Baicalin relieves hypoxia-aroused H9c2 cell apoptosis by activating Nrf2/HO-1-mediated HIF1α/BNIP3 pathway.

Publisher: Taylor & Francis Country of Publication: England NLM ID: 101594777 Publication Model: Print Cited Medium: Internet ISSN: 2169-141X (Electronic) Linking ISSN: 21691401 NLM ISO Abbreviation: Artif Cells Nanomed Biotechnol Subsets: MEDLINE

Publication: 2015- : Abingdon, Oxford : Taylor & Francis
Original Publication: London : Informa Healthcare, [2013]-

Apoptosis/*drug effects ; Flavonoids/*pharmacology ; Heme Oxygenase-1/*metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism ; Membrane Proteins/*metabolism ; Mitochondrial Proteins/*metabolism ; NF-E2-Related Factor 2/*metabolism; Animals ; Cell Hypoxia/drug effects ; Cell Line ; Cell Survival/drug effects ; Gene Silencing ; Hypoxia-Inducible Factor 1, alpha Subunit/deficiency ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics ; Myocytes, Cardiac/cytology ; Myocytes, Cardiac/drug effects ; Myocytes, Cardiac/metabolism ; Rats ; Signal Transduction/drug effects

Background: Myocardial ischemia is the main reason for ischemic heart disease. Baicalin is a plant-derived flavonoid with cardio-protective activity. Herein, we tested the influences of baicalin on cardiomyocytes H9c2 apoptosis aroused by hypoxia stimulation. Methods: Firstly, H9c2 cells were subjected to hypoxia and/or baicalin exposure. Cell viability and apoptosis, along with hypoxia-inducible factor 1α (HIF1α) and Bcl-2/adenovirus E1B 19-KDa interacting protein 3 (BNIP3) expressions were tested respectively. Then, si-HIF1α was transfected into H9c2 cells to probe whether up-regulation of HIF1α attended to the influences of baicalin on hypoxia-stimulated H9c2 cells. Finally, the regulatory effect of nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway on HIF1α expression was analyzed. Results: Hypoxia exposure aroused H9c2 cell viability reduction and apoptosis. Baicalin mitigated H9c2 cell viability reduction and apoptosis aroused by hypoxia. Moreover, HIF1α/BNIP3 pathway was further activated by baicalin in hypoxia-exposed H9c2 cells. Silencing HIF1α lowered the functions of baicalin on hypoxia-exposed H9c2 cells. Besides, baicalin enhanced hypoxia-caused activation of Nrf2/HO-1 pathway. Activation of Nrf2/HO-1 pathway was associated with the up-regulation of HIF1α and protective functions of baicalin on hypoxia-exposed H9c2 cells. Conclusion: Baicalin relieved cardiomyocytes H9c2 apoptosis aroused by hypoxia might be achieved through activating Nrf2/HO-1-mediated HIF1α/BNIP3 pathway. Highlights Baicalin mitigates H9c2 cell viability loss and apoptosis aroused by hypoxia; Baicalin activates HIF1a/BNIP3 pathway in hypoxia-exposed H9c2 cells; Silencing HIF1α weakens the influences of baicalin on hypoxia-exposed H9c2 cells; Baicalin promotes Nrf2/HO-1 pathway in hypoxia-exposed H9c2 cells; Promotion of Nrf2/HO-1 pathway is related to the up-regulation of HIF1α.

Update in: Artif Cells Nanomed Biotechnol. 2021 Dec;49(1):676. (PMID: 35112604)

Keywords: Myocardial ischemia; Nrf2/HO-1 pathway; baicalin; cardiomyocytes damage; hypoxia; hypoxia-inducible factor 1α

0 (BNIP3 protein, rat)
0 (Flavonoids)
0 (Hypoxia-Inducible Factor 1, alpha Subunit)
0 (Membrane Proteins)
0 (Mitochondrial Proteins)
0 (NF-E2-Related Factor 2)
347Q89U4M5 (baicalin)
EC 1.14.14.18 (Heme Oxygenase-1)

Date Created: 20190904 Date Completed: 20200204 Latest Revision: 20220203

20240104

10.1080/21691401.2019.1657879

31478766