| Apelin-13 protects the heart against ischemia-reperfusion injury through inhibition of ER-dependent apoptotic pathways in a time-dependent fashion. | |
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MedLine Citation:
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PMID: 21803944 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Endoplasmic reticulum (ER) stress is activated during and contributes to ischemia/reperfusion (IR) injury. Attenuation of ER stress induced apoptosis protects the heart against IR injury. Using apelin, a ligand to activate the APJ receptor which is known to be cardioprotective, the study was designed to investigate: 1), the time course of changes in IR injury after ER stress; 2), whether apelin infusion protects the heart against IR injury via modulating ER stress dependent apoptosis signaling pathways and 3), how PI3K/Akt, eNOS, AMPK and ERK activation is involved in the protection offered by apelin treatment. The results showed that using an in vivo rat IR model induced by 30 minutes ischemia followed by reperfusion, infarct size (IS) increases from 2 hours of reperfusion (34.85±2.14%) to 12 hours reperfusion (48.98±3.35, P<0.05) which was associated with an abrupt increase in ER stress dependent apoptosis activation, as evidenced by increased CHOP, Caspase-12 and JNK activation (CHOP, 2.49 fold; Caspase-12, 2.09 fold and JNK, 3.38 fold increase. P<0.05, respectively). Administration of apelin at 1ug/Kg not only completely abolished the activation of ER stress induced apoptosis signaling pathways at 2 hours of reperfusion, but also significantly attenuated time-related changes at 24 hours of reperfusion. Using pharmacological inhibition, we also demonstrated that PI3K/Akt, AMPK and ERK activation was involved in protection against IR injury via inhibition of ER stress dependent apoptosis activation. In contrast, although eNOS activation played a role in decreasing IS at 2 hours of reperfusion, it failed to modify either IS or ER stress induced apoptosis signaling pathways at 24 hours after reperfusion. |
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Authors:
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Jianping Tao; Wei Zhu; Yapeng Li; Ping Xin; Jing Li; Mingya Liu; Jingbo Li; Andrew N Redington; Meng Wei |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-7-29 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: - ISSN: 1522-1539 ISO Abbreviation: - Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-8-1 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1. |
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