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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
Author(s) -
Rong Chao,
Chen FeiHu,
Jiang Sheng,
Hu Wei,
Wu FanRong,
Chen TianYi,
Yuan FengLai
Publication year - 2012
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1042/cbi20110432
Subject(s) - amiloride , acid sensing ion channel , apoptosis , chondrocyte , microbiology and biotechnology , extracellular , chemistry , mitochondrion , pharmacology , biochemistry , in vitro , biology , ion channel , receptor , sodium , organic chemistry
A significant decrease in tissue pH or acidosis is a common feature of numerous diseases, including RA (rheumatoid arthritis). Cartilage homoeostasis is profoundly affected by local acidosis in the joints. The diuretic, amiloride, is neuroprotective in models of cerebral ischaemia, a property attributable to the inhibition of ASICs (acid‐sensing ion channels) by the drug. However, little is known about the effect of amiloride on apoptosis induced by extracellular acid in articular chondrocytes. We have 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 apoptose by exposure to extracellular solution (pH 6.0), while simultaneously treated with 50–200 μM amiloride. Apoptotic rate, mitochondrial function, levels of apoptosis‐related gene Bcl‐2 family mRNA and activity of caspase 3/9 in chondrocytes were examined. 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.