Angiotensin II induces microtubule reorganization mediated by a deacetylase SIRT2 in endothelial cells

Hashimoto-Komatsu, Aiko; Hirase, Tetsuaki; Asaka, Machiko; Node, Koichi

doi:10.1038/hr.2011.64

Cited by 42 publications

(37 citation statements)

References 22 publications

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“…A previous study has shown that Sirt2 may be implicated in mediating angiotensin II-induced endothelial cell migration via modulating α-tubulin acetylation and microtubule reorganization [40]. Consistent with this observation, we identified (and confirmed with qPCR) that Sirt2 knock down altered the expression of several genes involved in cytoskeletal organization, cell contraction and migration, such as CALD1 (caldesmon) and CNN2 (calponin) [41,42].…”

Section: Resultssupporting

confidence: 88%

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

Liu

Wang

et al. 2013

IJMS

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The NAD+-dependent deacetylases Sirt1 and Sirt2 mediate cellular stress responses and are highly expressed in vascular endothelial cells. In contrast to the well-documented protective actions of Sirt1, the role of endothelial Sirt2 remains unknown. Using cDNA microarray and PCR validation, we examined global gene expression changes in response to Sirt2 knock down in primary human umbilical vein endothelial cells under oxidative stress. We found that Sirt2 knock down changed expression of 340 genes, which are mainly involved in cellular processes including actin binding, cellular amino acid metabolic process, transmembrane receptor protein serine/threonine kinase signaling, ferrous iron transport, protein transport and localization, cell morphogenesis, and functions associated with endosome membrane and the trans-Golgi network. These genes and associated functions were largely non-overlapping with those altered by Sirt1 knock down. Moreover, we showed that pharmacological inhibition of Sirt2 attenuated oxidant-induced cell toxicity in endothelial cells. These suggest that Sirt2 is functionally important in endothelial cells under oxidative stress, and may have a primarily distinct role as compared to Sirt1. Our results may provide a basis for future studies aiming to dissect the specific signaling pathway(s) that mediates specific Sirt2 functions in endothelial cells.

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Section: Resultssupporting

confidence: 88%

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

Liu

Wang

et al. 2013

IJMS

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“…The relative abundance of microtubule and NOX2 protein subunits in the adult mdx compared with the adult wild type is indirectly supported by the increase in mRNA transcript in both mdx mice and human DMD patients. The presence of the transforming growth factor–β (50) and angiotensin (51) signaling pathways in our network is also notable because of reports that both signaling cascades act to increase microtubule protein content and network density (52, 53) and are activated in human DMD muscle. Furthermore, we and others have shown that inhibition of these pathways is beneficial in both human DMD patients (54) and mdx mice (55).…”

Section: Discussionmentioning

confidence: 84%

Microtubules Underlie Dysfunction in Duchenne Muscular Dystrophy

et al. 2012

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Duchenne muscular dystrophy (DMD) is a fatal X-linked degenerative muscle disease caused by the absence of the microtubule-associated protein dystrophin, which results in a disorganized and denser microtubule cytoskeleton. In addition, mechanotransduction-dependent activation of calcium (Ca2+) and reactive oxygen species (ROS) signaling underpins muscle degeneration in DMD. We show that in muscle from adult mdx mice, a model of DMD, a brief physiologic stretch elicited microtubule-dependent activation of NADPH (reduced-form nicotinamide adenine dinucleotide phosphate) oxidase–dependent production of ROS, termed X-ROS. Further, X-ROS amplified Ca2+ influx through stretch-activated channels in mdx muscle. Consistent with the importance of the microtubules to the dysfunction in mdx muscle, muscle cells with dense microtubule structure, such as those from adult mdx mice or from young wild-type mice treated with Taxol, showed increased X-ROS production and Ca2+ influx, whereas cells with a less dense microtubule network, such as young mdx or adult mdx muscle treated with colchicine or nocodazole, showed little ROS production or Ca2+ influx. In vivo treatments that disrupted the microtubule network or inhibited NADPH oxidase 2 reduced contraction-induced injury in adult mdx mice. Furthermore, transcriptome analysis identified increased expression of X-ROS–related genes in human DMD skeletal muscle. Together, these data show that microtubules are the proximate element responsible for the dysfunction in Ca2+ and ROS signaling in DMD and could be effective therapeutic targets for intervention.

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“…In endothelial cells (ECs), SIRT1 uniquely regulates cell physiology by controlling endothelial homeostasis and vascular functionality by modulating endothelial nitric oxide synthase (eNOS) activity, p53, angiotensin II (Ang II) type 1 receptor (AT1R), and forkhead box O (FOXO) 1. An emerging role of SIRT2 has been described in the hypertension-induced vascular remodeling (65), whereas SIRT3 controls systemic levels of oxidative stress and increases EC survival in response to hypoxia acting on FOXO3/manganese superoxide dismutase (MnSOD) signaling pathway (96,146,195). SIRT4 and SIRT7 aggravate cardiac hypertrophy and negatively affect the proliferation and migration of ECs and vascular smooth muscle cells (VSMCs) (20,199).…”

mentioning

confidence: 99%

SIRT1 and SIRT6 Signaling Pathways in Cardiovascular Disease Protection

D’Onofrio¹,

Servillo²,

Balestrieri³

2018

Antioxidants & Redox Signaling

295

238

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Significance: Oxidative stress represents the common hallmark of pathological conditions associated with cardiovascular disease (CVD), including atherosclerosis, heart failure, hypertension, aging, diabetes, and other vascular system-related diseases. The sirtuin (SIRT) family, comprising seven proteins (SIRT1-SIRT7) sharing a highly conserved nicotinamide adenine dinucleotide (NAD + )-binding catalytic domain, attracted a great attention for the past few years as stress adaptor and epigenetic enzymes involved in the cellular events controlling aging-related disorder, cancer, and CVD. Recent Advances: Among sirtuins, SIRT1 and SIRT6 are the best characterized for their protective roles against inflammation, vascular aging, heart disease, and atherosclerotic plaque development. This latest role has been only recently unveiled for SIRT6. Of interest, in recent years, complex signaling networks controlled by SIRT1 and SIRT6 common to stress resistance, vascular aging, and CVD have emerged. Critical Issues: We provide a comprehensive overview of recent developments on the molecular signaling pathways controlled by SIRT1 and SIRT6, two post-translational modifiers proven to be valuable tools to dampen inflammation and oxidative stress at the cardiovascular level. Future Directions: A deeper understanding of the epigenetic mechanisms through which SIRT1 and SIRT6 act in the signalings responsible for onset and development CVD is a prime scientific endeavor of the upcoming years. Multiple ''omic'' technologies will have widespread implications in understanding such mechanisms, speeding up the achievement of selective and efficient pharmacological modulation of sirtuins for future applications in the prevention and treatment of CVD. Antioxid. Redox Signal. 28, 711-732.

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Angiotensin II induces microtubule reorganization mediated by a deacetylase SIRT2 in endothelial cells

Cited by 42 publications

References 22 publications

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

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

Microtubules Underlie Dysfunction in Duchenne Muscular Dystrophy

SIRT1 and SIRT6 Signaling Pathways in Cardiovascular Disease Protection

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