Resveratrol reduces oxidative stress and cell death and increases mitochondrial antioxidants and XIAP in PC6.3-cells

Kairisalo, Minna; Bonomo, Alessandra; Hyrskyluoto, Alise; Mudò, Giuseppa; Belluardo, Natale; Korhonen, Laura; Lindholm, Dan

doi:10.1016/j.neulet.2010.11.042

Cited by 42 publications

(38 citation statements)

References 22 publications

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“…b Neuronal PC6.3 cells were treated with different concentrations of RSV and the activity of the PGC-1a promoter measured as above. Values are means ± SD, n = 3. p \ 0.001 for RSV versus C for all concentrations PGC-1a is neuroprotective in dopaminergic neurons 1163 stress [36]. In line with this, we show here that 5-10 lM RSV elevates SOD2 and Trx2 in cultured dopaminergic cells.…”

Section: Discussionsupporting

confidence: 84%

“…In line with this, we show here that 5-10 lM RSV elevates SOD2 and Trx2 in cultured dopaminergic cells. SOD2 and Trx2 regulate oxidative stress at the level of the mitochondria and these proteins are regulated in brain neurons partly by NF-jB activation that is induced by various signals including XIAP [28,36]. In this study, we observed no change in NF-jB signaling by RSV, suggesting another mechanism of action.…”

Section: Discussionmentioning

confidence: 43%

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Transgenic expression and activation of PGC-1α protect dopaminergic neurons in the MPTP mouse model of Parkinson’s disease

Mudò

Mäkelä

Liberto

et al. 2011

Cell. Mol. Life Sci.

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272

239

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Mitochondrial dysfunction and oxidative stress occur in Parkinson's disease (PD), but little is known about the molecular mechanisms controlling these events. Peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) is a transcriptional coactivator that is a master regulator of oxidative stress and mitochondrial metabolism. We show here that transgenic mice overexpressing PGC-1α in dopaminergic neurons are resistant against cell degeneration induced by the neurotoxin MPTP. The increase in neuronal viability was accompanied by elevated levels of mitochondrial antioxidants SOD2 and Trx2 in the substantia nigra of transgenic mice. PGC-1α overexpression also protected against MPTP-induced striatal loss of dopamine, and mitochondria from PGC-1α transgenic mice showed an increased respiratory control ratio compared with wild-type animals. To modulate PGC-1α, we employed the small molecular compound, resveratrol (RSV) that protected dopaminergic neurons against the MPTP-induced cell degeneration almost to the same extent as after PGC-1α overexpression. As studied in vitro, RSV activated PGC-1α in dopaminergic SN4741 cells via the deacetylase SIRT1, and enhanced PGC-1α gene transcription with increases in SOD2 and Trx2. Taken together, the results reveal an important function of PGC-1α in dopaminergic neurons to combat oxidative stress and increase neuronal viability. RSV and other compounds acting via SIRT1/PGC-1α may prove useful as neuroprotective agents in PD and possibly in other neurological disorders.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 43%

Transgenic expression and activation of PGC-1α protect dopaminergic neurons in the MPTP mouse model of Parkinson’s disease

Mudò

Mäkelä

Liberto

et al. 2011

Cell. Mol. Life Sci.

Self Cite

272

239

View full text Add to dashboard Cite

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“…[22][23][24] SIRT1 has been shown to deacetylate both histones and a wide range of non-histone proteins; thus it is involved in a wide range of functions including endothelial homeostasis, 25,26 apoptosis, 27,28 cell-cycle regulation, transcriptional silencing and oxidative stress. [29][30][31] Several pieces of evidence suggest that SIRT1 acts as a longevity factor in vascular tissue; in particular, its critical role in endothelial homeostasis by Figure 4 The protein level of SIRT1, FOXO3a, P53 in penile tissues. SIRT1 protein decreased in diabetic group and increased in resveratrol-treated group.…”

Section: Resveratrol Restored Icp and Increased The Ratio Of Icp/mapmentioning

confidence: 99%

Resveratrol, an activator of SIRT1, restores erectile function in streptozotocin-induced diabetic rats

Yao¹,

Wan²,

Qiu³

et al. 2013

Asian J Androl

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The high incidence of erectile dysfunction (ED) in diabetes highlights a need for effective treatment strategies. Resveratrol, an activator of silent information regulator 2-related enzymes 1 (sirtuin1, SIRT1), has received attention for its valuable effects in cancer, neurodegenerative diseases, longevity and cardiovascular disease. To explore the effects of resveratrol in diabetes-induced ED, resveratrol was administered to rats with streptozocin (65 mg kg 21 )-induced diabetes. Erectile function, cavernous structure, tissue protein expression of silent information regulator 2-related enzymes 1 (sirtuin1, SIRT1), p53 and forkhead transcription factor O 3a (FOXO3a), superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels in the corpora cavernosa were studied. We found that SIRT1 was expressed in cavernosal tissue, and it was downregulated in the corpora of diabetic rats. The administration of resveratrol upregulated the expression of SIRT1 and restored erectile function. In contrast, resveratrol downregulated the expression of p53 and FOXO3a, which regulate apoptosis and oxidative stress. Furthermore, the resveratrol-treated group showed an improvement in smooth muscle content, SOD activity and MDA levels when compared with the diabetic group. Therefore, the ability of resveratrol to improve diabetes-induced ED is likely related to its activation of SIRT1 expression, thus causing the suppression of apoptosis and resistance towards oxidative stress.

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“…by activating the nuclear factor erythroid-derived 2-related factor 2 (Nrf2) transcription factor pathway. 120,121 Resveratrol as well as quercetin, catechins, and procyanidins have been demonstrated to counteract oxidative stress-induced apoptosis by increasing the level of mitochondrial antioxidant enzymes and modulating specific signalling pathways and kinase activities, [122][123][124][125][126][127][128][129][130][131] which result in a complex regulation of the balance between pro-and anti-apoptotic Bcl-2 family members. [132][133][134][135][136] These activities might be due to the capability of polyphenols to accumulate in mitochondria.…”

Section: Polyphenols As Cytoprotective Compounds Via Their Antioxidanmentioning

confidence: 99%

Role of polyphenols in cell death control

Giovannini¹,

Masella²

2012

Nutritional Neuroscience

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Dietary consumption of fruit, vegetables, fish, and olive oil has been demonstrated to exert beneficial effects on human health. This finding may be due to the high content of antioxidant compounds including polyphenols. Current evidence strongly supports a contribution of polyphenols to the prevention of several chronic degenerative diseases such as cancer, atherosclerosis and cardiovascular diseases, central nervous system disorders, as well as aging. Apoptosis is a genetically controlled and evolutionarily conserved form of cell death of critical importance for the maintenance of tissue homeostasis in the adult organism. The malfunction of the death machinery may play a primary role in various pathologic processes, leading to proliferative or degenerative diseases. Polyphenols can interact with specific steps and/or proteins regulating the apoptotic process in different ways depending on their concentration, the cell system, the type or stage of the pathological process. Because of their ability to modulate cell death, polyphenols have been proposed as chemopreventive and therapeutic agents. This paper reviews and discusses the last 3-year findings related to the principal molecular mechanisms involved in the control of the balance between apoptosis and cell proliferation exerted by polyphenols.

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Resveratrol reduces oxidative stress and cell death and increases mitochondrial antioxidants and XIAP in PC6.3-cells

Cited by 42 publications

References 22 publications

Transgenic expression and activation of PGC-1α protect dopaminergic neurons in the MPTP mouse model of Parkinson’s disease

Transgenic expression and activation of PGC-1α protect dopaminergic neurons in the MPTP mouse model of Parkinson’s disease

Resveratrol, an activator of SIRT1, restores erectile function in streptozotocin-induced diabetic rats

Role of polyphenols in cell death control

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