Angiotensin II induces human astrocyte senescence through reactive oxygen species production

Liu, Gang; Hosomi, Naohisa; Hitomi, Hirofumi; Pelisch, Nicolas; Fu, Hua; Masugata, Hisashi; Murao, Koji; Ueno, Masaki; Matsumoto, Masayasu; Nishiyama, Akira

doi:10.1038/hr.2010.269

Cited by 33 publications

(27 citation statements)

References 36 publications

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“…As concerning angiotensin II, it has been documented that in ageing its overexpression caused vascular senescence by mitochondrial and NADPH-dependent superoxide generation [18]. This mechanism was attenuated by mitochondrial electron transport chain or angiotensin type 1 receptor inhibitors [39,40]. Moreover, the infusion in rats of angiotensin II induced microvascular lesions in various vascular beds that resemble arteriolosclerosis [41].…”

Section: Introductionmentioning

confidence: 99%

Ageing and microvasculature

et al. 2014

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A decline in the function of the microvasculature occurs with ageing. An impairment of endothelial properties represents a main aspect of age-related microvascular alterations. Endothelial dysfunction manifests itself through a reduced angiogenic capacity, an aberrant expression of adhesion molecules and an impaired vasodilatory function. Increased expression of adhesion molecules amplifies the interaction with circulating factors and inflammatory cells. The latter occurs in both conduit arteries and resistance arterioles. Age-related impaired function also associates with phenotypic alterations of microvascular cells, such as endothelial cells, smooth muscle cells and pericytes. Age-related morphological changes are in most of cases organ-specific and include microvascular wall thickening and collagen deposition that affect the basement membrane, with the consequent perivascular fibrosis. Data from experimental models indicate that decreased nitric oxide (NO) bioavailability, caused by impaired eNOS activity and NO inactivation, is one of the causes responsible for age-related microvascular endothelial dysfunction. Consequently, vasodilatory responses decline with age in coronary, skeletal, cerebral and vascular beds. Several therapeutic attempts have been suggested to improve microvascular function in age-related end-organ failure, and include the classic anti-atherosclerotic and anti-ischemic treatments, and also new innovative strategies. Change of life style, antioxidant regimens and anti-inflammatory treatments gave the most promising results. Research efforts should persist to fully elucidate the biomolecular basis of age-related microvascular dysfunction in order to better support new therapeutic strategies aimed to improve quality of life and to reduce morbidity and mortality among the elderly patients.

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Section: Introductionmentioning

confidence: 99%

Ageing and microvasculature

et al. 2014

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“…We also reported that aldosterone secretion induced by angiotensin II in astrocytes enhances neuronal damage due to angiotensin II [57]. Moreover, Liu et al showed that angiotensin II induces astrocyte senescence via superoxide production [25]. These findings of astrocyte dysfunction induced by angiotensin II also explain the crucial role of angiotensin II in dysfunction of the neurovascular unit (Figure 1).…”

Section: Effects Of Angiotensin II On Neurovascular Unitmentioning

confidence: 70%

“…On the other hand, Lanz et al showed that angiotensin II induced sustained central nervous system (CNS) inflammation via transforming growth factor- (TGF-) β in an experimental autoimmune encephalomyelitis (EAE) mouse model [24]. Furthermore, angiotensin II induced astrocyte senescence, which is involved in age-associated neurodegenerative disease via superoxide production [25]. In contrast, a centrally active ACE inhibitor, perindopril, was reported to prevent cognitive impairment in chronic central hypoperfusion rats [26] and Alzheimer disease model mice [27].…”

Section: Introductionmentioning

confidence: 99%

Roles of Brain Angiotensin II in Cognitive Function and Dementia

Mogi

Iwanami

Horiuchi

2012

International Journal of Hypertension

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The brain renin-angiotensin system (RAS) has been highlighted as having a pathological role in stroke, dementia, and neurodegenerative disease. Particularly, in dementia, epidemiological studies indicate a preventive effect of RAS blockade on cognitive impairment in Alzheimer disease (AD). Moreover, basic experiments suggest a role of brain angiotensin II in neural injury, neuroinflammation, and cognitive function and that RAS blockade attenuates cognitive impairment in rodent dementia models of AD. Therefore, RAS regulation is expected to have therapeutic potential for AD. Here, we discuss the role of angiotensin II in cognitive impairment and AD. Angiotensin II binds to the type 2 receptor (AT2) and works mainly by binding with the type 1 receptor (AT1). AT2 receptor signaling plays a role in protection against multiple-organ damage. A direct AT2 receptor agonist is now available and is expected to reduce inflammation and oxidative stress and enhance cell differentiation. We and other groups reported that AT2 receptor activation enhances neuronal differentiation and neurite outgrowth in the brain. Here, we also review the effect of the AT2 receptor on cognitive function. RAS modulation may be a new therapeutic option for dementia including AD in the future.

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“…Thus, we speculate that ROS generation and ROSinduced oxidative DNA damage may play a determinant role in TCDD-triggered astrocyte senescence. Coinciding with the notion, ROS have been reported to be crucial mediators of astrocyte senescence under different stressful conditions (Bitto et al, 2010;Liu et al, 2011). In addition, because ROS are involved in mitochondrial dysfunction, changes in mitochondrial biogenesis may also contribute to TCDD-induced premature senescence (Wan et al, 2014).…”

Section: Discussionmentioning

confidence: 97%

2, 3, 7, 8‐Tetrachlorodibenzo‐p‐dioxin induces premature senescence of astrocytes via WNT/β‐catenin signaling and ROS production

Nie

Liang

et al. 2014

J of Applied Toxicology

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2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous environmental contaminant that could exert significant neurotoxicity in the human nervous system. Nevertheless, the molecular mechanism underlying TCDD-mediated neurotoxicity has not been clarified clearly. Herein, we investigated the potential role of TCDD in facilitating premature senescence in astrocytes and the underlying molecular mechanisms. Using the senescence-associated β-galactosidase (SA-β-Gal) assay, we demonstrated that TCDD exposure triggered significant premature senescence of astrocyte cells, which was accompanied by a marked activation of the Wingless and int (WNT)/β-catenin signaling pathway. In addition, TCDD altered the expression of senescence marker proteins, such as p16, p21 and GFAP, which together have been reported to be upregulated in aging astrocytes, in both dose- and time-dependent manners. Further, TCDD led to cell-cycle arrest, F-actin reorganization and the accumulation of cellular reactive oxygen species (ROS). Moreover, the ROS scavenger N-acetylcysteine (NAC) markedly attenuated TCDD-induced ROS production, cellular oxidative damage and astrocyte senescence. Notably, the application of XAV939, an inhibitor of WNT/β-catenin signaling pathway, ameliorated the effect of TCDD on cellular β-catenin level, ROS production, cellular oxidative damage and premature senescence in astrocytes. In summary, our findings indicated that TCDD might induce astrocyte senescence via WNT/β-catenin and ROS-dependent mechanisms.

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Angiotensin II induces human astrocyte senescence through reactive oxygen species production

Cited by 33 publications

References 36 publications

Ageing and microvasculature

Ageing and microvasculature

Roles of Brain Angiotensin II in Cognitive Function and Dementia

2, 3, 7, 8‐Tetrachlorodibenzo‐p‐dioxin induces premature senescence of astrocytes via WNT/β‐catenin signaling and ROS production

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