Berbamine Protects the Heart From Ischemia/Reperfusion Injury by Maintaining Cytosolic Ca²⁺ Homeostasis and Preventing Calpain Activation

• Zhang Cai-Mei

  Key Laboratory of Stem Cell Biology and Laboratory of Molecular Cardiology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Shanghai Institutes of Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) Key Laboratory of Stem Cell Biology and Laboratory of Molecular Cardiology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Shanghai Institutes of Biological Sciences (SIBS), Chinese Academy of Sciences (CAS)

• Gao Ling

  Key Laboratory of Stem Cell Biology and Laboratory of Molecular Cardiology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Shanghai Institutes of Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) Key Laboratory of Stem Cell Biology and Laboratory of Molecular Cardiology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Shanghai Institutes of Biological Sciences (SIBS), Chinese Academy of Sciences (CAS)

• Zheng Yan-Jun

  Key Laboratory of Stem Cell Biology and Laboratory of Molecular Cardiology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Shanghai Institutes of Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) Key Laboratory of Stem Cell Biology and Laboratory of Molecular Cardiology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Shanghai Institutes of Biological Sciences (SIBS), Chinese Academy of Sciences (CAS)

• Yang Huang-Tian

  Key Laboratory of Stem Cell Biology and Laboratory of Molecular Cardiology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Shanghai Institutes of Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) Shanghai Key Laboratory of Vascular Biology, Ruijin Hospital, SJTUSM Shanghai Stem Cell Institute, SJTUSM Key Laboratory of Stem Cell Biology and Laboratory of Molecular Cardiology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Shanghai Institutes of Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) Shanghai Key Laboratory of Vascular Biology, Ruijin Hospital, SJTUSM Shanghai Stem Cell Institute, SJTUSM

抄録

Background: Berbamine, a natural compound from Barberry, was reported to protect myocardium from ischemia/reperfusion (I/R) injury, but the underlying mechanisms are largely unknown. Methods and Results: Berbamine pretreatment from 10 to 100nmol/L concentration-dependently improved post-ischemic myocardial function. Similar protection was confirmed in isolated cardiomyocytes characterized by the attenuation of I/R-induced intracellular free Ca²⁺ concentration ([Ca²⁺]_i) overloading and the depression of cell shortening and Ca²⁺ transients, which were partially mimicked but not augmented by calpain inhibitor calpeptin and abolished by mitochondrial ATP-sensitive potassium (mitoK_ATP) channel inhibitor 5-hydroxydecanoate (5-HD) and phosphoinositide 3-kinase (PI3K) inhibitor wortmannin. Consistently, I/R-induced increase of calpain activity and decrease of sarcoplasmic reticulum Ca²⁺ ATPase (SERCA2) activity; and protein expression of SERCA2a, desmin, calpastatin and Akt was significantly attenuated by berbamine. In addition, I/R-decreased Akt protein was reversed by calpeptin. Moreover, berbamine further increased I/R-enhanced phosphorylation of Akt and glycogen synthase kinase-3β (GSK3β). These protections were abolished by wortmannin. Furthermore, berbamine significantly attenuated I/R-induced lactate dehydrogenase release, infarct size and contractile dysfunction, and such cardioprotective actions were abolished by wortmannin and 5-HD or mimicked by glycogen synthase kinase-3β (GSK3β) inhibitor SB216763 but without additive effect. Conclusions: These findings suggest that berbamine confers cardioprotection against I/R injury by attenuating [Ca²⁺]_i overloading and preventing calpain activation through the activation of the PI3K-Akt-GSK3β pathway and, subsequently, opening of the mitoK_ATP channel.  (Circ J 2012; 76: 1993–2002)<br>

収録刊行物

• Circulation Journal

  Circulation Journal 76 (8), 1993-2002, 2012

  一般社団法人 日本循環器学会

キーワード

• Berbamine
• Ca²⁺ overloading
• Calpain
• Ischemia/reperfusion
• PI3K-Akt-GSK3β

詳細情報

• CRID: 1390001205102128384
• NII論文ID: 10030505000
• NII書誌ID: AA11591968
• DOI: 10.1253/circj.cj-11-1431
• COI: 1:CAS:528:DC%2BC38Xht1OgtbnN
• ISSN: 13474820
• ISSN: 13469843
• PubMed: 22664727
• Web Site: https://www.jstage.jst.go.jp/article/circj/76/8/76_CJ-11-1431/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2013248132
• 本文言語コード: en
• データソース種別:
  • JaLC
  • Crossref
  • PubMed
  • CiNii Articles
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