Antimycin A and lipopolysaccharide cause the leakage of superoxide radicals from rat liver mitochondria

Piskernik, Christina; Haindl, Susanne; Behling, Tricia; Zanoni, Gerald; Kehrer, Ingeborg; Redl, Heinz; Kozlov, Andrey V.

doi:10.1016/j.bbadis.2008.01.007

Cited by 36 publications

(35 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, we tested the effect of ROCK1 on mtROS production in the glomeruli of control and STZ-induced diabetic mice. To specifically assess mitochondrial superoxide production, we performed Electron Paramagnetic Resonance (EPR) spectroscopy, and used 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine (CMH) as the spin trap (Piskernik et al, 2008; Pospisilik et al, 2007). We observed ~ 8-fold increase in the mtROS generation from the isolated kidney glomeruli of diabetic wild type mice, whereas this increase was prevented in diabetic ROCK1 −/− mice (Figure 4A, left panel ).…”

Section: Resultsmentioning

confidence: 99%

Mitochondrial Fission Triggered by Hyperglycemia Is Mediated by ROCK1 Activation in Podocytes and Endothelial Cells

et al. 2012

View full text Add to dashboard Cite

SUMMARY Several lines of evidence suggest that mitochondrial dysfunction plays a critical role in the pathogenesis of microvascular complications of diabetes, including diabetic nephropathy. However, the signaling pathways by which hyperglycemia leads to mitochondrial dysfunction are not fully understood. Here we examined the role of Rho-associated coiled-coil containing protein kinase 1 (ROCK1) on mitochondrial dynamics by generating two diabetic mouse models with targeted deletions of ROCK1, and an inducible podocyte-specific knock-in mouse expressing a constitutively active (cA) mutant of ROCK1. Our findings suggest that ROCK1 mediates hyperglycemia-induced mitochondrial fission by promoting dynamin-related protein-1 (Drp1) recruitment to the mitochondria. Deletion of ROCK1 in diabetic mice prevented mitochondrial fission, whereas podocyte-specific cA-ROCK1 mice exhibited increased mitochondrial fission. Importantly, we found that ROCK1 triggers mitochondrial fission by phosphorylating Drp1 at Serine 600 residue. These findings provide insights into the unexpected role of ROCK1 in a signaling cascade that regulates mitochondrial dynamics.

show abstract

Section: Resultsmentioning

confidence: 99%

Mitochondrial Fission Triggered by Hyperglycemia Is Mediated by ROCK1 Activation in Podocytes and Endothelial Cells

et al. 2012

View full text Add to dashboard Cite

show abstract

“…It revealed that O 2 À is generated only in mitochondria that have experienced a shock, but not in intact ones. 90 Considering that PUFAs are particularly oxygen-sensitive compounds, it is hypothesized that peroxidation of PUFAs is the initiating process of all biological oxidation reactions. Usually it was assumed so far that LPO reactions are initiated by superoxide and not by the reaction of lipid hydroperoxides produced by cell injury as outlined above.…”

Section: Spitellermentioning

confidence: 99%

Is Lipid Peroxidation of Polyunsaturated Acids the Only Source of Free Radicals That Induce Aging and Age-Related Diseases?

Spiteller

2010

Rejuvenation Research

View full text Add to dashboard Cite

The increase in free radicals is hypothesised to cause aging and age-related diseases. The most common source of free radicals is thought to be superoxide. This superoxide is claimed to be released from mitochondria during the enzymatic transformation of oxygen to water by a "leakage" process. This article presents evidence that leakage does not occur. Instead, protonated superoxide radicals are generated by lipid peroxidation processes. In nature, polyunsaturated fatty acids (PUFAs) represent particularly oxygen-sensitive compounds. Apparently, nature uses this sensitivity for signalling processes by producing lipidhydroperoxides (LOOHs) by any change to cell membrane structure. LOOHs easily undergo further enzymatic transformations to compounds which contribute to activation of genes. Bivalent metal ions within the active site of lipoxygenases catalyse LOOH production. The metal ions generate radicals which are transformed within the enzyme complex to non-radical molecules. Thus radicals never leave the enzyme complex except in severe stress situations. In this case the radical intermediates attack bonds, keeping the metal ion in its complex state. Thus, metal ions are released and react in a Fenton reaction with LOOH molecules produced earlier by lipoxygenase to form LO. radicals. Radicals are typically four orders of magnitude more reactive than non-radical molecules. Their action is not under genetic control, they attack nearly all biological molecules, destroying lipids, proteins, nucleic acids, hormones and enzymes until the radicals are quenched by scavenger molecules. The principal degradation routes are outlined in this review. Lysophospholipids are generated in large amounts after stress by activation of phospholipases and are transformed to LO. radicals. These can abstract a hydrogen radical from a lysophospholipid. The radical thus formed adds oxygen and decomposes to a 2-oxolysophospholipid and a HOO. radical (protonated superoxide). HOO. radicals in turn abstract hydrogen atoms from other molecules and produce H(2)O(2). Since any cell preparation method causes membrane destruction, it is inevitable that protonated superoxide is generated, explaining why H(2)O(2) molecules are found as "byproducts" of many reactions.

show abstract

“…Reactive oxygen and nitrogen species in tissues were determined by electron paramagnetic resonance (EPR) spectroscopy using the membrane-permeable spin probe 1-hydroxy-3-carboxy-2,2,5,5-tetramethyl-pyrrolidine hydrochloride (CPH). In an endotoxic shock model, we recently found increased RONS generation and oxidative or nitrosylative stress in the liver using CPH (1). Reactive oxygen and nitrogen species scavenging capacity was analyzed by investigating protein levels of superoxide dismutase 2 (SOD-2), an antioxidative defense enzyme, induced after conditions associated with increased oxidative stress, such as hepatic I/R (2) and endotoxic shock (3).…”

Section: Introductionmentioning

confidence: 99%

Reperfusion Does Not Induce Oxidative Stress but Sustained Endoplasmic Reticulum Stress in Livers of Rats Subjected to Traumatic-Hemorrhagic Shock

Duvigneau

Kozlov²,

Zifko³

et al. 2010

Shock

Self Cite

View full text Add to dashboard Cite

Oxidative stress is believed to accompany reperfusion and to mediate dysfunction of the liver after traumatic-hemorrhagic shock (THS). Recently, endoplasmic reticulum (ER) stress has been suggested as an additional factor. This study investigated whether reperfusion after THS leads to increased oxidative and/or ER stress in the liver. In a rat model, including laparotomy, bleeding until decompensation, followed by inadequate or adequate reperfusion phase, three time points were investigated: 40 min, 3 h, and 18 h after shock. The reactive oxygen and nitrogen species and its scavenging capacity (superoxide dismutase 2), the nitrotyrosine formation in proteins, and the lipid peroxidation together with the status of endogenous antioxidants (alpha-tocopherylquinone-alpha-tocopherol ratio) were investigated as markers for oxidative or nitrosylative stress. Mitochondrial function and cytochrome P450 isoform 1A1 activity were analyzed as representatives for hepatocyte function. Activation of the inositol-requiring enzyme 1/X-box binding protein pathway and up-regulation of the 78-kDa glucose-regulated protein were recorded as ER stress markers. Plasma levels of alanine aminotransferase and Bax/Bcl-XL messenger RNA (mRNA) ratio were used as indicators for hepatocyte damage and apoptosis induction. Oxidative or nitrosylative stress markers or representatives of hepatocyte function were unchanged during and short after reperfusion (40 min, 3 h after shock). In contrast, ER stress markers were elevated and paralleled those of hepatocyte damage. Incidence for sustained ER stress and subsequent apoptosis induction were found at 18 h after shock. Thus, THS or reperfusion induces early and persistent ER stress of the liver, independent of oxidative or nitrosylative stress. Although ER stress was not associated with depressed hepatocyte function, it may act as an early trigger of protracted cell death, thereby contributing to delayed organ failure after THS.

show abstract

Antimycin A and lipopolysaccharide cause the leakage of superoxide radicals from rat liver mitochondria

Cited by 36 publications

References 33 publications

Mitochondrial Fission Triggered by Hyperglycemia Is Mediated by ROCK1 Activation in Podocytes and Endothelial Cells

Mitochondrial Fission Triggered by Hyperglycemia Is Mediated by ROCK1 Activation in Podocytes and Endothelial Cells

Is Lipid Peroxidation of Polyunsaturated Acids the Only Source of Free Radicals That Induce Aging and Age-Related Diseases?

Reperfusion Does Not Induce Oxidative Stress but Sustained Endoplasmic Reticulum Stress in Livers of Rats Subjected to Traumatic-Hemorrhagic Shock

Contact Info

Product

Resources

About