Molecular mechanisms of oxidative stress resistance induced by resveratrol: Specific and progressive induction of MnSOD

Robb, Ellen L.; Page, Melissa M.; Wiens, Brent; Stuart, Jeffrey A.

doi:10.1016/j.bbrc.2007.12.138

Cited by 128 publications

(89 citation statements)

References 29 publications

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“…Consistent with our data in human adipocytes, 50-150 mM RSV has been shown in vitro to reduce inflammation in murine 3T3-L1 adipocytes (21), to reduce oxidative stress in human lung epithelial cells (29,30), to reduce ER stress in mouse macrophages (31), to decrease TNFamediated NFkB activation in hepatocytes (32) and coronary arterial endothelial cells (33), and to enhance glucose transport in muscle (34). Thus, RSV reduces inflammation and enhances glucose and FA utilization in vivo and in vitro, although the mechanism is unknown.…”

Section: Discussionsupporting

confidence: 89%

Conjugated linoleic acid-mediated inflammation and insulin resistance in human adipocytes are attenuated by resveratrol

Kennedy

Overman

LaPoint

et al. 2009

Journal of Lipid Research

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Inflammation plays a role in trans-10, cis-12 (10,12)-conjugated linoleic acid (CLA)-mediated delipidation and insulin resistance in adipocytes. Given the anti-inflammatory role of resveratrol (RSV), we hypothesized that RSV would attenuate inflammation and insulin resistance caused by 10,12 CLA in human adipocytes. RSV blocked 10,12 CLA induction of the inflammatory response by preventing activation of extracellular signal-related kinase and induction of inflammatory gene expression (i.e., IL-6, IL-8, IL-1b) within 12 h. Similarly, RSV suppressed 10,12 CLA-mediated activation of the inflammatory prostaglandin pathway involving phospholipase A 2 , cyclooxygenase-2, and PGF 2a . In addition, RSV attenuated 10,12 CLA increase of intracellular calcium and reactive oxygen species associated with cellular stress, and activation of stress-related proteins (i.e., activating transcription factor 3, JNK) within 12 h. 10,12 CLA-mediated insulin resistance and suppression of fatty acid uptake and triglyceride content were attenuated by RSV. Finally, 10,12 CLA-mediated decrease of peroxisome proliferator-activated receptor g (PPARg) protein levels and activation of a peroxisome proliferator response element (PPRE) reporter were prevented by RSV. RSV increased the basal activity of PPRE, suggesting that RSV increases PPARg activity. Collectively, these data demonstrate for the first time that RSV prevents 10,12 CLAmediated insulin resistance and delipidation in human adipocytes by attenuating inflammation and cellular stress and increasing PPARg activity. Feeding a mixture of conjugated linoleic acid (CLA) isomers [i.e., trans-10, cis-12 (10,12) CLA and cis-9, trans-11 (9,11) CLA] reduces adiposity in animals (1) and some humans (2). The triglyceride (TG)-lowering properties of CLA appear to be due exclusively to the 10,12 isomer (3-5), and involve decreased uptake and metabolism of glucose and fatty acids (FA)s (6), and increased lipolysis (7) in adipocytes. These anti-obesity properties of 10,12 CLA are dependent on the activation of mitogen-activated protein kinase kinase/extracellular signal-related kinase (MEK/ERK) (6) and nuclear factor kB (NFkB) (8, 9) in adipocytes. These signaling pathways induced by 10,12 CLA are linked to the induction and secretion of cytokines (8, 9), which are known to antagonize peroxisome proliferator-activated receptor g (PPARg) target gene expression and insulin sensitivity (10-15). Consistent with these data, 10,12 CLA supplementation of humans is associated with hyperglycemia, insulin resistance, elevated levels of inflammatory prostaglandins (PGs) and cytokines, and dyslipidemia (16)(17)(18).Recently, supplementation of mice and 3T3-L1 adipocytes with 10,12 CLA has been shown to activate the integrated stress response (ISR) pathway (19), which is linked to inflammation, insulin resistance, and endoplasmic reticulum (ER) stress (20). Cellular stress can be caused by a relatively disproportional influx of macronutrients that adversely affect organelle function, including the mitoc...

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Section: Discussionsupporting

confidence: 89%

Conjugated linoleic acid-mediated inflammation and insulin resistance in human adipocytes are attenuated by resveratrol

Kennedy

Overman

LaPoint

et al. 2009

Journal of Lipid Research

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“…2A). The resveratrol effects on liver mitochondria in terms of H 2 O 2 generation can be explained by a direct action on complex I, or instead, as previously reported, by modulation of mitochondrial Manganesesuperoxide dismutase (Robb et al, 2008), increasing the flux of hydrogen peroxide production.…”

Section: Discussionsupporting

confidence: 58%

Resveratrol affects differently rat liver and brain mitochondrial bioenergetics and oxidative stress in vitro: Investigation of the role of gender

Moreira

Silva

Santos

et al. 2013

Food and Chemical Toxicology

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a b s t r a c tResveratrol (3,5,4 0 -trihydroxy-trans stilbene) is commonly recognized by its antioxidant properties. Despite its beneficial qualities, the toxic effects of this natural compound are still unknown. Since mitochondria are essential to support the energy-dependent regulation of several cell functions, the objective of this study was to evaluate resveratrol effects on rat brain and liver mitochondrial fractions from male and females regarding oxidative stress and bioenergetics. No basal differences were observed between mitochondrial fractions from males and females, except in liver mitochondria, the generation of H 2 O 2 by the respiratory chain is lower for female preparations. Resveratrol inhibited lipid peroxidation in preparations from both genders and organs. Furthermore, brain mitochondria in both gender groups appeared susceptible to resveratrol as seen by a decrease in state 3 respiration and alterations in mitochondrial membrane potential fluctuations during ADP phosphorylation. As opposed, liver mitochondria were less affected by resveratrol. Our data also demonstrates that resveratrol inhibits complex I activity in all mitochondrial preparations. The results suggest that brain mitochondria appear to be more susceptible to resveratrol effects, and gender appears to play a minor role. It remains to be determined if resveratrol effects on brain mitochondria contribute to deterioration of mitochondrial function or instead to mediate hormesis-mediated events.

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“…Atherosclerosis, diabetes mellitus, chronic obstructive pulmonary disease, and cancer are examples of diseases associated with ROS-induced chronic inflammation [43,45,46]. Laboratory models suggest these diseases can either be prevented, treated, or cured through attenuating ROS, which may be achieved through treatment with resveratrol [22,47,48]. To date, human trials in this area have been very limited.…”

Section: Oxidative Stress and Inflammationmentioning

confidence: 99%

Resveratrol and health – A comprehensive review of human clinical trials

Smoliga

Baur

Hausenblas

2011

Molecular Nutrition Food Res

502

308

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In the past decade, the small polyphenol resveratrol has received widespread attention as either a potential therapy or as a preventive agent for numerous diseases. Studies using purified enzymes, cultured cells, and laboratory animals have suggested that resveratrol has anti-aging, anti-carcinogenic, anti-inflammatory, and anti-oxidant properties that might be relevant to chronic diseases and/or longevity in humans. Although the supporting research in laboratory models is quite substantial, only recently data has emerged to describe the effects of resveratrol supplementation on physiological responses in humans. The limited number of human clinical trials that are available has largely described various aspects of resveratrol's safety and bioavailability, reaching a consensus that it is generally well-tolerated, but have poor bioavailability. Very few published human studies have explored the ability of resveratrol to achieve the physiological benefits that have been observed in laboratory models, although many clinical trials have recently been initiated. This review aims to examine the current state of knowledge on the effects of resveratrol on humans and to utilize this information to develop further guidelines for the implementation of human clinical trials.

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Molecular mechanisms of oxidative stress resistance induced by resveratrol: Specific and progressive induction of MnSOD

Cited by 128 publications

References 29 publications

Conjugated linoleic acid-mediated inflammation and insulin resistance in human adipocytes are attenuated by resveratrol

Conjugated linoleic acid-mediated inflammation and insulin resistance in human adipocytes are attenuated by resveratrol

Resveratrol affects differently rat liver and brain mitochondrial bioenergetics and oxidative stress in vitro: Investigation of the role of gender

Resveratrol and health – A comprehensive review of human clinical trials

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