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A soluble receptor for advanced glycation end-products inhibits hypoxia/reoxygenation-induced apoptosis in rat cardiomyocytes via the mitochondrial pathway.

Guo C, Zeng X, Song J, Zhang M, Wang H, Xu X, Du F, Chen B - Int J Mol Sci (2012)

Bottom Line: Compared with H/R alone, sRAGE pretreatment reduced H/R-induced cardiomyocyte apoptosis from 27.9% ± 5.9% to 9.4% ± 0.7% (p < 0.05).In addition, sRAGE treatment significantly inhibited H/R-induced mitochondrial depolarization and mPTP opening, reduced mitochondrial cytochrome c leakage, caspase-3 and caspase-9 activity, and decreased the ratio of Bax to Bcl-2.Therefore, we conclude that the exogenous administration of sRAGE during H/R is involved in cardioprotection by inhibiting apoptosis via the mitochondrial pathway, which, if further confirmed in vivo, may have important clinical implications during H/R.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, Beijing Tian Tan Hospital, Capital Medical University, Beijing 100050, China; E-Mails: songjuan2008@163.com (J.S.); dayanjingzm@sina.com (M.Z.); xuxiaoweittyy@sina.com (X.X.); fhduu@yahoo.com.cn (F.D.); chbux@126.com (B.C.).

ABSTRACT
Severe myocardial dysfunction and tissue damage resulting from ischemia/reperfusion (I/R) is a common clinical scenario in patients with certain types of heart diseases and therapies such as thrombolysis, percutaneous coronary intervention, coronary artery bypass grafting, and cardiac transplantation. The underlining mechanism of endogenous cardiac protection after I/R injury has been a focus of current research. Growing evidences suggests that soluble receptor for advanced glycation end-products (sRAGE) has a cardioprotective effect; however, its role in I/R injury remains unclear. We hypothesized that exogenous administration of sRAGE during hypoxia/reoxygenation (H/R) induces cardioprotection by inhibiting cardiomyocyte apoptosis via multiple signals, involving mitochondrial membrane potential (MMP), the mitochondrial permeability transition pore (mPTP), mitochondrial cytochrome c, caspase-3, Bcl-2 and Bax. Neonatal rat cardiomyocytes underwent hypoxia for 3-h followed by 2-h reoxygenation or were treated with sRAGE for 10 min before H/R. Compared with H/R alone, sRAGE pretreatment reduced H/R-induced cardiomyocyte apoptosis from 27.9% ± 5.9% to 9.4% ± 0.7% (p < 0.05). In addition, sRAGE treatment significantly inhibited H/R-induced mitochondrial depolarization and mPTP opening, reduced mitochondrial cytochrome c leakage, caspase-3 and caspase-9 activity, and decreased the ratio of Bax to Bcl-2. Therefore, we conclude that the exogenous administration of sRAGE during H/R is involved in cardioprotection by inhibiting apoptosis via the mitochondrial pathway, which, if further confirmed in vivo, may have important clinical implications during H/R.

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Related in: MedlinePlus

LDH leakage in medium of cardiomyocytes. LDH content in cell-culture medium was quantified. Con, no treatment; H/R, 3-h hypoxia followed by 2-h reoxygenation; H/R -sRAGE, sRAGE for 10 min, then 3-h hypoxia before 2-h reoxygenation; Con-sRAGE, sRAGE alone. Dose of sRAGE was 900 ng/mL. Data is the mean ± SD (* p < 0.01 compared with the control, # p < 0.01 compared with H/R, n = 8).
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f2-ijms-13-11923: LDH leakage in medium of cardiomyocytes. LDH content in cell-culture medium was quantified. Con, no treatment; H/R, 3-h hypoxia followed by 2-h reoxygenation; H/R -sRAGE, sRAGE for 10 min, then 3-h hypoxia before 2-h reoxygenation; Con-sRAGE, sRAGE alone. Dose of sRAGE was 900 ng/mL. Data is the mean ± SD (* p < 0.01 compared with the control, # p < 0.01 compared with H/R, n = 8).

Mentions: Treatment with H/R increased the amount of cardiomyocyte LDH leakage to 59.6% in comparison with the control group. sRAGE pre-treatment significantly reduced the amount of cardiomyocyte LDH leakage induced by H/R from 159.6% ± 14.7% to 115.6% ± 6.7% (n = 8, p < 0.01). sRAGE alone had no effect on cardiomyocyte LDH leakage (Figure 2).


A soluble receptor for advanced glycation end-products inhibits hypoxia/reoxygenation-induced apoptosis in rat cardiomyocytes via the mitochondrial pathway.

Guo C, Zeng X, Song J, Zhang M, Wang H, Xu X, Du F, Chen B - Int J Mol Sci (2012)

LDH leakage in medium of cardiomyocytes. LDH content in cell-culture medium was quantified. Con, no treatment; H/R, 3-h hypoxia followed by 2-h reoxygenation; H/R -sRAGE, sRAGE for 10 min, then 3-h hypoxia before 2-h reoxygenation; Con-sRAGE, sRAGE alone. Dose of sRAGE was 900 ng/mL. Data is the mean ± SD (* p < 0.01 compared with the control, # p < 0.01 compared with H/R, n = 8).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3472784&req=5

f2-ijms-13-11923: LDH leakage in medium of cardiomyocytes. LDH content in cell-culture medium was quantified. Con, no treatment; H/R, 3-h hypoxia followed by 2-h reoxygenation; H/R -sRAGE, sRAGE for 10 min, then 3-h hypoxia before 2-h reoxygenation; Con-sRAGE, sRAGE alone. Dose of sRAGE was 900 ng/mL. Data is the mean ± SD (* p < 0.01 compared with the control, # p < 0.01 compared with H/R, n = 8).
Mentions: Treatment with H/R increased the amount of cardiomyocyte LDH leakage to 59.6% in comparison with the control group. sRAGE pre-treatment significantly reduced the amount of cardiomyocyte LDH leakage induced by H/R from 159.6% ± 14.7% to 115.6% ± 6.7% (n = 8, p < 0.01). sRAGE alone had no effect on cardiomyocyte LDH leakage (Figure 2).

Bottom Line: Compared with H/R alone, sRAGE pretreatment reduced H/R-induced cardiomyocyte apoptosis from 27.9% ± 5.9% to 9.4% ± 0.7% (p < 0.05).In addition, sRAGE treatment significantly inhibited H/R-induced mitochondrial depolarization and mPTP opening, reduced mitochondrial cytochrome c leakage, caspase-3 and caspase-9 activity, and decreased the ratio of Bax to Bcl-2.Therefore, we conclude that the exogenous administration of sRAGE during H/R is involved in cardioprotection by inhibiting apoptosis via the mitochondrial pathway, which, if further confirmed in vivo, may have important clinical implications during H/R.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, Beijing Tian Tan Hospital, Capital Medical University, Beijing 100050, China; E-Mails: songjuan2008@163.com (J.S.); dayanjingzm@sina.com (M.Z.); xuxiaoweittyy@sina.com (X.X.); fhduu@yahoo.com.cn (F.D.); chbux@126.com (B.C.).

ABSTRACT
Severe myocardial dysfunction and tissue damage resulting from ischemia/reperfusion (I/R) is a common clinical scenario in patients with certain types of heart diseases and therapies such as thrombolysis, percutaneous coronary intervention, coronary artery bypass grafting, and cardiac transplantation. The underlining mechanism of endogenous cardiac protection after I/R injury has been a focus of current research. Growing evidences suggests that soluble receptor for advanced glycation end-products (sRAGE) has a cardioprotective effect; however, its role in I/R injury remains unclear. We hypothesized that exogenous administration of sRAGE during hypoxia/reoxygenation (H/R) induces cardioprotection by inhibiting cardiomyocyte apoptosis via multiple signals, involving mitochondrial membrane potential (MMP), the mitochondrial permeability transition pore (mPTP), mitochondrial cytochrome c, caspase-3, Bcl-2 and Bax. Neonatal rat cardiomyocytes underwent hypoxia for 3-h followed by 2-h reoxygenation or were treated with sRAGE for 10 min before H/R. Compared with H/R alone, sRAGE pretreatment reduced H/R-induced cardiomyocyte apoptosis from 27.9% ± 5.9% to 9.4% ± 0.7% (p < 0.05). In addition, sRAGE treatment significantly inhibited H/R-induced mitochondrial depolarization and mPTP opening, reduced mitochondrial cytochrome c leakage, caspase-3 and caspase-9 activity, and decreased the ratio of Bax to Bcl-2. Therefore, we conclude that the exogenous administration of sRAGE during H/R is involved in cardioprotection by inhibiting apoptosis via the mitochondrial pathway, which, if further confirmed in vivo, may have important clinical implications during H/R.

Show MeSH
Related in: MedlinePlus