A pharmacological activator of AMP-activated protein kinase protects hypoxic neurons in a concentration-dependent manner.
5'adenosine monophosphate-dependent protein kinase (AMPK) is a member of metabolite-sensing kinase family which plays an important role in intracellular energy metabolism, particularly in the hypoxic neurons process. However, the effect of AMPK activation on hypoxic neurons remains controversial. In the present study, we report that the effect of AMPK activation induced by pretreatment with 5-aminoimidazole-4-carboxamide-1-b-4-ribofuranoside (AICAR) in neurons using the hypoxic model in vitro. The level of AMPK activation, the neuronal viability, and the levels of two important cytoskeleton proteins were analyzed during the oxygen deprivation. The AMPK activation was increased with the elevation of the AICAR concentration in hypoxic neurons. Moreover, the AMPK activation induced by AICAR protected neurons against death from hypoxic deprivation and that strongly depended on the extent of the AMPK activation. The AMPK activation at specific range protects hypoxic neurons, but the protective effect of AMPK activation disappeared when the AMPK was over-activated by AICAR. The result from an AMPK inhibitor, Compound C, in hypoxic neurons further proves the neuroprotective effect of AICAR.
Zhang
Xiaolu
X
School of Public Health, Jilin University, Changchun, Jilin, People's Republic of China.
Gao
Rongkun
R
Li
Juan
J
Qi
Yanfei
Y
Song
Xiuling
X
Zhao
Lijing
L
Wang
Hongfang
H
Pu
Yun
Y
Xu
Kun
K
Li
Jinhua
J
D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D015687:Cell Hypoxia; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D003598:Cytoskeletal Proteins / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D012265:Ribonucleotides / Q000494:pharmacology*
D003598:Cytoskeletal Proteins; D020536:Enzyme Activators; D011720:Pyrazoles; D011743:Pyrimidines; D012265:Ribonucleotides; C516138:dorsomorphin; D000620:Aminoimidazole Carboxamide; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide