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Inhibition of acid-sensing ion channels by amiloride protects rat articular chondrocytes from acid-induced apoptosis via a mitochondrial-mediated pathway.
MedLine Citation:
PMID:  22168390     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
A significant decrease in tissue pH or acidosis is a common feature of numerous diseases, including rheumatoid arthritis (RA). Cartilage homeostasis is profoundly affected by local acidosis in the joints. The diuretic, amiloride, has recently been shown to be neuroprotective in models of cerebral ischemia, a property attributable to the inhibition of acid-sensing ion channels (ASICs) by the drug. However, little known about the effect of amiloride on apoptosis induced by extracellular acid in articular chondrocytes. In this study, we found that amiloride could restrain the acid-induced apoptosis of rat articular chondrocytes in vitro. Primary rat articular chondrocytes were isolated, cultured, and induced to apoptosis by exposure to extracellular solution (pH 6.0),while simultaneously treated with various concentrations of amiloride (50, 100, or 200 μM).The apoptotic rate, mitochondrial function, levels of apoptosis-related gene Bcl-2 family mRNA and activity of caspase-3/9 in chondrocytes were examined. The results showed that amiloride inhibited chondrocyte apoptosis in a dose-dependent manner. Furthermore, amiloride partly restored the levels of mitochondrial membrane potential by regulation of Bcl-2 family gene mRNA expression, and activity of caspase-3/9 in chondrocytes induced by extracellular acid. Our results indicated that amiloride protected against acid-induced apoptosis in rat articular chondrocytes by increasing anti-apoptotic ability and down-regulation of pro-apoptotic factors, thus protecting mitochondrial function.
Authors:
Chao Rong; Feihu Chen; Sheng Jiang; Wei Hu; Fanrong Wu; Tianyi Chen
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-15
Journal Detail:
Title:  Cell biology international     Volume:  -     ISSN:  1095-8355     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9307129     Medline TA:  Cell Biol Int     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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