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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

Cell viability of neonatal rat cardiomyocytes. Cell viability was quantified by the MTT assay. 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 are the mean ± SD of optical density from the MTT assay. (* p < 0.01 compared with the control, # p < 0.01 compared with H/R, n = 8).
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f1-ijms-13-11923: Cell viability of neonatal rat cardiomyocytes. Cell viability was quantified by the MTT assay. 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 are the mean ± SD of optical density from the MTT assay. (* p < 0.01 compared with the control, # p < 0.01 compared with H/R, n = 8).

Mentions: Treatment with H/R reduced the number of viable cells, and sRAGE pre-treatment increased cell viability as determined by the MTT assay. Cell viability in the H/R group accounted for 43.8% of the control group. Compared with the H/R group, sRAGE incubation increased viability from 43.8% ± 10.5% to 96.6% ± 10.1% (n = 8, p < 0.01). sRAGE alone had no effect on cell viability (Figure 1).


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)

Cell viability of neonatal rat cardiomyocytes. Cell viability was quantified by the MTT assay. 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 are the mean ± SD of optical density from the MTT assay. (* 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

f1-ijms-13-11923: Cell viability of neonatal rat cardiomyocytes. Cell viability was quantified by the MTT assay. 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 are the mean ± SD of optical density from the MTT assay. (* p < 0.01 compared with the control, # p < 0.01 compared with H/R, n = 8).
Mentions: Treatment with H/R reduced the number of viable cells, and sRAGE pre-treatment increased cell viability as determined by the MTT assay. Cell viability in the H/R group accounted for 43.8% of the control group. Compared with the H/R group, sRAGE incubation increased viability from 43.8% ± 10.5% to 96.6% ± 10.1% (n = 8, p < 0.01). sRAGE alone had no effect on cell viability (Figure 1).

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