ASIC2a overexpression enhances the protective effect of PcTx1 and APETx2 against acidosis-induced articular chondrocyte apoptosis and cytotoxicity.
Acid hydrarthrosis is another important pathological character in rheumatoid arthritis (RA), and acid-sensing ion channel 1a (ASIC1a) plays a destructive role in acidosis-induced articular chondrocyte cytotoxicity. Recently, ASIC2a has been reported to possess neuroprotective effect on acidosis-induced injury of neuronal cells. However, whether ASIC2a has an enhanced effect on the protective effect of blocking ASIC1a and ASIC3 against acid-induced chondrocyte apoptosis is still unclear. The aim of present study was to investigate the chondroprotective effect of ASIC2a with PcTx1 (ASIC1a specific blocker) and APETx2 (ASIC3 specific blocker) on acidosis-induced chondrocyte apoptosis. Our results revealed that acid (pH 6.0) decreased the cell viability and induced apoptosis of articular chondrocytes. PcTx1 and APETx2 combination significantly attenuated acidosis-induced chondrocyte cytotoxicity due to inhibit apoptosis, and this role could be enhanced by ASIC2a overexpression compared with the PcTx1 and APETx2 combination alone group. Moreover, both the [Ca2+]i levels and the levels of phosphorylated ERK1/2 as well as p38 were further reduced in acidosis-induced chondrocytes after ASIC2a overexpression in the presence of PcTx1 and APETx2. Furthermore, ASIC2a overexpression also reduced acid-induced the expression of ASIC1a. In addition, ASIC2a overexpression further promoted the PcTx1 and APETx2-increased levels of type II collagen in acidosis-induced chondrocytes. Taken together, the current data suggested that ASIC2a overexpression might enhance the anti-apoptotic and protective role of PcTx1 and APETx2 against acid-induced rat articular chondrocyte apoptosis by regulating ASIC1a expression and the [Ca2+]i levels and at least in part, suppressing p38 and ERK1/2 MAPK signaling pathways.
['Zhou|Ren-Peng|RP|', 'Ni|Wen-Lin|WL|', 'Dai|Bei-Bei|BB|', 'Wu|Xiao-Shan|XS|', 'Wang|Zhi-Sen|ZS|', 'Xie|Ya-Ya|YY|', 'Wang|Zhi-Qiang|ZQ|', 'Yang|Wei-Jie|WJ|', 'Ge|Jin-Fang|JF|', 'Hu|Wei|W|', 'Chen|Fei-Hu|FH|']
D062646:Acid Sensing Ion Channel Blockers D062565:Acid Sensing Ion Channels D000138:Acidosis D017738:Alkanesulfonic Acids D000818:Animals D017209:Apoptosis D002478:Cells, Cultured D019902:Chondrocytes D003064:Cnidarian Venoms D024043:Collagen Type II D004357:Drug Synergism D005786:Gene Expression Regulation D005822:Genetic Vectors D020935:MAP Kinase Signaling System D009025:Morpholines D010455:Peptides D010957:Plasmids D051381:Rats D013111:Spider Venoms
ASIC2a Articular chondrocytes Apoptosis Rheumatoid arthritis Acidosis Ca(2+)