World Journal of Emergency Medicine ›› 2020, Vol. 11 ›› Issue (4): 246-254.doi: 10.5847/wjem.j.1920-8642.2020.04.007
• Original Article • Previous Articles Next Articles
Rui Zhang1,2,3,4, Meng-yang Xue1,2,3,4, Bao-shan Liu1,2,3,4, Wen-jun Wang1,2,3,4, Xin-hui Fan1,2,3,4, Bo-yuan Zheng1,2,3,4, Qiu-huan Yuan1,2,3,4, Feng Xu1,2,3,4, Jia-li Wang1,2,3,4(
), Yu-guo Chen1,2,3,4()
Received:2019-10-26
Accepted:2020-04-06
Online:2020-10-01
Published:2020-10-01
Contact:
Jia-li Wang,Yu-guo Chen
E-mail:wangjiali_2000@126.com;chen919085@sdu.edu.cn
Rui Zhang, Meng-yang Xue, Bao-shan Liu, Wen-jun Wang, Xin-hui Fan, Bo-yuan Zheng, Qiu-huan Yuan, Feng Xu, Jia-li Wang, Yu-guo Chen. Aldehyde dehydrogenase 2 preserves mitochondrial morphology and attenuates hypoxia/reoxygenation-induced cardiomyocyte injury[J]. World Journal of Emergency Medicine, 2020, 11(4): 246-254.
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URL: http://wjem.com.cn//EN/10.5847/wjem.j.1920-8642.2020.04.007
Figure 1.
ALDH2 activation inhibited OGD/R-induced cell apoptosis. A: representative photographs and quantitative data of apoptotic cardiomyocytes in the control group, the OGD/R (10 hours/1 hour) group, the OGD/R (12 hours/1 hour) group, and the OGD/R (14 hours/1 hour) group by FITC-Annexin V/PI staining using flow cytometry; B: representative photographs and quantitative data of apoptotic cardiomyocytes in the control group, the OGD/R (14 hours/1 hour) group, and the OGD/R (14 hours/1 hour) group+Alda-1 group by TUNEL staining; scale bar: 50 μM; data are means±standard error of mean (SEM); FITC-Annexin V/PI: fluorescein isothiocyanate (FITC)-Annexin V/propidium iodide (PI); TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling; DAPI: 4’,6-diamidino-2-phenylindole; *P<0.05 vs. control group; #P<0.05 vs. OGD/R (14 hours/1 hour) group.
Figure 2.
Both ALDH2 activation and overexpression inhibited OGD/R-induced mitochondrial fission. A: representative photographs and the percentage of cells with mitochondrial fragmentation in the control group, the OGD/R (0.5 hours/1 hour) group, and the OGD/R (4 hours/1 hour) group by mitochondrial staining; scale bar: 25 μM; B: representative photographs and the percentage of cells with mitochondrial fragmentation in the control group, the OGD/R (4 hours/1 hour) group, and the OGD/R (4 hours/1 hour)+Alda-1 group in the concentration range of 20-80 μM by mitochondrial staining; scale bar: 25 μM; C: representative photographs and the percentage of cells with mitochondrial fragmentation in the control group, the OGD/R group, the OGD/R+Ad-ALDH2 group, and the OGD/R+Ad-GFP group; scale bar: 25 μM; Data are means±standard error of mean (SEM). *P<0.05 vs. control group; #P<0.05 vs. OGD/R group.
Figure 3.
ALDH2 suppressed Drp1 phosphorylation at Ser616 but not affected the expression levels of mitochondrial dynamics-regulating proteins. A: representative immunoblots and quantification of the expression levels of Fis1, Mfn1, Mfn2, and Opa1 in the control group and the OGD/R group; B: representative immunoblots and quantification of levels of total Drp1, phosphorylated Drp1 (p-Drp1) at Ser616, total AMPK, and phosphorylated AMPK (p-AMPK) at Thr172 in the control group, the OGD/R group, the OGD/R+Ad-ALDH2 group, and the OGD/R+Ad-GFP group; data are mean±standard error of mean (SEM); *P<0.05 vs. control group; #P<0.05 vs. OGD/R group.
Figure 4.
Schematic illustration of the protective effects of ALDH2 on H/R-induced cardiomyocyte damage. Under H/R, on the one hand, AMPK and Drp1 are activated by phosphorylation which triggers excessive mitochondrial fission, leading to apoptosis; on the other hand, demonstrated by our previous study,[13] PINK/Parkin-dependent mitophagy is activated, contributing to apoptosis; through suppressing either AMPK/Drp1 pathway or PINK/Parkin pathway, ALDH2 could exert cardioprotection effects.
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