Journal
JOURNAL OF PHARMACOLOGICAL SCIENCES
Volume 122, Issue 3, Pages 176-183Publisher
JAPANESE PHARMACOLOGICAL SOC
DOI: 10.1254/jphs.12291FP
Keywords
angiotensin II; Na+/H+ exchanger type 1 (NHE-1); intracellular pH; apoptosis; podocyte
Categories
Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan [20590253, 22790792]
- Sanju Alumni Research Grant
- Grants-in-Aid for Scientific Research [24591204, 22790792] Funding Source: KAKEN
Ask authors/readers for more resources
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 Aug 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 mu mol/L, NADPH oxidase inhibitor), or 5-N,N hexamethylene amiloride [30 mu mol/L, Na+/H+ exchanger type 1 (NHE-1) inhibitor] abolished Aug II-induced podocyte apoptosis, whereas NHE-1 mRNA and protein expression was not affected by Aug II treatment. Moreover, Aug II increased NHE-1 phosphorylation. These results suggest that superoxide production, NHE-1 activation, and intracellular alkalization were early features prior to apoptosis in Aug II-treated mouse podocytes, and may offer new insights into the mechanisms responsible for Aug II-induced podocyte injury.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available