GS increase mitochondrial function through the SIRT1 pathway in
cardiomyocytes subjected to hypoxia and OGD injuries
Generally, ischemia in the heart can cause mitochondrial dysfunction,
which consequently reduces energy metabolism to cause further cardiac
damage (Kalogeris, Baines, Krenz &
Korthuis, 2012). To further explore the protective effect of GS against
hypoxia and OGD injuries, cell viability, OCR, ATP production,
mitochondrial respiration complexes, and the SIRT1-PGC-1α pathway were
investigated in control, injured model, and GS-treated H9c2 cells. As
shown in Fig. 6A , hypoxia and OGD led to decreases in H9c2 cell
viability, which were slightly recovered by GS. Consistent with current
results, we found that hypoxia induced by Cocl2 for 9 h
significantly diminished the rate of oxygen consumption and ATP
production of H9c2 cells, which were lower during the process of glucose
and oxygen deprivation(Fig. 6B-6C) . GS
pretreatment for 48 h reversed the decreases of OCR and ATP level
induced by hypoxia and OGD in H9c2 cells (Fig. 6B-6C) .
Meanwhile, the levels of five mitochondrial respiratory complexes,
CV-ATP5A, CIII-UQCRC2, CIV-MTCO1, CII-SDHB, and CI-NDUFB8, were
decreased by hypoxia for 9 h, which were obviously recovered by GS at 10
μg/mL ( Fig.
6D-6E) . In addition, Western blot analysis demonstrated that hypoxia
and OGD led to decrease in SIRT1 and PGC-1α levels in H9c2 cells and the
levels of SIRT1 and PGC-1α in GS-pretreated H9c2 cells were higher than
those in the hypoxia- or OGD-induced model group (Fig. 6F-6G) .
Taken together, these results clearly demonstrate the protective effect
of GS to increase mitochondrial function against the hypoxia- or
OGD-induced cardiomyocyte damage through activation of the SIRT1-PGC-1α
pathway.