SIRT1 regulates oxidant- and cigarette smoke-induced eNOS acetylation in endothelial cells: Role of resveratrol

Arunachalam, Gnanapragasam; Yao, Hongwei; Sundar, Isaac K.; Caito, Samuel; Rahman, Irfan

doi:10.1016/j.bbrc.2010.01.080

Cited by 170 publications

(137 citation statements)

References 32 publications

Supporting

Mentioning

127

Contrasting

Unclassified

Order By: Relevance

“…Chronic CS exposure reduced the level of SIRT1 in BAL cells (mainly composed of macrophages) and lung epithelial cells in mice. This is consistent with our previous studies showing SIRT1 reduction in monocytes/macrophages, lung epithelial cells, endothelial cells, and fibroblasts treated with CS extract in vitro (18,38,68,69). Interestingly, SA-β-gal activity in lungs was increased in mice with SIRT1 deficiency in Clara cells, but not in myeloid cells, compared with corresponding WT littermates in response to elastase administration.…”

Section: Discussionsupporting

confidence: 92%

SIRT1 protects against emphysema via FOXO3-mediated reduction of premature senescence in mice

Yao

Chung²,

Hwang³

et al. 2012

J. Clin. Invest.

Self Cite

307

343

View full text Add to dashboard Cite

Chronic obstructive pulmonary disease/emphysema (COPD/emphysema) is characterized by chronic inflammation and premature lung aging. Anti-aging sirtuin 1 (SIRT1), a NAD + -dependent protein/histone deacetylase, is reduced in lungs of patients with COPD. However, the molecular signals underlying the premature aging in lungs, and whether SIRT1 protects against cellular senescence and various pathophysiological alterations in emphysema, remain unknown. Here, we showed increased cellular senescence in lungs of COPD patients. SIRT1 activation by both genetic overexpression and a selective pharmacological activator, SRT1720, attenuated stress-induced premature cellular senescence and protected against emphysema induced by cigarette smoke and elastase in mice. Ablation of Sirt1 in airway epithelium, but not in myeloid cells, aggravated airspace enlargement, impaired lung function, and reduced exercise tolerance. These effects were due to the ability of SIRT1 to deacetylate the FOXO3 transcription factor, since Foxo3 deficiency diminished the protective effect of SRT1720 on cellular senescence and emphysematous changes. Inhibition of lung inflammation by an NF-κB/IKK2 inhibitor did not have any beneficial effect on emphysema. Thus, SIRT1 protects against emphysema through FOXO3-mediated reduction of cellular senescence, independently of inflammation. Activation of SIRT1 may be an attractive therapeutic strategy in COPD/emphysema.

show abstract

Section: Discussionsupporting

confidence: 92%

SIRT1 protects against emphysema via FOXO3-mediated reduction of premature senescence in mice

Yao

Chung²,

Hwang³

et al. 2012

J. Clin. Invest.

Self Cite

307

343

View full text Add to dashboard Cite

show abstract

“…Endothelial dysfunction plays an important role in pathogenesis of emphysema, and CSinduced emphysematous alveolar destruction, which is almost avascular, associated with decreased expression of endothelial nitric oxide synthase (35, 38). SIRT1 deacetylates lysines at position K496 and K506 in the calmodulin-binding domain of endothelial nitric oxide synthase, leading to enhanced nitric oxide production, which is vital for endothelial-dependent vasorelaxation, cell survival, migration, and postnatal neovascularization (10,84). NO activates the SIRT1 promoter, thereby increasing SIRT1 mRNA and protein levels (100,105), suggesting that a positive feedback mechanism exists between SIRT1 and endothelial nitric oxide synthase (110).…”

Section: Fig 6 Role Of Sirt1 Foxo3mentioning

confidence: 99%

Oxidative Stress and Chromatin Remodeling in Chronic Obstructive Pulmonary Disease and Smoking-Related Diseases

Sundar

Yao

Rahman

2013

Antioxidants & Redox Signaling

Self Cite

157

104

View full text Add to dashboard Cite

Significance: Chronic obstructive pulmonary disease (COPD) is predominantly a tobacco smoke-triggered disease with features of chronic low-grade systemic inflammation and aging (inflammaging) of the lung associated with steroid resistance induced by cigarette smoke (CS)-mediated oxidative stress. Oxidative stress induces various kinase signaling pathways leading to chromatin modifications (histone acetylation/deacetylation and histone methylation/demethylation) in inflammation, senescence, and steroid resistance. Recent Advances: Histone mono-, di-, or tri-methylation at lysine residues result in either gene activation (H3K4, H3K36, and H3K79) or repression (H3K9, H3K27, and H3K20). Cross-talk occurs between various epigenetic marks on histones and DNA methylation. Both CS and oxidants alter histone acetylation/deacetylation and methylation/ demethylation leading to enhanced proinflammatory gene expression. Chromatin modifications occur in lungs of patients with COPD. Histone deacetylase 2 (HDAC2) reduction (levels and activity) is associated with steroid resistance in response to oxidative stress. Critical Issues: Histone modifications are associated with DNA damage/repair and epigenomic instability as well as premature lung aging, which have implications in the pathogenesis of COPD. HDAC2/SIRTUIN1 (SIRT1)-dependent chromatin modifications are associated with DNA damage-induced inflammation and senescence in response to CS-mediated oxidative stress. Future Directions: Understanding CS/oxidative stress-mediated chromatin modifications and the cross-talk between histone acetylation and methylation will demonstrate the involvement of epigenetic regulation of chromatin remodeling in inflammaging. This will lead to identification of novel epigenetic-based therapies against COPD and other smoking-related lung diseases. Pharmacological activation of HDAC2/SIRT1 or reversal of their oxidative post-translational modifications may offer therapies for treatment of COPD and CS-related diseases based on epigenetic histone modifications.

show abstract

“…47,48 The oxidative stress-related changes might be associated with sirtuins, because they can be modulated by oxidative challenges. [49][50][51] Aerobic exercise, which is often used to study the effects of physical activity on brain function, decreases the level of circulating IGF-1 with exercise of moderate intensity and long duration 52 ; however, the findings of Trejo and co-workers 53 on exercising in wild-type and mutant mice with low levels of serum IGF-1 show the complexity of IGF-1 in exercise physiology.…”

Section: Introductionmentioning

confidence: 99%

Combined Exercise and Insulin-Like Growth Factor-1 Supplementation Induces Neurogenesis in Old Rats, but Do Not Attenuate Age-Associated DNA Damage

Koltai

Zhao

Lacza

et al. 2011

Rejuvenation Research

View full text Add to dashboard Cite

We have investigated the effects of 2 weeks of insulin-like growth factor-1 (IGF-1) supplementation (5 mg/kg per day) and 6 weeks of exercise training (60% of the maximal oxygen consumption [VO 2 max]) on neurogenesis, DNA damage/repair, and sirtuin content in the hippocampus of young (3 months old) and old (26 months old) rats. Exercise improved the spatial memory of the old group, but IGF-1 supplementation eliminated this effect. An age-associated decrease in neurogenesis was attenuated by exercise and IGF-1 treatment. Aging increased the levels of 8-oxo-7,8-dihydroguanine (8-oxoG) and the protein Ku70, indicating the role of DNA damage in age-related neuropathology. Acetylation of 8-oxoguanine DNA glycosylase (OGG1) was detected in vivo, and this decreased with aging. However, in young animals, exercise and IGF-1 treatment increased acetylated (ac) OGG1 levels. Sirtuin 1 (SIRT1) and SIRT3, as DNA damage-associated lysine deacetylases, were measured, and SIRT1 decreased with aging, resulting in a large increase in acetylated lysine residues in the hippocampus. On the other hand, SIRT3 increased with aging. Exercise-induced neurogenesis might not be a causative factor of increased spatial memory, because IGF-1 plus exercise can induce neurogenesis in the hippocampus of older rats. Data revealed that the age-associated increase in 8-oxoG levels is due to decreased acetylation of OGG1. Age-associated decreases in SIRT1 and the associated increase in lysine acetylation, in the hippocampus, could have significant impact on function and thus, could suggest a therapeutic target.

show abstract

SIRT1 regulates oxidant- and cigarette smoke-induced eNOS acetylation in endothelial cells: Role of resveratrol

Cited by 170 publications

References 32 publications

SIRT1 protects against emphysema via FOXO3-mediated reduction of premature senescence in mice

SIRT1 protects against emphysema via FOXO3-mediated reduction of premature senescence in mice

Oxidative Stress and Chromatin Remodeling in Chronic Obstructive Pulmonary Disease and Smoking-Related Diseases

Combined Exercise and Insulin-Like Growth Factor-1 Supplementation Induces Neurogenesis in Old Rats, but Do Not Attenuate Age-Associated DNA Damage

Contact Info

Product

Resources

About