Angiotensin II Type-2 Receptor Stimulation Prevents Neural Damage by Transcriptional Activation of Methyl Methanesulfonate Sensitive 2

Mogi, Masaki; Li, Jianmei; Iwanami, Jun; Min, Li‐Juan; Tsukuda, Kana; Iwai, Masaru; Horiuchi, Masatsugu

doi:10.1161/01.hyp.0000229648.67883.f9

Cited by 97 publications

(97 citation statements)

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“…Li et al (2005) reported that AT 2 receptor stimulation enhanced neuronal survival and neurite outgrowth in response to ischemia-induced neuronal injury. We previously showed that AT 2 receptor stimulation enhanced neural differentiation and the repair of damaged DNA by induction of a neural-differentiating factor, methyl methanesulfonate sensitive-2, which is one of the ubiquitin-conjugating enzyme variants (Mogi et al, 2006). In this study, we observed that direct stimulation of the AT 2 receptor enhanced neurite elongation in hippocampal neurons.…”

Section: Discussionmentioning

confidence: 49%

Direct Stimulation of Angiotensin II Type 2 Receptor Enhances Spatial Memory

Jing

Mogi

Sakamoto

et al. 2011

J Cereb Blood Flow Metab

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We examined the possibility that direct stimulation of the angiotensin II type 2 (AT 2 ) receptor by a newly generated direct AT 2 receptor agonist, Compound 21 (C21), enhances cognitive function. Treatment with C21 intraperitoneal injection for 2 weeks significantly enhanced cognitive function evaluated by the Morris water maze test in C57BL6 mice, but this effect was not observed in AT 2 receptor-deficient mice. However, C21-induced cognitive enhancement in C57BL6 mice was attenuated by coadministration of icatibant, a bradykinin B 2 receptor antagonist. Administration of C21 dose dependently increased cerebral blood flow assessed by laser speckle flowmetry and hippocampal field-excitatory postsynaptic potential (f-EPSP) determined by electrophysiological techniques in C57BL6 mice. Furthermore, activation of the AT 2 receptor by C21 promoted neurite outgrowth of cultured hippocampal neurons prepared from fetal transgenic mice expressing green fluorescent protein. Finally, we investigated the pathologic relevance of C21 for spatial learning using an Alzheimer's disease mouse model with intracerebroventricular injection of amyloid-b (1 to 40). We observed that treatment with C21 prevented cognitive decline in this model. These results suggest that a direct AT 2 receptor agonist, C21, enhances cognitive function at least owing to an increase in CBF, enhancement of f-EPSP, and neurite outgrowth in hippocampal neurons.

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Section: Discussionmentioning

confidence: 49%

Direct Stimulation of Angiotensin II Type 2 Receptor Enhances Spatial Memory

Jing

Mogi

Sakamoto

et al. 2011

J Cereb Blood Flow Metab

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“…6 Although it is thought that Ang II does not cross the blood-brain barrier, it has been reported that all RAS components exist in the central nervous system, suggesting that Ang II is produced and functions in the central nervous system. There is no doubt that lowering blood pressure is one of the most recommended therapeutic approaches for the prevention of stroke.…”

Section: Stroke Preventionmentioning

confidence: 99%

“…We also showed that AT 2 receptors enhance neural differentiation and the repair of damaged DNA by induction of the neural differentiating factor MMS2 (methyl methane sulfonate sensitive-2), which is one of the ubiquitin-conjugating enzyme variants. 6 PREVENTION OF METABOLIC SYNDROME-INDUCED DEMENTIA Continuous activation of the brain RAS impairs cognitive function through stimulation of the AT 1 receptor. 23 The ARB candesartan ameliorates impaired cognitive function in mice with type 2 diabetes (KKAy), at least partly, because of increased expression of MMS2 and an improvement in glucose intolerance.…”

Section: Enhancement Of Neural Differentiationmentioning

confidence: 99%

Effects of angiotensin II receptor blockers on dementia

Mogi

Horiuchi

2009

Hypertens Res

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The renin-angiotensin system (RAS) is involved in pathological mechanisms of target organ damage as well as the induction of hypertension; therefore, blockade of the RAS has been expected to prevent cardiovascular and cerebrovascular diseases beyond its antihypertensive effects. In spite of the well-characterized role of angiotensin (Ang) II receptor blockers (ARBs) in preventing the onset and recurrence of stroke, the clinical evidence for an effect of ARBs on dementia has not been definitive. However, preliminary experiments raise the possibility that treatment using ARBs may prevent ischemic brain damage and cognitive impairment. Moreover, recent reports have shown that some ARBs prevent amyloid b deposition in the brain and attenuate cognitive impairment in Alzheimer disease models. Furthermore, recent cohort studies indicate that lower incidence of Alzheimer disease is observed in elderly individuals treated with ARBs. These results indicate a beneficial role for ARBs in cognitive impairment associated with vascular disease, Alzheimer disease, metabolic syndrome and other neurodegenerative diseases. Here, we review the effects of ARBs on the brain with a focus on dementia and future therapeutic approaches for elderly people suffering from disabilities. Hypertension Research (2009) 32, 738-740; doi:10.1038/hr.2009 Keywords: dementia; neuroinflammation; neuroprotective; renin-angiotensin system; stroke INTRODUCTION Dementia is a common but serious health problem. An estimated 33 million elderly persons around the world suffer from dementia, and this number is expected to reach 81.1 million by 2040. 1 Dementia impairs quality of life and is associated with a profound disease burden, morbidity and mortality, not only in patients but also in caregivers. 2,3 Therefore, prevention of dementia is a critical need for advanced countries to address. Life style-related disorders, such as hypertension, diabetes mellitus and obesity have been reported to be related to dementia. For example, large prospective cohort studies indicate that midlife hypertension increases the risk of dementia, 4 suggesting that the blood pressure-lowering effects of antihypertensive drugs may reduce the incidence of dementia. Moreover, recent clinical studies and basic research have suggested several ways in which antihypertensive drugs can prevent target organ damage independently of their antihypertensive effect. In particular, the tissue reninangiotensin system (RAS) (the so-called local RAS) is involved not only in the vasculature but also in the brain. Accumulating evidence from large clinical trials suggests that blockade of the RAS by angiotensin (Ang) II type 1 (AT 1 ) receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors is more effective at inhibiting target organ (such as heart and kidney) damage than other hypertensive agents. 5 Here, we overview the accumulating evidence and suggest possible mechanisms by which ARBs prevent brain damage and dementia.

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“…7 Recently, experimental and clinical studies have reported that cerebral ischemic injury and cognitive function can be ameliorated by inhibition of renin-angiotensin system. [8][9][10] Additionally, brain Ang II is upregulated both in cerebral ischemia and Alzheimer's disease and can be regulated with systemic angiotensin type 1 (AT1) receptor blocker (ARB) treatment. 9,11,12 Thus, Ang II-induced astrocyte senescence may be involved in the pathology of cerebral ischemic injury and age-associated neurodegenerative disease.…”

Section: Introductionmentioning

confidence: 99%

Angiotensin II induces human astrocyte senescence through reactive oxygen species production

et al. 2011

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Angiotensin II (Ang II)-induced astrocyte senescence may be involved in cerebral ischemic injury and age-associated neurodegenerative disease. This study was conducted to determine the roles of reactive oxygen species production in Ang II-induced cellular senescence in cultured human astrocytes. Human astrocytes were stimulated with Ang II either with or without an angiotensin type 1 receptor blocker, CV11974, or an antioxidant, tempol. Application of Ang II to human astrocytes resulted in a concentration-dependent increase in staining for dihydroethidium. Ang II (100 nM for 30 min) increased the translocation of two cytosolic components of NADPH oxidase, p47phox and p67phox, to the cell membrane and formation of the complex of p47phox, p67phox and p22phox. Ang II concentration-dependently induced an increase in b-galactosidase staining. Pretreatment with CV11974 (100 nM) or tempol (3 mM) abolished Ang II-induced astrocyte b-galactosidase staining. Moreover, Ang II significantly upregulated p16 mRNA expression, which was inhibited by pretreatment with CV11974 or tempol. These findings indicate that superoxide production contributes to Ang II-induced astrocyte senescence.

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Angiotensin II Type-2 Receptor Stimulation Prevents Neural Damage by Transcriptional Activation of Methyl Methanesulfonate Sensitive 2

Cited by 97 publications

References 50 publications

Direct Stimulation of Angiotensin II Type 2 Receptor Enhances Spatial Memory

Direct Stimulation of Angiotensin II Type 2 Receptor Enhances Spatial Memory

Effects of angiotensin II receptor blockers on dementia

Angiotensin II induces human astrocyte senescence through reactive oxygen species production

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