Roles of Na⁺/H⁺ exchanger type 1 and intracellular pH in angiotensin II-induced reactive oxygen species generation and podocyte apoptosis

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URI http://shark.lib.kagawa-u.ac.jp/kuir/metadata/27468
Title
Roles of Na⁺/H⁺ exchanger type 1 and intracellular pH in angiotensin II-induced reactive oxygen species generation and podocyte apoptosis
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Description

Abstract

A growing body of evidence suggests that podocyte apoptosis is a major cause of decreased podocyte number, which leads to albuminuria and glomerular injury. The aim of this study was to clarify the molecular mechanisms of angiotensin II (Ang II)-induced apoptosis in cultured mouse podocytes. We examined the effects of Ang II (100 nmol/L) on apoptosis, superoxide anions, and cytosol pH in podocytes. For intracellular pH measurements, image analysis was conducted using confocal laser microscopy after incubation with carboxy-seminaphthorhodafluor-1. Superoxide anions and intracellular pH were elevated with Ang II treatment. Apoptotic cell numbers, as measured by TUNEL staining and caspase 3 activity, were also augmented in the Ang II-treated group. Pre-treatment with olmesartan (100 nmol/L, an Ang II type 1-receptor blocker), apocynin (50 μmol/L, NADPH oxidase inhibitor), or 5-N,N hexamethylene amiloride [30 μmol/L, Na⁺/H⁺ exchanger type 1 (NHE-1) inhibitor] abolished Ang II-induced podocyte apoptosis, whereas NHE-1 mRNA and protein expression was not affected by Ang II treatment. Moreover, Ang II increased NHE-1 phosphorylation. These results suggest that superoxide production, NHE-1 activation, and intracellular alkalization were early features prior to apoptosis in Ang II-treated mouse podocytes, and may offer new insights into the mechanisms responsible for Ang II-induced podocyte

(医博甲585)

Author
著者 劉 雅
著者(ヨミ) リュウ ヤ
著者(別表記) Liu Ya
Publication Title
Journal of Pharmacological Sciences
Publication Title Alternative
J Pharmacol Sci.
Volume
122
Issue
3
Start Page
176
End Page
183
Publisher
Japanese Pharmacological Society
Elsevier
Published Date
2013-06-22
ISSN
1347-8613
NCID
AA11806667
PMID
23800993
Resource Type
Thesis or Dissertation
Language
eng
Relation
PMCID: PMC3792360
Resource URL
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3792360/
Text Version
none
Grant ID
博甲第585号
Grant Date
2014-03-24
Degree Name
博士(医学)
Grantor
香川大学
Set
香川大学
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