26 results on '"Chia-Yuan Lin"'
Search Results
2. ODP632 Preadmission Use Of Antidiabetic Medications And Mortality Among Patients With Covid-19 Having Type 2 Diabetes: A Meta-analysis
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Nam Nhat Nguyen, Dung S Ho, Hung Song Nguyen, Ngan Ho Khanh Dang, Hung-Yuan Li, Chia-Yuan Lin, Hsiao-Yean Chiu, and Yang-Ching Chen
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Endocrinology, Diabetes and Metabolism - Abstract
Introduction Diabetes is an independent predictor of poor outcomes in patients with COVID-19. We compared the effects of the preadmission use of antidiabetic medications on the in-hospital mortality of patients with COVID-19 having type 2 diabetes. Methods A systematic search was performed until November 30, 2021. We used a random-effects meta-analysis to calculate the pooled OR (95% CI). Results We included 61 studies (3,061,584 individuals). We found some medications protective against COVID-related death, including metformin, GLP-1RA and SGLT-2i. DPP-4i and insulin users were more likely to die during hospitalization. SU, TZD, and AGI were mortality neutral. Metformin use was associated with better outcome in a dose-response manner. Conclusions Metformin, GLP-1RA, and SGLT-2i were associated with lower mortality rate in patients with COVID-19 having type 2 diabetes. DPP-4i and insulin were linked to increased mortality. SU, TZD and AGI were mortality neutral. Presentation: No date and time listed
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- 2022
3. PINK1/parkin-mediated mitophagy pathway is related to neuroprotection by carnosic acid in SH-SY5Y cells
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Chia-Yuan Lin and Chia-Wen Tsai
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Small interfering RNA ,Mitochondrial Diseases ,Ubiquitin-Protein Ligases ,Phosphatase ,PINK1 ,Toxicology ,Parkin ,03 medical and health sciences ,chemistry.chemical_compound ,0404 agricultural biotechnology ,Cell Line, Tumor ,Mitophagy ,Humans ,Tensin ,RNA, Small Interfering ,Oxidopamine ,030304 developmental biology ,Membrane Potential, Mitochondrial ,0303 health sciences ,Chemistry ,Voltage-Dependent Anion Channel 1 ,Cytochromes c ,Carnosic acid ,04 agricultural and veterinary sciences ,General Medicine ,040401 food science ,Mitochondria ,nervous system diseases ,Cell biology ,Neuroprotective Agents ,Abietanes ,Protein Kinases ,VDAC1 ,Food Science - Abstract
Impairment in mitophagy contributes to the pathology of Parkinson's disease. This study investigated whether Phosphatase and tensin homologue (PTEN)-induced kinase 1 (PINK1)/parkin-mediated mitophagy is linked to the protective effect of carnosic acid (CA) from rosemary. Treatment of SH-SY5Y cells with 6-hydroxydopamine (6-OHDA) disrupted the mitochondrial membrane potential, inhibited voltage-dependent anion channel 1 (VDAC1) protein, and induced cytosolic cytochrome c, but CA pretreatment reversed these findings. By immunofluorescence, CA pretreatment was shown to increase the co-localization of red fluorescence (parkin) and MitoTracker green FM fluorescence (mitochondria), indicating that CA promoted the translocation of parkin into mitochondria. Immunoprecipitation with VDAC1 antibody showed that 6-OHDA treatment decreased the interaction of ubiquitinated protein with VDAC1. However, CA pretreatment reversed this reduction in the interaction of ubiquitinated protein with VDAC1. Silencing of PINK1 and parkin by use of small interfering RNA (siRNA) attenuated the ability of CA to reverse 6-OHDA-inhibited autophagic vacuoles. Moreover, in PINK1 siRNA-transfected cells, CA no longer reversed these actions of 6-OHDA on the inhibition of mitophagy-related proteins (PINK1, parkin, VDAC1, and LC3-II) and anti-apoptotic Bcl-2 protein, as well as the induction of apoptotic-related proteins, and nuclear condensation. In conclusion, CA appears to counteract the neurotoxicity of 6-OHDA by activating PINK1/parkin-mediated mitophagy.
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- 2019
4. Preadmission use of antidiabetic medications and mortality among patients with COVID-19 having type 2 diabetes: A meta-analysis
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Nam Nhat Nguyen, Dung Si Ho, Hung Song Nguyen, Dang Khanh Ngan Ho, Hung-Yuan Li, Chia-Yuan Lin, Hsiao-Yean Chiu, and Yang-Ching Chen
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Dipeptidyl-Peptidase IV Inhibitors ,Endocrinology, Diabetes and Metabolism ,Insulins ,Glucagon-Like Peptide-1 Receptor ,Metformin ,COVID-19 Drug Treatment ,Sulfonylurea Compounds ,Endocrinology ,Diabetes Mellitus, Type 2 ,Humans ,Hypoglycemic Agents ,Thiazolidinediones ,Pandemics ,Sodium-Glucose Transporter 2 Inhibitors - Abstract
Diabetes is an independent predictor of poor outcomes in patients with COVID-19. We compared the effects of the preadmission use of antidiabetic medications on the in-hospital mortality of patients with COVID-19 having type 2 diabetes.A systematic search of PubMed, EMBASE, Scopus and Web of Science databases was performed to include studies (except case reports and review articles) published until November 30, 2021. We excluded papers regarding in-hospital use of antidiabetic medications. We used a random-effects meta-analysis to calculate the pooled OR (95% CI) and performed a sensitivity analysis to confirm the robustness of the meta-analyses.We included 61 studies (3,061,584 individuals), which were rated as having low risk of bias. The OR (95% CI) indicated some medications protective against COVID-related death, including metformin [0.54 (0.47-0.62), IMetformin, GLP-1RA, and SGLT-2i were associated with lower mortality rate in patients with COVID-19 having type 2 diabetes. DPP-4i and insulin were linked to increased mortality. Sulfonylurea, thiazolidinedione, and alpha-glucosidase inhibitors were mortality neutral. These findings can have a large impact on the clinicians' decisions amid the COVID-19 pandemic.
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- 2022
5. How to hit that beat: Testing acoustic anchors of rhythmic movement with speech
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Tamara Rathcke and Chia-Yuan Lin
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Rhythm ,Computer science ,Movement (music) ,Speech recognition ,Beat (music) - Published
- 2020
6. Prevention of 4-hydroxynonenal-induced lipolytic activation by carnosic acid is related to the induction of glutathione S-transferase in 3T3-L1 adipocytes
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Chia-Yuan Lin, Yen-Lin Liu, Yun-Hsin Cheng, Chia-Wen Tsai, Chong-Kuei Lii, Wen-Chen Kuo, and Kai-Li Liu
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0301 basic medicine ,medicine.medical_specialty ,Lipolysis ,Cysteine Proteinase Inhibitors ,Fatty Acids, Nonesterified ,Biochemistry ,Antioxidants ,4-Hydroxynonenal ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,3T3-L1 Cells ,Physiology (medical) ,Internal medicine ,Adipocytes ,Cyclic AMP ,medicine ,Animals ,Humans ,Insulin ,Phosphorylation ,Protein kinase A ,Protein kinase B ,Glutathione Transferase ,Aldehydes ,biology ,AMPK ,Carnosic acid ,Enzyme Activation ,Insulin receptor ,030104 developmental biology ,Endocrinology ,chemistry ,030220 oncology & carcinogenesis ,Abietanes ,biology.protein ,Signal Transduction - Abstract
Induction of 4-hydroxynonenal (4-HNE), a major lipid peroxidation aldehyde, is observed in patients with obesity and type 2 diabetes mellitus. The lipolytic response by 4-HNE has been linked to insulin resistance. In this study, we investigated the effects of carnosic acid (CA) on 4-HNE-induced lipolysis and the inhibition of β-oxidation in 3T3-L1 adipocytes. The results indicated that cells pretreated with CA reduced 4-HNE-mediated free fatty acid (FFA) release. Furthermore, CA reversed the inhibition of phosphorylation of Tyr632 of insulin receptor substrate-1 (IRS-1) and Akt and the phosphorylation of Ser307 of IRS-1. CA inhibited 4-HNE-induced phosphorylation of protein kinase A (PKA) and hormone-sensitive lipase (HSL), and reversed the suppression by 4-HNE of phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (p
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- 2018
7. Tapping into linguistic rhythm
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Simone Dalla Bella, Simone Falk, Tamara Rathcke, and Chia-Yuan Lin
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Linguistics and Language ,media_common.quotation_subject ,phonetics, phonology, linguistics, psychology, music, movement sciences ,Metronome ,Language and Linguistics ,law.invention ,Task (project management) ,speech rhythm ,sensorimotor synchronization ,Rhythm ,law ,Vowel ,Perception ,Synchronization (computer science) ,Active listening ,media_common ,Language. Linguistic theory. Comparative grammar ,P101-410 ,Linguistics ,Speech rhythm, sensorimotor synchronization, motor reproduction, vowel onset, p-centre ,Computer Science Applications ,motor reproduction ,Speech rhythm ,vowel onset ,p-centre ,ddc:400 ,Psychology ,Sentence - Abstract
Rhythmic properties of speech and language have been a matter of long-standing debates, with both traditional production and perception studies delivering controversial findings. The present study examines the possibility of investigating linguistic rhythm using movement-based paradigms. Informed by the theory and methods of sensorimotor synchronization, we developed two finger-tapping tasks (synchronization and reproduction), and tested them with English participants. The synchronization task required participants to tap along with the beat of a looped sentence while the reproduction task asked them to tap out the perceived beat patterns after listening to a sentence loop. The results showed that both tasks engaged participants in period tracking of a beat-like structure in the linguistic stimuli, though synchronization did so to a greater extent. Patterns obtained in the reproduction task tended to converge toward participants’ spontaneous tapping rates and showed a degree of regularization. Data collected in the synchronization task displayed a consistent anchoring of taps with the vowel onsets. Overall, synchronization performance with language resembled many well-established findings of sensorimotor synchronization with metronome and music. We conclude that our setting of the sensorimotor synchronization paradigm—finger tapping along with looped spoken phrases—is a valid experimentation tool for studying rhythm perception in language. published
- Published
- 2021
8. Inhibition of JNK by pi class of glutathione S -transferase through PKA/CREB pathway is associated with carnosic acid protection against 6-hydroxydopamine-induced apoptosis
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Chi-Rei Wu, Ruey Hwang Chou, Chia-Wen Tsai, Shu-Wei Chang, Ru Huei Fu, Jing Hsien Chen, and Chia Yuan Lin
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0301 basic medicine ,MAP Kinase Kinase 4 ,Poly ADP ribose polymerase ,Apoptosis ,Toxicology ,CREB ,Cell Line ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Humans ,Enzyme Inhibitors ,Phosphorylation ,RNA, Small Interfering ,Cyclic AMP Response Element-Binding Protein ,Oxidopamine ,Sulfonamides ,Hydroxydopamine ,biology ,Kinase ,Carnosic acid ,General Medicine ,Isoquinolines ,Cyclic AMP-Dependent Protein Kinases ,Molecular biology ,Neuroprotective Agents ,030104 developmental biology ,Glutathione S-transferase ,Glutathione S-Transferase pi ,chemistry ,Abietanes ,biology.protein ,030217 neurology & neurosurgery ,Signal Transduction ,Food Science - Abstract
Pi class of glutathione S-transferase (GST) is known to suppress c-Jun N-terminal kinase (JNK)-related apoptosis through protein-protein interactions. Moreover, signaling by PKA/cAMP response element binding protein (CREB) is necessary for GSTP up-regulation. This study explored whether carnosic acid (CA) from rosemary prevents 6-hydroxydopamine (6-OHDA)-induced neurotoxicity by inhibition of JNK through GSTP via PKA/CREB signaling. Results indicated that the GSTP protein was increased in SH-SY5Y cells treated with CA for 18 and 24 h. However, CA had no significant effect on alpha or mu class of GST. Treatment of CA increased the induction of p-PKAα, nuclear p-CREB, and CRE-DNA binding activity. These effects of CA were attenuated in cells pretreated with the PKA inhibitor H89. CA pretreatment suppressed 6-OHDA-induced apoptosis by inhibition of JNK phosphorylation, poly(ADP)-ribose polymerase cleavage, and nuclear condensation. Pretreatment with H89 and GSTP siRNA attenuated the ability of CA to reverse 6-OHDA-induced apoptosis. By use of immunoprecipitation with JNK antibody to examine the interaction of GSTP-JNK with CA, we showed that CA pretreatment increased the immunoprecipitation of GSTP after 6-OHDA treatment, which suggests that CA promoted the interaction between GSTP and JNK. Conclusion: CA prevents 6-OHDA-induced apoptosis via inhibition of JNK by GSTP through the PKA/CREB pathway.
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- 2017
9. Modulation of ARTS and XIAP by Parkin Is Associated with Carnosic Acid Protects SH-SY5Y Cells against 6-Hydroxydopamine-Induced Apoptosis
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Li Chun Huang, Ru Huei Fu, Chia Yuan Lin, and Chia-Wen Tsai
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0301 basic medicine ,SH-SY5Y ,Ubiquitin-Protein Ligases ,Neuroscience (miscellaneous) ,Apoptosis ,X-Linked Inhibitor of Apoptosis Protein ,Biology ,Inhibitor of apoptosis ,Caspase 7 ,Parkin ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Cell Line, Tumor ,Humans ,Oxidopamine ,Neurons ,Caspase-9 ,Hydroxydopamine ,Ubiquitination ,nervous system diseases ,XIAP ,Neuroprotective Agents ,030104 developmental biology ,Neurology ,Abietanes ,Cancer research ,biology.protein ,Signal transduction ,Septins ,Signal Transduction - Abstract
The mediation of apoptosis-related protein in the TGF-β signaling pathway (ARTS) and X-liked inhibitor of apoptosis protein (XIAP) by parkin plays a critical role in preventing Parkinson's disease. We studied whether carnosic acid (CA) could prevent 6-hydroxydopamine (6-OHDA)-induced apoptosis by modulating ARTS and XIAP through parkin in SH-SY5Y cells. In cells treated with 6-OHDA, the protein expression of ARTS is increased and XIAP is decreased. Pretreatment of cells with CA reversed these effects. Moreover, CA attenuated the activation of caspase 9 and caspase 7 by 6-OHDA. By immunoprecipitation with ARTS antibody, we found that 6-OHDA increased the protein expression of XIAP. However, pretreatment of cells with CA reduced XIAP protein and increased the ubiquitination of ARTS. Silencing of parkin attenuated the ability of CA to reverse the induction of ARTS and apoptotic-related proteins and the reduction of XIAP and parkin protein by 6-OHDA. Similarly, reversal of 6-OHDA-induced nuclear condensation and apoptotic-related proteins by CA was inhibited in cells with XIAP silencing. In conclusion, CA induces parkin by enhancing the ubiquitination of ARTS, leading to induction of XIAP. This may be a novel strategy for preventing Parkinson's disease.
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- 2017
10. Promotion of mitochondrial biogenesis via the regulation of PARIS and PGC-1α by parkin as a mechanism of neuroprotection by carnosic acid
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Ru Huei Fu, Chia-Yuan Lin, Chia-Wen Tsai, Yan-Ning Huang, Tzu-Yu Kuo, and Yu-Hsin Liao
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Small interfering RNA ,Immunoprecipitation ,Ubiquitin-Protein Ligases ,Pharmaceutical Science ,Apoptosis ,Neuroprotection ,Parkin ,Mitochondrial Proteins ,03 medical and health sciences ,0302 clinical medicine ,Ubiquitin ,Cell Line, Tumor ,Drug Discovery ,Humans ,Gene silencing ,RNA, Small Interfering ,Oxidopamine ,030304 developmental biology ,Pharmacology ,0303 health sciences ,Gene knockdown ,Organelle Biogenesis ,biology ,Chemistry ,Dopaminergic Neurons ,Parkinson Disease ,Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ,Mitochondria ,Cell biology ,DNA-Binding Proteins ,Repressor Proteins ,Neuroprotective Agents ,Complementary and alternative medicine ,Mitochondrial biogenesis ,030220 oncology & carcinogenesis ,Abietanes ,biology.protein ,Molecular Medicine ,Transcription Factors - Abstract
Background Impairment of mitochondrial biogenesis is associated with the pathological progression of Parkinson's disease (PD). Parkin-interacting substrate (PARIS) can be ubiquitinated by parkin and prevents the repression of proliferator-activated receptor gamma coactivator-1-alpha (PGC-1α). Purpose This study investigated whether the neuroprotective mechanism of carnosic acid (CA) from rosemary is mediated via the regulation of PARIS and PGC-1α by parkin. Methods The Western blotting and RT-PCR were used to determine protein and mRNA, respectively. To investigate the protein-protein interaction of between PARIS and ubiquitin, the immunoprecipitation assay (IP assay) was utilized. Silencing of endogenous parkin or PGC-1α was performed by using transient transfection of small interfering RNA (siRNA). Results SH-SY5Y cells treated with 6-hydroxydopamine (6-OHDA) increased PARIS protein, decreased PGC-1α protein, and reduced protein and mRNA of mitochondrial biogenesis-related genes. CA pretreatment reversed the effects of 6-OHDA. By IP assay, the interaction of PARIS with ubiquitin protein caused by CA was stronger than that caused by 6-OHDA. Moreover, knockdown of parkin attenuated the ability of CA to reverse the 6-OHDA-induced increase in PARIS and decrease in PGC-1α expression. PGC-1α siRNA was used to investigate how CA influenced the effect of 6-OHDA on the modulation of mitochondrial biogenesis and apoptosis. In the presence of PGC-1α siRNA, CA could no longer significantly reverse the reduction of mitochondrial biogenesis or the induction of cleavage of apoptotic-related proteins by 6-OHDA. Conclusion The cytoprotective of CA is related to the enhancement of mitochondrial biogenesis by inhibiting PARIS and inducing PGC-1α by parkin. The activation of PGC-1α-mediated mitochondrial biogenesis by CA prevents the degeneration of dopaminergic neurons, CA may have therapeutic application in PD.
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- 2021
11. Upregulation of OPA1 by carnosic acid is mediated through induction of IKKγ ubiquitination by parkin and protects against neurotoxicity
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Wen Jiun Chen, Ru Huei Fu, Chia Yuan Lin, and Chia-Wen Tsai
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endocrine system ,Small interfering RNA ,Ubiquitin-Protein Ligases ,Neurotoxins ,Apoptosis ,IκB kinase ,Mitochondrion ,Toxicology ,Mitochondrial Dynamics ,Parkin ,GTP Phosphohydrolases ,03 medical and health sciences ,Mitofusin-2 ,DNM1L ,0404 agricultural biotechnology ,Downregulation and upregulation ,Cell Line, Tumor ,medicine ,Humans ,Oxidopamine ,030304 developmental biology ,0303 health sciences ,Base Sequence ,Chemistry ,Transcription Factor RelA ,Ubiquitination ,04 agricultural and veterinary sciences ,General Medicine ,medicine.disease ,040401 food science ,eye diseases ,I-kappa B Kinase ,Mitochondria ,Up-Regulation ,Cell biology ,Neuroprotective Agents ,Abietanes ,Optic Atrophy 1 ,Food Science - Abstract
An imbalance in mitochondrial dynamics is strongly associated with Parkinson's disease. The fusion protein optic atrophy 1 (OPA1) is up-regulated through the activation of parkin-mediated IκB kinase γ (IKKγ)/p65 signaling. This study investigated whether the neuroprotection of carnosic acid (CA) from rosemary is involved in mitochondrial dynamics and OPA1 protein induction by parkin/IKKγ/p65 signaling. The neurotoxin 6-hydroxydopamine (6-OHDA) treated with SH-SY5Y cells decreased OPA1 and mitofusin 2 fusion proteins, but increased fission 1 and dynamin related protein 1 (DRP1) fission proteins. By immunofluorescence, 6-OHDA induced the fluorescence of green spots outside the mitochondria, indicating that cytochrome c was released to the cytoplasm. Except for the effects on DRP1 protein, CA pretreatment reversed these effects of 6-OHDA. Additionally, CA treatment increased the ubiquitination of IKKγ, nuclear p65 protein, OPA1-p65 DNA binding activity, and OPA1 protein. However, transfection of parkin small interfering RNA (siRNA) attenuated these effects of CA. Furthermore, transfection of OPA1 siRNA abolished the action of CA to reverse 6-OHDA-increased cytosolic cytochrome c protein, apoptotic-related protein cleavage, and cell death. In conclusion, the mechanism by which CA counteracts the toxicity of 6-OHDA is through modulation of mitochondrial dynamics and upregulation of OPA1 via activation of the parkin/IKKγ/p65 pathway.
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- 2020
12. Performance Evaluation of Surrounding Image Display in Smart Glasses Using Image Overlay Method
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Chia-Yuan Lin, Jim-Min Lin, Chih-Ming Lin, Hsien-Chiu Jao, Lan-Lin Chuang, Tin-Tu Wu, and Ming-Fong Tsai
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- 2018
13. The Design of Automatic Bird Data Capture Systems
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Ming-Fong Tsai, Chi-Feng Chen, Yi Chun Lin, Chia-Yuan Lin, and Che-Jui Chang
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0106 biological sciences ,020203 distributed computing ,Social network ,Database ,business.industry ,Computer science ,Automatic identification and data capture ,02 engineering and technology ,computer.software_genre ,010603 evolutionary biology ,01 natural sciences ,Upload ,Filter (video) ,Server ,Computer data storage ,0202 electrical engineering, electronic engineering, information engineering ,business ,computer - Abstract
This paper implements an automatic bird data capture system which uploads data captured from social network websites to the server and stores them in the database. When using the Facebook API to capture data of interest, the system needs to filter the captured data to avoid false data storage. This paper takes building an automatic system that includes reinforcing the training database of the bird community as a top priority.
- Published
- 2018
14. Induction of the pi class of glutathione S-transferase by carnosic acid in rat Clone 9 cells via the p38/Nrf2 pathway
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Chia-Yuan Lin, Chi-Rei Wu, Shu-Wei Chang, Yu-Jung Wang, Jia-Jiuan Wu, and Chia-Wen Tsai
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Pyridines ,NF-E2-Related Factor 2 ,p38 mitogen-activated protein kinases ,Active Transport, Cell Nucleus ,Electrophoretic Mobility Shift Assay ,environment and public health ,Carnosol ,chemistry.chemical_compound ,Genes, Reporter ,Animals ,Anticarcinogenic Agents ,Enzyme Inhibitors ,Gene knockdown ,Membrane Glycoproteins ,biology ,Imidazoles ,Carnosic acid ,General Medicine ,Glutathione ,Molecular biology ,Recombinant Proteins ,Rosmarinus ,Rats ,Clone Cells ,Up-Regulation ,Cytosol ,Enhancer Elements, Genetic ,Glutathione S-transferase ,Glutathione S-Transferase pi ,chemistry ,Enzyme Induction ,Abietanes ,Hepatocytes ,biology.protein ,RNA Interference ,Signal transduction ,Signal Transduction ,Food Science - Abstract
Induction of phase II enzymes is important in cancer chemoprevention. We compared the effect of rosemary diterpenes on the expression of the pi class of glutathione S-transferase (GSTP) in rat liver Clone 9 cells and the signaling pathways involved. Culturing cells with 1, 5, 10, or 20 μM carnosic acid (CA) or carnosol (CS) for 24 h in a dose-dependent manner increased the GSTP expression. CA was more potent than CS. The RNA level and the enzyme activity of GSTP were also enhanced by CA treatment. Treatment with 10 μM CA highly induced the reporter activity of the enhancer element GPEI. Furthermore, CA markedly increased the translocation of nuclear factor erythroid-2 related factor 2 (Nrf2) from the cytosol to the nucleus after 30 to 60 min. CA the stimulated the protein induction of p38, nuclear Nrf2, and GSTP was diminished in the presence of SB203580 (a p38 inhibitor). In addition, SB203580 pretreatment or silencing of Nrf2 by siRNA suppressed the CA-induced GPEI-DNA binding activity and GSTP protein expression. Knockdown of p38 or Nrf2 by siRNA abolished the activation of p38 and Nrf2 as well as the protein induction and enzyme activity of GSTP by CA. These results suggest that CA up-regulates the expression and enzyme activity of GSTP via the p38/Nrf2/GPEI pathway.
- Published
- 2015
15. Carnosic acid protects against 6-hydroxydopamine-induced neurotoxicity in in vivo and in vitro model of Parkinson’s disease: Involvement of antioxidative enzymes induction
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Chi-Rei Wu, Chia-Wen Tsai, Shu-Wei Chang, Chia-Yuan Lin, and Li-Chun Huang
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Male ,Glutamate-Cysteine Ligase ,Poly ADP ribose polymerase ,Blotting, Western ,Caspase 3 ,Motor Activity ,Toxicology ,Thiobarbituric Acid Reactive Substances ,Neuroprotection ,Antioxidants ,Random Allocation ,chemistry.chemical_compound ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Rats, Wistar ,Oxidopamine ,bcl-2-Associated X Protein ,Hydroxydopamine ,Tyrosine hydroxylase ,Plant Extracts ,Superoxide Dismutase ,Neurotoxicity ,Parkinson Disease ,Carnosic acid ,General Medicine ,Glutathione ,medicine.disease ,Molecular biology ,Rats ,Disease Models, Animal ,Glutathione Reductase ,chemistry ,Abietanes ,Poly(ADP-ribose) Polymerases - Abstract
The neuroprotective effects of carnosic acid (CA), a phenolic diterpene isolated from rosemary (Rosmarinus officinalis), have been widely investigated in recent years, however, its protection in in vivo still unclear. In this study, we investigated the behavioral activity and neuroprotective effects of CA in a rat model of Parkinson's disease (PD) induced by 6-hydroxydopamine (6-OHDA). Rats were treated with 20mg/kg body weight of CA for 3 weeks before 6-OHDA exposure. Results indicated that CA improved the locomotor activity and reduced the apomorphine-caused rotation in 6-OHDA-stimulated rats. Significant protection against lipid peroxidation and GSH reduction was observed in the 6-OHDA rats pretreated with CA. Pretreatment with CA increased the protein expression of γ-glutamate-cysteine ligase catalytic subunit, γ-glutamate-cysteine ligase modifier subunit, superoxide dismutase, and glutathione reductase compared with 6-OHDA-stimulated rats and SH-SY5Y cells. Immunoblots showed that the reduction of the Bcl-2/Bax ratio, the induction of caspase 3 cleavage, and the induction of poly(ADP-ribose) polymerase (PARP) cleavage by 6-OHDA was reversed in the presence of SB203580 (a p38 inhibitor) or SP600125 (a JNK inhibitor) in SH-SY5Y cells. Rats treated with CA reversed the 6-OHDA-mediated the activation of c-Jun NH2-terminal kinase and p38, the down-regulation of the Bcl-2/Bax ratio, the up-regulation of cleaved caspase 3/caspase 3 and cleaved PARP/PARP ratio, and the down-regulation of tyrosine hydroxylase protein. However, BAM7, an activator of Bax, attenuated the effect of CA on apoptosis in SH-SY5Y cells. These results suggest that CA protected against 6-OHDA-induced neurotoxicity is attributable to its anti-apoptotic and anti-oxidative action. The present findings may help to clarify the possible mechanisms of rosemary in the neuroprotection of PD.
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- 2015
16. EZH2 in Cancer Progression and Potential Application in Cancer Therapy: A Friend or Foe?
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Cheng Ming Peng, Tan Wei Liao, Wing P. Chan, Ruey Hwang Chou, Ke Sin Yan, Yi-Jui Liu, Shou Chun Lee, and Chia Yuan Lin
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0301 basic medicine ,lncRNAs ,macromolecular substances ,Review ,Catalysis ,epigenetic regulation ,lcsh:Chemistry ,Inorganic Chemistry ,03 medical and health sciences ,Histone H3 ,Neoplasms ,medicine ,Humans ,cancer ,Enhancer of Zeste Homolog 2 Protein ,Epigenetics ,Cancer epigenetics ,EZH2 ,Physical and Theoretical Chemistry ,Enzyme Inhibitors ,lcsh:QH301-705.5 ,Molecular Biology ,Spectroscopy ,Regulation of gene expression ,biology ,Tumor Suppressor Proteins ,Organic Chemistry ,Cancer ,General Medicine ,medicine.disease ,Computer Science Applications ,microRNAs ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Histone ,lcsh:Biology (General) ,lcsh:QD1-999 ,Histone methyltransferase ,Mutation ,EZH2 inhibitors ,biology.protein ,Cancer research ,Disease Progression ,RNA, Long Noncoding - Abstract
Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, catalyzes tri-methylation of histone H3 at Lys 27 (H3K27me3) to regulate gene expression through epigenetic machinery. EZH2 functions as a double-facet molecule in regulation of gene expression via repression or activation mechanisms, depending on the different cellular contexts. EZH2 interacts with both histone and non-histone proteins to modulate diverse physiological functions including cancer progression and malignancy. In this review article, we focused on the updated information regarding microRNAs (miRNAs) and long non coding RNAs (lncRNAs) in regulation of EZH2, the oncogenic and tumor suppressive roles of EZH2 in cancer progression and malignancy, as well as current pre-clinical and clinical trials of EZH2 inhibitors.
- Published
- 2017
17. Carnosic Acid Attenuates 6-Hydroxydopamine-Induced Neurotoxicity in SH-SY5Y Cells by Inducing Autophagy Through an Enhanced Interaction of Parkin and Beclin1
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Chia-Yuan Lin and Chia-Wen Tsai
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0301 basic medicine ,SH-SY5Y ,Ubiquitin-Protein Ligases ,Neurotoxins ,Neuroscience (miscellaneous) ,Caspase 3 ,Apoptosis ,Biology ,Neuroprotection ,Parkin ,Wortmannin ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,0302 clinical medicine ,Cell Line, Tumor ,Autophagy ,Humans ,Phosphorylation ,RNA, Small Interfering ,Oxidopamine ,TOR Serine-Threonine Kinases ,Carnosic acid ,Transfection ,nervous system diseases ,Cell biology ,Androstadienes ,030104 developmental biology ,Neuroprotective Agents ,Neurology ,chemistry ,Biochemistry ,Abietanes ,Vacuoles ,Beclin-1 ,Macrolides ,030217 neurology & neurosurgery ,Biomarkers ,Protein Binding - Abstract
Enhanced removal of abnormal protein aggregates or injured organelles through autophagy is related to neuroprotection in Parkinson's disease. In this study, we explored whether the induction of autophagy is associated with the neuroprotection of rosemary carnosic acid (CA) against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in SH-SY5Y cells. The results indicated that cells treated with CA had increased protein levels of parkin and autophagy-related markers, including phosphatidylinositol 3-kinase p100, Beclin1, autophagy-related gene 7, and microtubule-associated protein 1 light chain 3-II, as well as enhanced formation of autophagic vacuoles. Treatment of cells with 6-OHDA decreased the levels of parkin and the autophagy markers, but CA pretreatment reversed these effects. However, wortmannin (an autophagosome formation blocker) pretreatment attenuated the effect of CA. After CA pretreatment, the induction of cleaved caspase 3, cleaved poly-ADP ribose polymerase, and nuclear condensation by 6-OHDA were alleviated. Both wortmannin and bafilomycin A1 (an autophagosome-lysosome fusion blocker) inhibited the anti-apoptosis effects of CA. Additionally, we performed immunoprecipitation with anti-parkin antibody and found that the interaction of parkin and Beclin1 protein was reduced by 6-OHDA but that this effect was reversed in cells pretreated with CA. Moreover, transfection of parkin siRNA in cells inhibited the ability of CA to alleviate 6-OHDA-decreased autophagy-related markers and nuclear condensation. In conclusion, CA protects against 6-OHDA-induced apoptosis by inducing autophagy through the interaction of parkin and Beclin1. These results provide a future strategy for use of CA in the prevention of Parkinson's disease.
- Published
- 2016
18. Carnosic acid protects SH-SY5Y cells against 6-hydroxydopamine-induced cell death through upregulation of parkin pathway
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Chia-Yuan Lin and Chia-Wen Tsai
- Subjects
0301 basic medicine ,Male ,SH-SY5Y ,Ubiquitin-Protein Ligases ,Caspase 3 ,PINK1 ,Biology ,Parkin ,Antioxidants ,Animals, Genetically Modified ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,0302 clinical medicine ,Downregulation and upregulation ,Cell Line, Tumor ,MG132 ,medicine ,Animals ,Humans ,Rats, Wistar ,Caenorhabditis elegans ,Oxidopamine ,Pharmacology ,Cell Death ,Carnosic acid ,Molecular biology ,nervous system diseases ,Rats ,Up-Regulation ,030104 developmental biology ,chemistry ,Cytoprotection ,Abietanes ,Proteasome inhibitor ,alpha-Synuclein ,030217 neurology & neurosurgery ,medicine.drug ,Signal Transduction - Abstract
Parkin is a Parkinson's disease (PD)-linked gene that plays an important role in the ubiquitin-proteasome system (UPS). This study explored whether carnosic acid (CA) from rosemary protects against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity via upregulation of parkin in vivo and in vitro. We found that the reduction in proteasomal activity by 6-OHDA was attenuated in SH-SY5Y cells pretreated with 1 μM CA. Immunoblots showed that CA reversed the induction of ubiquitinated protein and the reduction of PTEN-induced putative kinase 1 (PINK1) and parkin protein in 6-OHDA-treated SH-SY5Y cells and rats. Moreover, in a transgenic OW13 Caenorhabditis elegans model of PD that expresses human α-synuclein in muscle cells, CA reduced α-synuclein accumulation in a dose-dependent manner. In cells pretreated with the proteasome inhibitor MG132, CA no longer reversed the 6-OHDA-mediated induction of cleavage of caspase 3 and poly(ADP)-ribose polymerase and no longer reversed the suppression of proteasome activity. When parkin expression was silenced by use of small interfering RNA, the ability of CA to inhibit apoptosis and induce proteasomal activity was significantly reduced. The reduction in 6-OHDA-induced neurotoxicity by CA was associated with the induction of parkin, which in turn upregulated the UPS and then decreased cell death.
- Published
- 2015
19. Carnosic Acid, a Rosemary Phenolic Compound, Induces Apoptosis Through Reactive Oxygen Species-Mediated p38 Activation in Human Neuroblastoma IMR-32 Cells
- Author
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Jing-Hsien Chen, Chia-Yuan Lin, Chia-Wen Tsai, and Hui-Hsuan Lin
- Subjects
MAPK/ERK pathway ,p38 mitogen-activated protein kinases ,Apoptosis ,Biology ,p38 Mitogen-Activated Protein Kinases ,Biochemistry ,Neuroblastoma ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Cell Line, Tumor ,Humans ,Viability assay ,Extracellular Signal-Regulated MAP Kinases ,Protein kinase A ,chemistry.chemical_classification ,Reactive oxygen species ,Caspase 3 ,Plant Extracts ,Kinase ,JNK Mitogen-Activated Protein Kinases ,Carnosic acid ,General Medicine ,Molecular biology ,Acetylcysteine ,Cell biology ,Enzyme Activation ,Proto-Oncogene Proteins c-bcl-2 ,chemistry ,Abietanes ,Reactive Oxygen Species - Abstract
Carnosic acid (CA), a rosemary phenolic compound, has been shown to display anti-cancer activity. We examined the apoptotic effect of CA in human neuroblastoma IMR-32 cells and elucidated the role of the reactive oxygen species (ROS) and mitogen-activated protein kinase (MAPK) associated with carcinogenesis. The result indicated that CA decreased the cell viability in a dose-dependent manner. Further investigation in IMR-32 cells revealed that cell apoptosis following CA treatment is the mechanism as confirmed by flow cytometry, hoechst 33258, and caspase-3/-9 and poly(ADP-ribose) polymerase (PARP) activation. Immunoblotting suggested a down-regulation of anti-apoptotic Bcl-2 protein in the CA-treated cells. In flow cytometric analysis, CA caused the generation of reactive oxygen species (ROS); however, pretreatment with the antioxidant N-acetylcysteine (NAC) attenuated the CA-induced generation of ROS and apoptosis. This effect was accompanied by increased activation of p38 and by decreased activation of extracellular signal-regulated kinase (ERK) as well as activation of c-Jun NH(2)-terminal kinase (JNK). Moreover, NAC attenuated the CA-induced phosphorylation of p38. Silencing of p38 by siRNA gene knockdown reduced the CA-induced activation of caspase-3. In conclusion, ROS-mediated p38 MAPK activation plays a critical role in CA-induced apoptosis in IMR-32 cells.
- Published
- 2011
20. Structure and Function Relationship Study of Allium Organosulfur Compounds on Upregulating the Pi Class of Glutathione S-Transferase Expression
- Author
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Chia-Yuan Lin, Chia-Wen Tsai, Haw-Wen Chen, Chong-Kuei Lii, and Kai-Li Liu
- Subjects
Sulfides ,Allium ,Cell Line ,Structure-Activity Relationship ,chemistry.chemical_compound ,Pi ,Animals ,RNA, Messenger ,Glutathione Transferase ,chemistry.chemical_classification ,Sulfur Compounds ,biology ,Chemistry ,Diallyl disulfide ,c-jun ,General Chemistry ,Glutathione ,Enzyme assay ,Rats ,Up-Regulation ,Enzyme ,Glutathione S-transferase ,Liver ,Biochemistry ,biology.protein ,General Agricultural and Biological Sciences ,Organosulfur compounds - Abstract
Allium organosulfides are potential chemopreventive compounds due to their effectiveness on the induction of phase II detoxification enzyme expression. In this study, we examined the structure and function relationship among various alk(en)yl sulfides on the expression of the pi class of glutathione S-transferase (GSTP) in rat Clone 9 cells, and what mechanism is involved. Cells were treated with 300 μM dipropyl sulfide (DPS), dipropyl disulfide (DPDS), propyl methyl sulfide (PMS), and propyl methyl disulfide (PMDS) for 48 h. DPDS and PMDS displayed more potency on GSTP protein and mRNA induction than that of DPS and PMS. Next, we compared the effectiveness of DPDS, PMDS, and diallyl disulfide (DADS), which have the same number of sulfur atoms but differ in the side alk(en)yl groups. The maximum increases on protein expression, mRNA level, and enzyme activity were noted in cells treated with DADS, followed by DPDS and PMDS. A reporter assay showed that three disulfides increased GSTP enhancer I (GPE I) activity (P0.05) in the order DADSDPDS ≥ PMDS. Electromobility gel shift assays showed that the DNA binding of GPE I to nuclear proteins reached a maximum at 1 to 3 h after alk(en)yl disulfide treatment. Supershift assay revealed that c-jun bound to GPE I. Silencing of extracellular signal-regulated kinase (ERK) 2 expression inhibited c-jun activation and GSTP induction. Results suggest that both the type of alk(en)yl groups and number of sulfur atoms are determining factors of allium organosulfides on inducing GSTP expression, and it is likely related to the ERK-c-Jun-GPE I pathway.
- Published
- 2011
21. Carnosic acid attenuated 6-hydroxydopamine-induced apoptosis through mediation of the mitochondrial biogenesis by parkin in SH-SY5Y cells
- Author
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Chia-Wen Tsai, Chia-Yuan Lin, and Yan-Ning Huang
- Subjects
Hydroxydopamine ,chemistry.chemical_compound ,SH-SY5Y ,Mitochondrial biogenesis ,Chemistry ,Apoptosis ,Applied Mathematics ,General Mathematics ,Mediation ,Carnosic acid ,Parkin ,Cell biology - Published
- 2018
22. Inhibition of 12-lipoxygenase during baicalein-induced human lung nonsmall carcinoma H460 cell apoptosis
- Author
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Henry W.-C. Leung, M.-Y. Lai, Hong-Zin Lee, W.H. Yang, and Chia-Yuan Lin
- Subjects
Programmed cell death ,Lung Neoplasms ,Blotting, Western ,Cell ,Apoptosis ,Biology ,Toxicology ,chemistry.chemical_compound ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,medicine ,Humans ,Lipoxygenase Inhibitors ,Fragmentation (cell biology) ,DNA Primers ,Cyclin-dependent kinase 1 ,Reverse Transcriptase Polymerase Chain Reaction ,General Medicine ,Cell cycle ,Flow Cytometry ,Apoptotic body ,Antineoplastic Agents, Phytogenic ,respiratory tract diseases ,Baicalein ,medicine.anatomical_structure ,chemistry ,Biochemistry ,Flavanones ,Cancer research ,RNA ,Phytotherapy ,Scutellaria baicalensis ,Food Science - Abstract
Baicalein is known as a 12-lipoxygenase (12-LOX) inhibitor. The 12-LOX is found to be involved in the progression of human cancers and the inhibitor of 12-LOX offers a target for the prevention cancer. We demonstrated the inhibitory effect of baicalein on the gene and protein expression of 12-LOX in H460 human lung nonsmall carcinoma cell line. Treatment of baicalein inhibited the growth of H460 cells in a dose-dependent manner. Following 24 h exposure to 50 μM baicalein, cell cycle analysis revealed an increase in the cell population in S-phase. During the S-phase arrest, baicalein decreased the protein levels of cdk1 and cyclin B1, which are the regulating proteins of S-phase transition to G2/M-phase, in this study. Furthermore, baicalein induced the most of H460 cell apoptosis after treatment for 48 h. H460 cells formed vesicles and apoptotic body, and then floated after treatment with baicalein. Baicalein-induced H460 cell apoptosis was confirmed by DNA condensation and fragmentation. Baicalein-induced apoptosis were also accompanied by decreasing in Bcl-2 and proform of caspase-3 and increasing p53 and Bax protein levels. Pretreatment with a specific caspase-3 inhibitor, Ac-DEVD-CHO, partially reduced baicalein-induced cell death, indicating baicalein induces apoptosis is partially dependent on caspase-3 pathway in H460 cells. These data suggest that baicalein, a 12-LOX inhibitor, inhibits the proliferation of H460 cells via S-phase arrest and induces apoptosis in association with the regulation of molecules in the cell cycle and apoptosis-related proteins.
- Published
- 2007
23. Induction of Pi form of glutathione S-transferase by carnosic acid is mediated through PI3K/Akt/NF-κB pathway and protects against neurotoxicity
- Author
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Jing Hsien Chen, Ru Huei Fu, Chia-Wen Tsai, and Chia Yuan Lin
- Subjects
Male ,Cell Survival ,Blotting, Western ,Electrophoretic Mobility Shift Assay ,IκB kinase ,Toxicology ,Transfection ,chemistry.chemical_compound ,Phosphatidylinositol 3-Kinases ,Cell Line, Tumor ,Animals ,Humans ,Enzyme inducer ,Rats, Wistar ,Oxidopamine ,Protein kinase B ,PI3K/AKT/mTOR pathway ,biology ,Dose-Response Relationship, Drug ,Kinase ,Plant Extracts ,NF-kappa B ,Carnosic acid ,General Medicine ,Molecular biology ,IκBα ,Glutathione S-transferase ,Neuroprotective Agents ,chemistry ,Glutathione S-Transferase pi ,Enzyme Induction ,Abietanes ,biology.protein ,Neurotoxicity Syndromes ,Proto-Oncogene Proteins c-akt ,Signal Transduction - Abstract
Carnosic acid (CA), a diterpene found in the rosemary (Rosmarinus officinalis), has been reported to have a neuroprotective effect. Glutathione S-transferase (GST) P (GSTP) is a phase II detoxifying enzyme that provides a neuroprotective effect. The aim of this study was to explore whether the neuroprotective effect of CA is via an upregulation of GSTP expression and the possible signaling pathways involved. SH-SY5Y cells were pretreated with 1 μM CA followed by treatment with 100 μM 6-hydroxydopamine (6-OHDA). Both immunoblotting and enzyme activity results show that CA also induced protein expression and enzyme activity of GSTP. Moreover, CA significantly increased the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/Akt, the nuclear translocation of p65, but not mitogen-activated protein kinases (p < 0.05). Pretreatment with LY294002 (a PI3K/Akt inhibitor) suppressed the CA-induced phosphorylation of IκB kinase (IKK) and IκBα, p65 nuclear translocation, and nuclear factor-kappa B (NF-κB)-DNA binding activity as well as GSTP protein expression. Furthermore, CA attenuated 6-OHDA-induced caspase 3 activation, and cell death was reversed by GSTP siRNA or LY294002 treatment. Additionally, male Wistar rats with lesions induced by 6-OHDA treatment in the right striatum responded to treatment with CA, which significantly reversed the reduction in GSTP protein expression that resulted from lesioning. We suggest that CA prevents 6-OHDA-induced apoptosis through an increase in GSTP expression via activation of the PI3K/Akt/NF-κB pathway. Therefore, CA may be a promising candidate for use in the prevention of Parkinson's disease.
- Published
- 2014
24. Carnosic acid prevents 6-hydroxydopamine-induced cell death in SH-SY5Y cells via mediation of glutathione synthesis
- Author
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Chia-Wen Tsai, Fung-Ju Lin, Hsin-Ping Ou, Chia-Yuan Lin, Chi-Rei Wu, Jing-Hsien Chen, and Shu-Wei Chang
- Subjects
Programmed cell death ,SH-SY5Y ,NF-E2-Related Factor 2 ,p38 mitogen-activated protein kinases ,Glutamate-Cysteine Ligase ,Down-Regulation ,Tetrazolium Salts ,Apoptosis ,Pharmacology ,Toxicology ,Neuroprotection ,p38 Mitogen-Activated Protein Kinases ,Antioxidants ,Cell Line ,chemistry.chemical_compound ,Humans ,Oxidopamine ,Buthionine Sulfoximine ,Hydroxydopamine ,Plant Extracts ,JNK Mitogen-Activated Protein Kinases ,Carnosic acid ,General Medicine ,Glutathione ,Thiazoles ,chemistry ,Biochemistry ,Abietanes ,Reactive Oxygen Species ,Signal Transduction - Abstract
Understanding the neuroprotective effects of the rosemary phenolic diterpene carnosic acid (CA) has attracted increasing attention. We explored the mechanism by which CA modulates the neurotoxic effects of 6-hydroxydopamine (6-OHDA) in SH-SY5Y cells. Cells were pretreated with CA for 12 h followed by treatment with 100 μM 6-OHDA for 12 or 24 h. Cell viability determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolim bromide (MTT) assay indicated that 0.1 to 1 μM CA dose-dependently attenuated the cell death induced by 6-OHDA, whereas the effect of 3-5 μM CA was weaker. CA at 1 μM suppressed the 6-OHDA-induced nuclear condensation, reactive oxygen species generation, and cleavage of caspase 3 and PARP. Immunoblots showed that the phosphorylation of c-Jun NH(2)-terminal kinase (JNK) and p38 by 6-OHDA was reduced in the presence of CA. Incubation of cells with CA resulted in significant increases in the total glutathione (GSH) level and the protein expression of the γ-glutamylcysteine ligase catalytic subunit and modifier subunit. L-Buthionine-sulfoximine, an inhibitor of GSH synthesis, attenuated the effect of CA on cell death and apoptosis. Treatment with CA also led to an increase in nuclear factor erythroid-2 related factor 2 (Nrf2) activation, antioxidant response element (ARE)-luciferase reporter activity, and DNA binding to the ARE. Silencing of Nrf2 expression alleviated the reversal of p38 and JNK1/2 activation by CA. These results suggest that the attenuation of 6-OHDA-induced apoptosis by CA is associated with the Nrf2-driven synthesis of GSH, which in turn down-regulates the JNK and p38 signaling pathways. The CA compound may be a promising candidate for neuroprotection in Parkinson's disease.
- Published
- 2012
25. Carnosic acid induces the NAD(P)H: quinone oxidoreductase 1 expression in rat clone 9 cells through the p38/nuclear factor erythroid-2 related factor 2 pathway
- Author
-
Chia-Yuan Lin, Yu-Jung Wang, and Chia-Wen Tsai
- Subjects
Transcription, Genetic ,NF-E2-Related Factor 2 ,Blotting, Western ,Medicine (miscellaneous) ,Response Elements ,Transfection ,p38 Mitogen-Activated Protein Kinases ,Carnosol ,Antioxidants ,chemistry.chemical_compound ,NAD(P)H Dehydrogenase (Quinone) ,Animals ,Anticarcinogenic Agents ,Gene Silencing ,RNA, Messenger ,Phosphorylation ,Luciferases ,Cells, Cultured ,chemistry.chemical_classification ,Cell Nucleus ,Nutrition and Dietetics ,biology ,Dose-Response Relationship, Drug ,Plant Extracts ,Carnosic acid ,Molecular biology ,Enzyme assay ,Rats ,Up-Regulation ,Enzyme ,chemistry ,Biochemistry ,Liver ,Abietanes ,biology.protein ,NAD+ kinase ,Signal transduction ,Plasmids ,Signal Transduction - Abstract
The anticarcinogenic effect of rosemary has been partly attributed to the modulation of the activity and expression of phase II detoxification enzymes. Here we compared the effects of phenolic diterpenes from rosemary on the expression of NAD(P)H: quinone oxidoreductase 1 (NQO1) in rat Clone 9 liver cells. Cells were treated with 1‐20 mmol/L of carnosic acid (CA) or carnosol (CS) for 24 h. Both CA and CS dose dependently increased NQO1 enzyme activity and protein expression, and the induction potency of CA was stronger than that of CS. The increase in NQO1 enzyme activity in cells treated with 10 mmol/L CA and CS was 4.1- and 1.9-fold, respectively (P , 0.05). RT-PCR showed that CA and CS induced NQO1 mRNA in a dose-dependent manner. Furthermore, CA dose dependently induced transcription of nuclear factor erythroid-2 related factor 2 (Nrf2) and antioxidant response element (ARE)-luciferase reporter activity. Silencing of Nrf2 expression alleviated NQO1 protein expression and ARE-luciferase activity by CA. Moreover, the phosphorylation of p38 was mainly stimulated in the presence of CA. Pretreatment with SB203580 or silencing of p38 expression inhibited Nrf2 activation and NQO1 induction. These results suggest that the increased NQO1 expression by CA is likely related to the p38-Nrf2 pathway and help to clarify the possible molecular mechanism of action of rosemary phenolic compounds in drug metabolism and cancer prevention. J. Nutr. doi: 10.3945/jn.111.146779.
- Published
- 2011
26. Kaempferol induces apoptosis in human lung non-small carcinoma cells accompanied by an induction of antioxidant enzymes
- Author
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Wen-Hui Yang, Hong-Zin Lee, M.-Y. Wang, Mann-Jen Hour, Henry W.-C. Leung, and Chia-Yuan Lin
- Subjects
Programmed cell death ,Antioxidant ,Lung Neoplasms ,Tumor suppressor gene ,Cell Survival ,medicine.medical_treatment ,Blotting, Western ,Apoptosis ,Biology ,Toxicology ,Antioxidants ,Membrane Potentials ,chemistry.chemical_compound ,Adenosine Triphosphate ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,medicine ,Humans ,DAPI ,Kaempferols ,L-Lactate Dehydrogenase ,Caspase 3 ,Apoptosis Inducing Factor ,General Medicine ,Free Radical Scavengers ,Flow Cytometry ,Antineoplastic Agents, Phytogenic ,Immunohistochemistry ,Acetylcysteine ,Mitochondria ,Neoplasm Proteins ,Biochemistry ,chemistry ,Enzyme Induction ,Cancer research ,Apoptosis-inducing factor ,Kaempferol ,Reactive Oxygen Species ,Intracellular ,Food Science - Abstract
Kaempferol (3, 4',5,7-tetrahydroxyflavone) is one of the most commonly found dietary flavonols. The biological and pharmacological effects of kaempferol may depend upon its behavior as either an antioxidant or a prooxidant. However, the clear biological effects of prooxidant or antioxidant character of kaempferol has not been clarified yet. The overall objective of the present study is to explore the role of prooxidant or antioxidant in kaempferol-induced cell toxicity. In this paper, we have proved that antioxidant pathway may be involved in kaempferol induces H460 cell apoptosis. Kaempferol-induced H460 cell apoptosis is a typical apoptosis that was accompanied by a significant DNA condensation and increasing intracellular ATP levels. Kaempferol-induced apoptosis is related to its ability to change the expression of apoptotic markers, such as caspase-3 (caspase-dependent) and AIF (caspase-independent). The overexpression of antioxidant enzyme Mn SOD protein levels, which was promoted to a new type tumor suppressor gene in several human cancer cells recently, may be an important role in kaempferol-induced H460 cell apoptosis.
- Published
- 2005
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