Search

Oxidative stress, characterized by an imbalance between the production of reactive oxygen species (ROS) and the cellular anti-oxidant defense mechanisms, plays a critical role in the pathogenesis of various human diseases. Redox metabolism, comprising a network of enzymes and genes, serves as a crucial regulator of ROS levels and maintains cellular homeostasis. This review provides an overview of the most important human genes encoding for proteins involved in ROS generation, ROS detoxification, and production of reduced nicotinamide adenine dinucleotide phosphate (NADPH), and the genetic disorders that lead to dysregulation of these vital processes. Insights gained from studies on inherited monogenic metabolic diseases provide valuable basic understanding of redox metabolism and signaling, and they also help to unravel the underlying pathomechanisms that contribute to prevalent chronic disorders like cardiovascular disease, neurodegeneration, and cancer. [ABSTRACT FROM AUTHOR]

Oxidative stress, characterized by an imbalance between the production of reactive oxygen species (ROS) and the cellular anti-oxidant defense mechanisms, plays a critical role in the pathogenesis of various human diseases. Redox metabolism, comprising a network of enzymes and genes, serves as a crucial regulator of ROS levels and maintains cellular homeostasis. This review provides an overview of the most important human genes encoding for proteins involved in ROS generation, ROS detoxification, and production of reduced nicotinamide adenine dinucleotide phosphate (NADPH), and the genetic disorders that lead to dysregulation of these vital processes. Insights gained from studies on inherited monogenic metabolic diseases provide valuable basic understanding of redox metabolism and signaling, and they also help to unravel the underlying pathomechanisms that contribute to prevalent chronic disorders like cardiovascular disease, neurodegeneration, and cancer.

Drug resistance is the main obstacle to achieving a cure in many cancer patients. Reactive oxygen species (ROS) are master regulators of cancer development that act through complex mechanisms. Remarkably, ROS levels and antioxidant content are typically higher in drug-resistant cancer cells than in non-resistant and normal cells, and have been shown to play a central role in modulating drug resistance. Therefore, determining the underlying functions of ROS in the modulation of drug resistance will contribute to develop therapies that sensitize cancer resistant cells by leveraging ROS modulation. In this review, we summarize the notable literature on the sources and regulation of ROS production and highlight the complex roles of ROS in cancer chemoresistance, encompassing transcription factor–mediated chemoresistance, maintenance of cancer stem cells, and their impact on the tumor microenvironment. We also discuss the potential of ROS-targeted therapies in overcoming tumor therapeutic resistance.

Bioactive compounds (BCs) are known to exhibit antioxidant, anti-inflammatory, and anti-cancer properties by regulating the cellular redox balance and histone acetylation state. BCs can control chronic oxidative states caused by dietary stress, i.e., alcohol, high-fat, or high-glycemic diet, and adjust the redox balance to recover physiological conditions. Unique functions of BCs to scavenge reactive oxygen species (ROS) can resolve the redox imbalance due to the excessive generation of ROS. The ability of BCs to regulate the histone acetylation state contributes to the activation of transcription factors involved in immunity and metabolism against dietary stress. The protective properties of BCs are mainly ascribed to the roles of sirtuin 1 (SIRT1) and nuclear factor erythroid 2–related factor 2 (NRF2). As a histone deacetylase (HDAC), SIRT1 modulates the cellular redox balance and histone acetylation state by mediating ROS generation, regulating nicotinamide adenine dinucleotide (NAD+)/NADH ratio, and activating NRF2 in metabolic progression. In this study, the unique functions of BCs against diet-induced inflammation, oxidative stress, and metabolic dysfunction have been considered by focusing on the cellular redox balance and histone acetylation state. This work may provide evidence for the development of effective therapeutic agents from BCs. [ABSTRACT FROM AUTHOR]

Bioactive compounds (BCs) are known to exhibit antioxidant, anti-inflammatory, and anti-cancer properties by regulating the cellular redox balance and histone acetylation state. BCs can control chronic oxidative states caused by dietary stress, i.e., alcohol, high-fat, or high-glycemic diet, and adjust the redox balance to recover physiological conditions. Unique functions of BCs to scavenge reactive oxygen species (ROS) can resolve the redox imbalance due to the excessive generation of ROS. The ability of BCs to regulate the histone acetylation state contributes to the activation of transcription factors involved in immunity and metabolism against dietary stress. The protective properties of BCs are mainly ascribed to the roles of sirtuin 1 (SIRT1) and nuclear factor erythroid 2–related factor 2 (NRF2). As a histone deacetylase (HDAC), SIRT1 modulates the cellular redox balance and histone acetylation state by mediating ROS generation, regulating nicotinamide adenine dinucleotide (NAD+)/NADH ratio, and activating NRF2 in metabolic progression. In this study, the unique functions of BCs against diet-induced inflammation, oxidative stress, and metabolic dysfunction have been considered by focusing on the cellular redox balance and histone acetylation state. This work may provide evidence for the development of effective therapeutic agents from BCs.

Levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in cells and cell redox balance are of great interest in live cells as they are correlated to several pathological and physiological conditions of living cells. ROS and RNS detection is limited due to their spatially restricted abundance: they are usually located in sub-cellular areas (e.g., in specific organelles) at low concentration. In this work, we will review and highlight the electrochemical approach to this bio-analytical issue. Combining electrochemical methods and miniaturization strategies, specific, highly sensitive, time, and spatially resolved measurements of cellular oxidative stress and redox balance analysis are possible. [ABSTRACT FROM AUTHOR]

Aim: Preparation of a herbometallic nano-drug, Rasa Manikya nanoparticle (RMNP) and investigation of its antimicrobial, and anticancer activity. Materials & methods: Physicochemical characterizations of RMNP were performed using different analytical methods. The antimicrobial and anticancer potential of RMNPs were assessed by an in vitro cellular assay. Bacterial cell wall lysis was observed by field emission scanning electron microscopy and mitochondrial metabolism alteration factor was measured via standard method. Results: Physicochemical analysis confirmed that RMNP was rich in mineral constituents. Synergistic effect of RMNPs enhanced lysis of bacterial peptidoglycan layers and impaired cellular redox balance, GSH/NADPH level followed by induction of cell apoptosis. Conclusion: The present study confirms that RMNP can be used as a dual therapeutic option for combating drug-resistant microbial strains and breast cancer. [ABSTRACT FROM AUTHOR]

Drug resistance is the main obstacle to achieving a cure in many cancer patients. Reactive oxygen species (ROS) are master regulators of cancer development that act through complex mechanisms. Remarkably, ROS levels and antioxidant content are typically higher in drug-resistant cancer cells than in non-resistant and normal cells, and have been shown to play a central role in modulating drug resistance. Therefore, determining the underlying functions of ROS in the modulation of drug resistance will contribute to develop therapies that sensitize cancer resistant cells by leveraging ROS modulation. In this review, we summarize the notable literature on the sources and regulation of ROS production and highlight the complex roles of ROS in cancer chemoresistance, encompassing transcription factor–mediated chemoresistance, maintenance of cancer stem cells, and their impact on the tumor microenvironment. We also discuss the potential of ROS-targeted therapies in overcoming tumor therapeutic resistance. [Display omitted] • Redox regulation in tumor cells participated in the promotion of chemoresistance. • Many clinical trials targeting ROS modulators are ongoing, mostly phase I or II. • ROS modulates chemoresistance of tumor by impacting TFs, CSCs and TME. [ABSTRACT FROM AUTHOR]

Abstract: 13-Hydroxy-15-oxo-zoapatlin (OZ), a nor-kaurane diterpene, was first described as a compound inhibiting the proliferation of human cancer cell lines. Successively, it was reported that OZ inhibits the G2 DNA damage checkpoint and causes mitotic arrest. To get more insight into the molecular mechanism(s) underlying the antitumor potential of OZ, we evaluated the proapoptotic activity of this molecule. OZ was found to induce hypodiploidia and phosphatidylserine externalization, two hallmarks of apoptosis; to disrupt mitochondrial membrane potential; and to trigger caspase-3 activation. OZ-induced cell death, mostly dependent upon the presence of the α,β-carbonyl group, is strongly related to alterations in the cellular redox balance. The interaction of OZ with cellular components and proteins containing reactive thiols was evaluated by mass spectrometry-based approaches. A specific reactivity of this compound toward glutathione and thioredoxin was observed. [Copyright &y& Elsevier]

Membrane lipid peroxidation processes yield products that may react with DNA and proteins to cause oxidative modifications. In the present study, we evaluated lipid peroxidation-mediated cytotoxicity and oxidative DNA damage in U937 cells. Upon exposure of U937 cells to tert-butylhydroperoxide (t-BOOH) and 2,2′-azobis (2-amidinopropane) hydrochloride (AAPH), which induce lipid peroxidation in membranes, the cells exhibited a reduction in viability and an increase in the endogenous production of reactive oxygen species (ROS), as measured by the oxidation of 2′,7′-dichlorodihydrofluorescein. In addition, a significant decrease in the intracellular GSH level and the activities of major antioxidant enzymes were observed. We also observed lipid peroxidation-mediated oxidative DNA damage, reflected by an increase in 8-OH-dG level and loss of the ability of DNA to renature. When the cells were pretreated with the antioxidant N-acetylcysteine (NAC) or the spin trap α-phenyl-N-t-butylnitrone (PBN), lipid peroxidation-mediated cytotoxicity in U937 cells was protected. This effect seems to be due to the ability of NAC and PBN to reduce ROS generation induced by lipid peroxidation. These results suggest that lipid peroxidation resulted in a pro-oxidant condition of U937 cells by the depletion of GSH and inactivation of antioxidant enzymes, which consequently leads to a decrease in survival and oxidative damage to DNA. The results indicate that the peroxidation of lipid is probably one of the important intermediary events in oxidative stress-induced cellular damage. [Copyright &y& Elsevier]

The effects of chylomicron remnants on lipid accumulation in J774 macrophages, and the incorporation of radioactivity from remnant lipids radiolabelled with [[sup 3] H]oleate into cellular lipids was investigated. After 24 h of incubation with chylomicron remnants, there was considerable accumulation of lipid within the cells as assessed by staining with oil red O, indicating that the particles induce the formation of foam cells. Fatty acids released from the radiolabelled remnant lipids after uptake were found to be incorporated into cellular triacylglycerol (52%), phospholipid (37%) and cholesteryl ester (8%), but at higher remnant concentrations, the proportion used for triacylglycerol formation increased (up to 73%). When the macrophages were shifted into a pro-oxidising or pro-reducing state by incubation (24 h) with CuSO[sub 4] (2.5 μM) or N-acetylcysteine (5 mM), respectively, the incorporation of [[sup 3] H]oleate from remnant lipid into cellular triacylglycerol and phospholipid was increased by 20–30% in the more oxidised as compared with the more reduced cells. These findings indicate that exposure of J774 macrophages to chylomicron remnants leads to the accumulation of lipid within the cells, and that this process is enhanced by pro-oxidising conditions. We conclude, therefore, that both lipids of dietary origin and the redox balance within macrophages may have a significant role in the induction of foam cell formation.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

• Small molecule-based fluorescent probes for cellular antioxidants. • Physiological redox factors distinguish diseased cells from normal cells. • Characteristics of fluorogenic reactions mediated by antioxidants. • Summary of recent fluorescent probes for NAD(P)H, hNQO1, H 2 S, and others. • Introduction of in vitro and in vivo biological validation models for probes. Maintaining redox homeostasis is critical for cellular function. To maintain a redox balance, a cell defense system that regulates the production of endogenous oxidants and antioxidants is of vital importance. Many biomolecules act as oxidants or antioxidants in cells and demonstrate complex crosstalk systems. Effective monitoring and detection of a given biomolecule are essential for understanding complex redox signals and related pathological properties. In this review, we outline recent advances in the development of small molecule-based fluorescent probes capable of detecting several representative antioxidants such as reduced nicotinamide adenine dinucleotide (NADH), human NAD(P)H:quinone oxidoreductase 1 (hNQO1) and H 2 S, and exploring complex crosstalk with other redox reactive biomolecules, including H 2 O 2 , HClO, SO 2 and nitroreductase (NTR), by emitting fluorescence signals that are readily detected in vitro and in vivo. The basic design concepts involving small fluorescent molecules composed of a fluorescent reporter and recognition moiety that undergo a fluorogenic reaction in response to analytes are described. In addition, this review demonstrates the validation of such fluorescent molecules with a variety of biological models such as live cancer cells, cancer cell spheroids, tissues, mice, and zebrafish. Prospects for future directions are delineated by presenting the physiological importance of fluorescence-based detection of cellular antioxidants. [ABSTRACT FROM AUTHOR]