The up-regulation of hypoxia inducible factor-1α by hypoxic postconditioning reduces hypoxia/reoxygenation-induced injury in heart-derived H9c2 cells / 生理学报
Acta Physiologica Sinica
; (6): 293-300, 2013.
Article
in Zh
| WPRIM
| ID: wpr-333103
Responsible library:
WPRO
ABSTRACT
The aim of the present study was to explore the effects of hypoxic postconditioning (PostC) on heart-derived H9c2 cells injury induced by hypoxia/reoxygenation (H/R) and the expression of hypoxia inducible factor-1α (HIF-1α), and to analyze the relationship between them. Cultured H9c2 cardiac muscle cells were subjected to 3-hour hypoxia and 2-hour reoxygenation to simulate ischemia and reperfusion, or underwent 3 cycles of 5-min reoxygenation and 5-min hypoxia preceding the long reoxygenation to simulate ischemic postconditioning. Cell viability, lactate dehydrogenase (LDH) activity, and caspase-3 activity were detected respectively to investigate the cell injury induced by H/R. The level of HIF-1α mRNA was measured by real-time PCR. Western blot was used to determine HIF-1α protein level. The results showed that postconditioning significantly increased H9c2 cell viability, reduced the activity of LDH and caspase-3. Simultaneously, postconditioning up-regulated the HIF-1α protein level. Moreover, after DMOG, an inhibitor of proline hydroxylase (PHD) which targeted to HIF-1α degradation, was used to stabilize HIF-1α protein level, the reduction of H9c2 cells injury was comparable to that by postconditioning. There was a significant linear positive relationship between HIF-1α protein level and cell viability (r = 0.743, P < 0.01). After HIF-1α gene was silenced by siRNA, the cardio-protective effects of postconditioning was significantly weakened. These data suggest that up-regulation of HIF-1α plays an important role in the cardio-protection of postconditioning.
Full text:
1
Database:
WPRIM
Main subject:
Cell Hypoxia
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Up-Regulation
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Cell Line
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Cell Survival
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Myocytes, Cardiac
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Hypoxia-Inducible Factor 1, alpha Subunit
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Caspase 3
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Ischemic Postconditioning
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Metabolism
Limits:
Animals
Language:
Zh
Journal:
Acta Physiologica Sinica
Year:
2013
Document type:
Article