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Mitochondrial Stress and ROS

BioFiles 2011, 6.4, 22.

Oxidative stress is implicated in the pathogenesis of lipotoxicity in both animal and human studies. Chronic oxidative stress is linked to insulin resistance in multiple tissues. Oxidative stress is mediated, in part, by reactive oxygen species produced by multiple cellular processes and controlled by cellular antioxidant mechanisms such as enzymatic scavengers or antioxidant modulators. When ROS production exceeds the cellular antioxidant capacity, oxidative damage to cellular components such as proteins, lipids, and DNA occurs. Multiple pathways can contribute to cellular ROS formation, including the mitochondrial electron transport chain (ETC), inflammatory signaling, and endoplasmic reticulum stress.

The ETC is the major source of endogenous superoxide production in the cell. As electrons pass through the ETC, a small fraction escape and prematurely react with molecular oxygen resulting in the production of superoxide. An excess of nutrients will theoretically increase electron flux through the ETC with a resulting increase in the production of superoxide. Excessive ROS production may induce insulin resistance by the activation of stress-activated signaling cascades or by causing damage to mitochondrial proteins and DNA.

Enzymatic Scavengers

Multiple enzymatic scavengers are utilized by the cell to limit damage from reactive oxygen species. These scavengers include members of the superoxide dismutase (SOD) family, catalase, and glutathione peroxidase.


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Enzymes Involved in Oxidative Stress

 

Name Description Catalog No.
Catalase from bovine liver Catalase activates the decomposition of hydrogen peroxide, a reactive oxygen species, into water and oxygen. It functions as a natural antioxidant, protecting cells against oxidative damage to proteins, lipids and nucleic acids. Catalase has also been used to study the role reactive oxygen species play in gene expression and apoptosis. C9322
Catalase from human erythrocytes Catalase activates the decomposition of hydrogen peroxide, a reactive oxygen species, into water and oxygen. It functions as a natural antioxidant, protecting cells against oxidative damage to proteins, lipids and nucleic acids. Catalase has also been used to study the role reactive oxygen species play in gene expression and apoptosis. C3556
Glutathione Peroxidase from bovine erythrocytes G6137
Glutathione Peroxidase from human erythrocytes G4013
Nitric Oxide Synthase, Inducible from mouse NOS is responsible for the biosynthesis of nitric oxide from L-arginine. iNOS is not calcium/calmodulin dependent and has a Km = 16 µM for L-arginine. N2783
Peroxiredoxin I Active human Human Peroxiredoxin I (GenBank Accession No. NM_005614), full length, with N-terminal HIS6 tag, MW = 23 kDa, expressed in a Baculovirus infected Sf9 cell expression system. SRP0202
Peroxiredoxin II Active human Human Peroxiredoxin 2, full length (Genbank accession number NM_005809) with N-terminal HIS tag, MW = 22.7 kDa, expressed in Baculovirus infected Sf9 cell expression system. SRP0203
Protein Disulfide Isomerase from bovine liver Facilitates formation of the correct disulfide bonds by promoting rapid reshuffling of disulfide pairings. P3818
Superoxide Dismutase bovine   S9697
Superoxide Dismutase from bovine erythrocytes Catalyzes the dismutation of superoxide radicals to hydrogen peroxide and molecular oxygen. Plays a critical role in the defense of cells against the toxic effects of oxygen radicals. Competes with nitric oxide (NO) for superoxide anion (which reacts with NO to form peroxynitrite), thereby SOD promotes the activity of NO. SOD has also been shown to suppress apoptosis in cultured rat ovarian follicles, neural cell lines, and transgenic mice. S7571
Superoxide Dismutase from human erythrocytes Catalyzes the dismutation of superoxide radicals to hydrogen peroxide and molecular oxygen. Plays a critical role in the defense of cells against the toxic effects of oxygen radicals. Competes with nitric oxide (NO) for superoxide anion (which reacts with NO to form peroxynitrite), thereby SOD promotes the activity of NO. SOD has also been shown to suppress apoptosis in cultured rat ovarian follicles, neural cell lines, and transgenic mice. S9636
Thioredoxin Reductase from rat liver Thioredoxin reductase (TrxR) is a NADPH-dependent oxidoreductase containing one FAD per subunit that reduces the active site disulfide in oxidized thioredoxin (Trx). T9698

 

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Products for Studying Oxidative Stress

 

Name Description Catalog No.
Ceramide from bovine brain 22244
Dexamethasone An anti-inflammatory glucocorticoid with a range of effects on cell survival, cell signaling and gene expression. Use to study apoptosis, cell signaling pathways and gene expression. Glucocorticoid antiinflammatory agent. D4902
2',7'-Dichlorofluorescin diacetate Cell-permeable probe is de-esterified intracellularly and turns to highly fluorescent 2',7'-dichlorofluorescin upon oxidation. D6883
Dihydroethidium Redox indicator. Blue fluorescence until oxidized to ethidium. D7008
Dihydrorhodamine 123 D1054
2,4-Dinitrophenol D198501
Flavin adenine dinucleotide disodium salt hydrate F6625
ß-Nicotinamide adenine dinucleotide, reduced disodium salt hydrate N8129
ß-Nicotinamide adenine dinucleotide, reduced disodium salt hydrate N1161
Sodium azide 71289

 

Free Radicals

Free radicals, such as reactive oxygen species, cause cellular damage via cellular "rusting".

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Antioxidants

 

Name Description Catalog No.
N-Acetyl-l-cysteine Antioxidant and mucolytic agent. Increases cellular pools of free radical scavengers. Reported to prevent apoptosis in neuronal cells but induce apoptosis in smooth muscle cells. Inhibits HIV replication. May serve as a substrate for microsomal glutathione transferase. A9165
Aminoguanidine hemisulfate salt Inhibits both constitutive and inducible nitric oxide synthetase. A7009
 
L-Glutathione reduced Endogenous antioxidant that plays a major role in reducing reactive oxygen species formed during cellular metabolism and the respiratory burst. Glutathione- S-transferase catalyzes the formation of glutathione thioethers with xenobiotics, leukotrienes, and other molecules that have an electrophilic center. Glutathione also forms disulfide bonds with cysteine residues in proteins. Via these mechanisms, it can have the paradoxical effect of reducing the efficacy of anti-cancer agents. G4251
(±)-α-Lipoic acid Antioxidant and coenzyme needed for the activity of enzyme complexes such as pyruvate dehydrogenase and glycine decarboxylase. T1395
Lipoic acid, reduced T8260
Nicotinamide N0636

 

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Materials

     
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