Electroacupuncture regulates TRPM7 expression through the trkA/PI3K pathway after cerebral ischemia-reperfusion in rats.
Recently, it was demonstrated that TRPM7 is an essential mediator of anoxia-induced neuronal death. Meanwhile, nerve growth factor (NGF) is known to have survival and neuroprotective effects by interacting with the high affinity neurotrophin receptor, tropomyosin-related kinase A (trkA). In the present study, we found that electroacupuncture (EA) treatment could up-regulate trkA expression after focal cerebral ischemia in rats. At the same time, EA therapy obviously decreased the high expression of TRPM7 induced by ischemia. Using K252a to inhibit trkA, we found that the EA-mediated down-regulation of TRPM7 was significantly suppressed in rats subjected to cerebral ischemia. TrkA can utilize two distinct signaling pathways: the phosphatidylinositol 3-kinase (PI3K) pathway and the extracellular signal-related kinase (ERK) pathway. We found that the effect of EA on TRPM7 was also inhibited by a PI3K inhibitor, while an ERK inhibitor had no effect. Taken together, our findings suggest that EA can reverse the ischemia-induced increase of TRPM7 levels through the trkA-PI3K pathway.
Zhao
Li
L
Department of Neurobiology, Key Laboratory of Neurological Disease of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, PR China.
Wang
Yue
Y
Sun
Ning
N
Liu
Xiaochun
X
Li
Lingli
L
Shi
Jing
J
D000818:Animals; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000201:enzymology / Q000378:metabolism; D015536:Down-Regulation; D015671:Electroacupuncture; D006624:Hippocampus / Q000201:enzymology / Q000378:metabolism; D020925:Hypoxia-Ischemia, Brain / Q000150:complications / Q000201:enzymology / Q000378:metabolism / Q000628:therapy*; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020917:Receptor, trkA / Q000378:metabolism*; D015427:Reperfusion Injury / Q000201:enzymology / Q000209:etiology / Q000378:metabolism / Q000628:therapy*; D015398:Signal Transduction; D050053:TRPM Cation Channels / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
D050053:TRPM Cation Channels; D019869:Phosphatidylinositol 3-Kinases; D020917:Receptor, trkA; C486584:Trpm7 protein, rat