Knockdown of ASIC2a subunit aggravates injury of rat C6 glioma cells in acidosis.
Acid-sensing ion channel 1a (ASIC1a) and 2a (ASIC2a) subunits are widely expressed throughout mammalian central nervous system. Activation of Ca²⁺-permeable ASIC1a homomultimers is largely responsible for acidosis-mediated, glutamate receptorindependent, ischemic neuronal injury. The function of ASIC2a in brain ischemia is less known except that transient global ischemia induces ASIC2a protein expression up-regulation in neurons that survived ischemia. Acidosis is assumed to play a critical role in brain ischemia injury. In the present experiment, rat C6 neuroglioma cells were used to explore the function of ASIC2a. MTT and relative LDH release assay revealed that knockdown of ASIC2a could aggravate the acidosis-induced injury of C6 cells. Through changing extracellular Ca²⁺ concentration and measuring intracellular calcium fluorescence intensity, it was found that aggravated damage was due to toxic Ca²⁺ overload via ASICs mechanisms. The current results indicated that, different from ASIC1a, ASIC2a probably played a protective role against the injury induced by extracellular acidosis in C6 cells.
Department of Biochemical Pharmacology, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Rd, Beijing 100850, China.
Xiao-Yan
XY
Liu
Shu-Zhuo
SZ
Zhang
Xiao-Yun
XY
Ma
Hui
H
Wang
Bao-Hong
BH
Wu
Hong-Liang
HL
Sun
Xin
X
Li
Xiao-Li
XL
Wei
Jian-Quan
JQ
Zheng
D062565:Acid Sensing Ion Channels; D000138:Acidosis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D062626:Degenerin Sodium Channels; D053503:Epithelial Sodium Channels / Q000235:genetics* / Q000378:metabolism; D005910:Glioma; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D034622:RNA Interference; D051381:Rats; D014162:Transfection
D062565:Acid Sensing Ion Channels; C568425:Asic2 protein, rat; D062626:Degenerin Sodium Channels; D053503:Epithelial Sodium Channels; D009419:Nerve Tissue Proteins; D002118:Calcium