Oxidative stress basically defines a condition in which prooxidant-antioxidant balance in the cell is disturbed; cellular biomolecules undergo severe oxidative damage, ultimately compromising cells viability. In recent years, a number of studies have shown that oxidative stress could cause cellular apoptosis via both the mitochondria-dependent and mitochondria-independent pathways. Since these pathways are directly related to the survival or death of various cell types in normal as well as pathophysiological situations, a clear picture of these pathways for various active molecules in their biological functions would help designing novel therapeutic strategy. This review highlights the basic mechanisms of ROS production and their sites of formation; detail mechanism of both mitochondria-dependent and mitochondria-independent pathways of apoptosis as well as their regulation by ROS. Emphasis has been given on the redox-sensitive ASK1 signalosome and its downstream JNK pathway. This review also describes the involvement of oxidative stress under various environmental toxin- and drug-induced organ pathophysiology and diabetes-mediated apoptosis. We believe that this review would provide useful information about the most recent progress in understanding the mechanism of oxidative stress-mediated regulation of apoptotic pathways. It will also help to figure out the complex cross-talks between these pathways and their modulations by oxidative stress. The literature will also shed a light on the blind alleys of this field to be explored. Finally, readers would know about the ROS-regulated and apoptosis-mediated organ pathophysiology which might help to find their probable remedies in future.

Oxidative stress: the mitochondria-dependent and mitochondria-independent pathways of apoptosis

Improvements in health care and lifestyle have led to an elevated lifespan and increased focus on age-associated diseases, such as neurodegeneration, cardiovascular disease, frailty and arteriosclerosis. In all these chronic diseases protein, lipid or nucleic acid modifications are involved, including cross-linked and non-degradable aggregates, such as advanced glycation end products (AGEs). Formation of endogenous or uptake of dietary AGEs can lead to further protein modifications and activation of several inflammatory signaling pathways. This review will give an overview of the most prominent AGE-mediated signaling cascades, AGE receptor interactions, prevention of AGE formation and the impact of AGEs during pathophysiological processes.

Role of advanced glycation end products in cellular signaling

Type 2 diabetes mellitus (T2DM) is a very complex and multifactorial metabolic disease characterized by insulin resistance and β cell failure leading to elevated blood glucose levels Hyperglycemia is suggested to be the main cause of diabetic complications, which not only decrease life quality and expectancy, but are also becoming a problem regarding the financial burden for health care systems Therefore, and to counteract the continually increasing prevalence of diabetes, understanding the pathogenesis, the main risk factors, and the underlying molecular mechanisms may establish a basis for prevention and therapy In this regard, research was performed revealing further evidence that oxidative stress has an important role in hyperglycemia-induced tissue injury as well as in early events relevant for the development of T2DM The formation of advanced glycation end products (AGEs), a group of modified proteins and/or lipids with damaging potential, is one contributing factor On the one hand it has been reported that AGEs increase reactive oxygen species formation and impair antioxidant systems, on the other hand the formation of some AGEs is induced per se under oxidative conditions Thus, AGEs contribute at least partly to chronic stress conditions in diabetes As AGEs are not only formed endogenously, but also derive from exogenous sources, ie, food, they have been assumed as risk factors for T2DM However, the role of AGEs in the pathogenesis of T2DM and diabetic complications—if they are causal or simply an effect—is only partly understood This review will highlight the involvement of AGEs in the development and progression of T2DM and their role in diabetic complications

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Advanced Glycation End Products and Oxidative Stress in Type 2 Diabetes Mellitus

Nox Enzymes, ROS, and Chronic Disease: An Example of Antagonistic Pleiotropy

Increased oxidative stress plays an important role in the pathophysiology of cardiovascular diseases such as hypertension, atherosclerosis, diabetes, cardiac hypertrophy, heart failure, and ischemia–reperfusion. Although several sources of reactive oxygen species (ROS) may be involved, a family of NADPH oxidases appears to be especially important for redox signaling and may be amenable to specific therapeutic targeting. These include the prototypic Nox2 isoform-based NADPH oxidase, which was first characterized in neutrophils, as well as other NADPH oxidases such as Nox1 and Nox4. These Nox isoforms are expressed in a cell- and tissue-specific fashion, are subject to independent activation and regulation, and may subserve distinct functions. This article reviews the potential roles of NADPH oxidases in both cardiovascular physiological processes (such as the regulation of vascular tone and oxygen sensing) and pathophysiological processes such as endothelial dysfunction, inflammation, hypertrophy, apoptosi...

/pdf/nadph-oxidases-in-cardiovascular-health-and-disease-2o8ehc9qa2.pdf

NADPH oxidases in cardiovascular health and disease.

Background— Nonenzymatic glycation that results in the production of early-glycation Amadori-modified proteins and advanced-glycation end products may be important in the pathogenesis of diabetic complications. However, the effects of early-glycated proteins, such as glycated serum albumin (Gly-BSA), are poorly defined. In this study, we investigated the effects of Gly-BSA on reactive oxygen species (ROS) production by cardiomyocytes. Methods and Results— Cultured neonatal rat cardiomyocytes were incubated with Gly-BSA or vehicle (bovine serum albumin [BSA]) for up to 48 hours. Gly-BSA dose-dependently increased in situ ROS production (whole-cell dichlorodihydrofluorescein fluorescence), with an optimum effect at 400 μg/mL after 24-hour incubation (152±10% versus BSA 100%; P<0.01). Treatment with the NADPH oxidase inhibitor apocynin, a Nox2 (gp91phox) antisense oligonucleotide (Nox2 AS), or the peptide gp91ds-tat significantly reduced Gly-BSA–induced ROS production at 24 hours (68.5±2.2%, 61.4±8.3%, and 5...

Ay Lin Kho

Papers

Glycated Proteins Stimulate Reactive Oxygen Species Production in Cardiac Myocytes Involvement of Nox2 (gp91phox)-Containing NADPH Oxidase