Global Gene Expression Profiling Reveals Functional Importance of Sirt2 in Endothelial Cells under Oxidative Stress

Liu, Junni; Wu, Xiao; Wang, Xi; Zhang, Yun; Bu, Peili; Zhang, Qunye; Jiang, Fan

doi:10.3390/ijms14035633

Cited by 35 publications

(19 citation statements)

References 40 publications

(53 reference statements)

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“…SIRT2 deacetylates receptor-interacting protein (RIP)-1, facilitating cellular necrosis 55 . Consistent with this, in culture, pharmocological inhibition of SIRT2 prevents endothelial cells from H 2 O 2 -induced cell death 56 , suggesting that SIRT2 aggravates cardiovascular diseases. Although SIRT2 was reported to increase longevity in mice 57 , further study is required to determine roles of SIRT2 in vascular aging.…”

Section: Roles Of Sirt Proteins In Vascular Agingsupporting

confidence: 72%

Sirtuins, Cell Senescence, and Vascular Aging

Kida

Goligorsky

2016

Canadian Journal of Cardiology

215

161

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The sirtuin (SIRTs) constitute a class of proteins with NAD+-dependent deacetylase or ADP-ribosyltransferase activity. Seven SIRT family members have been identified in mammals, from SIRT1, the best studied for its role in vascular aging, to SIRT7. SIRT1 and SIRT2 are localized both in the nucleus and cytoplasm. SIRT3, SIRT4, and SIRT5 are mitochondrial, while SIRT6 and SIRT7 are nuclear. Extensive studies have clearly revealed that SIRT proteins regulate diverse cell functions and responses to stressors. Vascular aging involves the aging process (senescence) of endothelial and vascular smooth muscle cells. Two types of cell senescence have been identified: (1) replicative senescence with telomere attrition and (2) stress-induced premature senescence without telomere involvement. Both types of senescence induce vascular cell growth arrest and loss of vascular homeostasis, contributing to the initiation and progression of cardiovascular diseases. Previous mechanistic studies have revealed in detail that SIRT1, SIRT3, and SIRT6 demonstrate protective functions against vascular aging, while definite vascular function of other SIRTs is under investigation. Thus, direct SIRT modulation and NAD+ stimulation of SIRT are promising candidates for cardiovascular disease therapy. A small number of pilot studies have been conducted to assess SIRT modulation in humans. These clinical studies have not yet provided convincing evidence that SIRT proteins alleviate morbidity and mortality in patients with cardiovascular diseases. The outcomes of multiple ongoing clinical trials are awaited to define the efficacy of SIRT modulators and SIRT activators in cardiovascular diseases, along with the potential adverse effects of chronic SIRT modulation.

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Section: Roles Of Sirt Proteins In Vascular Agingsupporting

confidence: 72%

Sirtuins, Cell Senescence, and Vascular Aging

Kida

Goligorsky

2016

Canadian Journal of Cardiology

215

161

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“…We also show an up‐regulation of HSP27 and P‐HSP27. Wild‐type HSP27 lowers the levels of ROS by raising intracellular glutathione (36), whereas P‐HSP27 prevents apoptosis interfering with the caspase cascade (33). In addition, HSP27 maintains the stability of actin fibers (37), a function that might be relevant under gravitational unloading to preserve the remaining components of the cytoskeleton.…”

Section: Resultsmentioning

confidence: 99%

The dynamic adaptation of primary human endothelial cells to simulated microgravity

Cazzaniga¹,

Locatelli²,

Castiglioni³

et al. 2019

The FASEB Journal

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Culture of human endothelial cells for 10 d in real microgravity onboard the International Space Station modulated more than 1000 genes, some of which are involved in stress response. On Earth, 24 h after exposure to simulated microgravity, endothelial cells up‐regulate heat shock protein (HSP) 70. To capture a broad view of endothelial stress response to gravitational unloading, we cultured primary human endothelial cells for 4 and 10 d in the rotating wall vessel, a U.S. National Aeronautics and Space Administration–developed surrogate system for benchtop microgravity research on Earth. We highlight the crucial role of the early increase of HSP70 because its silencing markedly impairs cell survival. Once HSP70 up‐regulation fades away after 4 d of simulated microgravity, a complex and articulated increase of various stress proteins (sirtuin 2, paraoxonase 2, superoxide dismutase 2, p21, HSP27, and phosphorylated HSP27, all endowed with cytoprotective properties) occurs and counterbalances the up‐regulation of the pro‐oxidant thioredoxin interacting protein (TXNIP). Interestingly, TXNIP was the most overexpressed transcript in endothelial cells after spaceflight. We conclude that HSP70 up‐regulation sustains the initial adaptive response of endothelial cells to mechanical unloading and drives them toward the acquisition of a novel phenotype that maintains cell viability and function through the sequential involvement of different stress proteins.—Cazzaniga, A., Locatelli, L., Castiglioni, S., Maier, J. A. M. The dynamic adaptation of primary human endothelial cells to simulated microgravity. FASEB J. 33, 5957–5966 (2019). http://www.fasebj.

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“…Cardus et al showed that SIRT6 depletion by RNA interference in HUVECs and aortic endothelial cells reduced cell proliferation, increased the fraction of senescence‐associated β‐galactosidase‐positive cells, and diminished the ability of the cells to form tubule networks on Matrigel. Finally, Liu et al found that the pharmacologic inhibition of SIRT2 attenuates oxidant‐induced cell toxicity in endothelial cells. Collectively, these data emphasize the important protective role of sirtuins, especially SIRT1, in endothelial cells; preliminary data are emerging about a functionally important role of other sirtuins in endothelial protection.…”

Section: Aging In the Vascular Systemmentioning

confidence: 99%