Myocardial ischemia can cause insufficient
oxygen and functional damage to myocardial cells.
Carbonic anhydrase III (CAIII) has been found to be closely related to the abnormality of cardiomyocytes. To investigate the role of CAIII in the apoptosis of myocytes under hypoxic conditions and facilitate the strategy for treating
hypoxia-induced damage, in vitro experiments in H9c2 were employed. The
protein expression of CAIII in H9c2 cells after
hypoxia or normoxia treatment was determined by western blotting and immunohistochemistry. MTT assay was employed for cells viability measurement and LDH release was monitored. The apoptotic cells were observed using immunofluorescence assay, flow cytometric analysis, and TUNEL assay. CAIII-overexpression or -knockdown cells were constructed to determine the role of CAIII in regulating apoptosis-related
proteins caspase-3, Bax, Bcl-2, and anti-apoptosis pathway PI3K/Akt/mTOR. The
mRNA levels of CAIII and genes related to CAIII synthesis including REN, IGHM, APOBEC 3F, and SKOR2 were significantly upregulated in
hypoxia fetal sheep. The expression of CAIII
protein and content of apoptotic H9c2 cells were increased at 1, 3, 6, and 12 h after
hypoxia treatment. Overexpression of CAIII significantly upregulated Bcl2 level and downregulated Bax and
caspase-3 cleavage levels, while its knockdown led to the contrary results. Overexpressed CAIII promoted the HIF-1α level and activated the PI3K/Akt/mTOR pathway, thereby exerting an inhibitory effect on
hypoxia-induced apoptosis. In conclusion, our findings revealed that CAIII could protect cell from
hypoxia-apoptosis of H9c2 cells, in which, activated PI3K/Akt/mTOR signaling pathway may be involved.