug effects, Fatty Acids metabolism, Lipopolysaccharides toxicity, Phospholipids metabolism, Spleen metabolism, Thymus Gland metabolism
- Abstract
Lipopolysaccharide (LPS) is an endotoxin, a potent stimulator of immune response and induction of LPS leads to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). ARDS is a life-threatening disease worldwide with a high mortality rate. The immunological effect of LPS with spleen and thymus is well documented; however the impact on membrane phospholipid during endotoxemia has not yet been studied. Hence we aimed to investigate the influence of LPS on spleen and thymus phospholipid and fatty acid composition by [(32) P]orthophosphate labeling in rats. The in vitro labeling was carried out with phosphate-free medium (saline). Time course, LPS concentration-dependent, pre- and post-labeling with LPS and fatty acid analysis of phospholipid were performed. Labeling studies showed that 50 µg LPS specifically altered the major phospholipids, phosphatidylcholine and phosphatidylglycerol in spleen and phosphatidylcholine in thymus. Fatty acid analysis showed a marked alteration of unsaturated fatty acids/saturated fatty acids in spleen and thymus leading to immune impairment via the fatty acid remodeling pathway. Our present in vitro lipid metabolic labeling study could open up new vistas for exploring LPS-induced immune impairment in spleen and thymus, as well as the underlying mechanism., (Copyright © 2011 John Wiley & Sons, Ltd.)
- Published
- 2013
- Full Text
- View/download PDF
50. BRCA1 and BRCA2 mutations in the ovarian cancer population across race and ethnicity: special reference to Asia.
- Author
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Shanmughapriya S, Nachiappan V, and Natarajaseenivasan K
- Subjects
- Asia, Europe, Female, Founder Effect, Humans, Ovarian Neoplasms epidemiology, Racial Groups genetics, BRCA1 Protein genetics, BRCA2 Protein genetics, Mutation, Ovarian Neoplasms ethnology, Ovarian Neoplasms genetics
- Abstract
Objective: To evaluate the prevalence and spectrum of BRCA mutations among ovarian carcinoma patients of different races and ethnicity with special reference to Asia., Methods: A systematic review of the literature was undertaken to evaluate the prevalence of BRCA mutations among people belonging to different races. The electronic search strategy was developed specifically for the different databases concerned and via cross-referencing., Results: The frequency of BRCA1 and BRCA2 mutations ranged from 1.1 to 39.7 and from 0 to 13.9, respectively. BRCA1 mutations are more common among ovarian cancer cases than BRCA2 mutations, although the ratio of BRCA1 to BRCA2 varies between populations. The Swedish and Indian populations showed 12 and 7 times as many BRCA1 as BRCA2 mutations, respectively, whilst in a study from Iceland the ratio was 0.5:1. These wide-ranging estimates of the mutation prevalence suggest genetic heterogeneity between different populations., Conclusion: The ability to identify BRCA1/2 mutations was found to be successful in the clinical management of ovarian cancer. Given the implications for clinical care and for advances in cancer prevention, identifying racial difference in genetic or lifestyle factors, which may modify the cancer risk due to BRCA1/2 mutations, is a high priority for future research., (Copyright © 2013 S. Karger AG, Basel.)
- Published
- 2013
- Full Text
- View/download PDF
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