| Autor: |
Fernández-Morales JC; Cardiac Signaling Center of MUSC, USC and Clemson, Charleston, SC 29425, USA., Morad M; Cardiac Signaling Center of MUSC, USC and Clemson, Charleston, SC 29425, USA.; Department of Pharmacology, Georgetown University Medical Center, Washington, DC 20057, USA. |
| Jazyk: |
angličtina |
| Zdroj: |
Canadian journal of physiology and pharmacology [Can J Physiol Pharmacol] 2022 Sep 01; Vol. 100 (9), pp. 848-857. Date of Electronic Publication: 2022 Jun 09. |
| DOI: |
10.1139/cjpp-2022-0072 |
| Abstrakt: |
How oxygen is sensed by the heart and what mechanisms mediate its sensing remain poorly understood. As recent reports show that low PO 2 levels are detected by the cardiomyocytes in a few seconds, the rapid and short applications of low levels of oxygen (acute hypoxia), which avoid multiple effects of chronic hypoxia, may be used to probe the oxygen-sensing pathway of the heart. Here, we explored the oxygen-sensing pathway, focusing primarily on cellular surface membrane proteins that were first exposed to low PO 2 . Such studies suggest that acute hypoxia primarily targets the cardiac calcium channels, where either the channel itself or moieties closely associated with it, for instance heme-oxygenase-2 (HO-2) interacting through kinase phosphorylation, signal the α-subunit of the channel to the altered levels of PO 2 . Amino acids 1572-1651, the CaMKII phosphorylation sites (S1487 and S1545), CaM-binding sites (I1624 and Q1625), and Ser1928 of the carboxyl tail of the α-subunit appear to be critical residues that sense oxygen. Future studies on HO-2 knockout mice or CRISPR/Cas9 gene-edited human-induced pluripotent stem-cell-derived cardiomyocytes that reduce CaM-binding affinity are likely to provide deeper insights into the O 2 -sensing mechanisms. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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