Carbonic Anhydrase III Attenuates Hypoxia-Induced Apoptosis and Activates PI3K/Akt/mTOR Pathway in H9c2 Cardiomyocyte Cell Line.
Animals
Apoptosis
Apoptosis Regulatory Proteins
/ genetics
Carbonic Anhydrase III
/ genetics
Cell Hypoxia
Cell Line
Fetal Heart
/ enzymology
Gestational Age
Myocytes, Cardiac
/ enzymology
Phosphatidylinositol 3-Kinase
/ metabolism
Proto-Oncogene Proteins c-akt
/ metabolism
Rats
Sheep, Domestic
Signal Transduction
TOR Serine-Threonine Kinases
/ metabolism
Apoptosis
CAIII
H9c2 cells
Hypoxia
PI3K/Akt/mTOR
Journal
Cardiovascular toxicology
ISSN: 1559-0259
Titre abrégé: Cardiovasc Toxicol
Pays: United States
ID NLM: 101135818
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
received:
25
04
2021
accepted:
27
07
2021
pubmed:
14
8
2021
medline:
3
3
2022
entrez:
13
8
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34387844
doi: 10.1007/s12012-021-09683-w
pii: 10.1007/s12012-021-09683-w
doi:
Substances chimiques
Apoptosis Regulatory Proteins
0
mTOR protein, rat
EC 2.7.1.1
Phosphatidylinositol 3-Kinase
EC 2.7.1.137
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Carbonic Anhydrase III
EC 4.2.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
914-926Subventions
Organisme : The effects of hypoxia during pregnancy on fetal cardiovascular development and its related mechanisms
ID : 81560291
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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