| Novel vasoactive intestinal peptide derivatives with improved stability protect rat alveolar L2 cells from cigarette smoke-induced cytotoxicity and apoptosis. | |
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MedLine Citation:
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PMID: 20977915 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Vasoactive intestinal peptide (VIP) has been thought to be a promising candidate for asthma/chronic obstructive pulmonary disease (COPD), and our group previously developed several long-lasting VIP derivatives. The objective of the present study was to clarify the therapeutic potential of new VIP derivatives with improved chemical and metabolic stability. Exposure of rat alveolar L2 cells to cigarette smoke extract (CSE) for 1h led to release of lactate dehydrogenase (LDH) and decreased viability in a CSE concentration-dependent manner. There appeared to be marked induction of apoptosis after CSE exposure, as demonstrated by 59% elevation of caspase-3 activity and TUNEL staining. In contrast, a stabilized VIP derivative, [R(15,20,21), L(17)]-VIP-GRR (IK312532), at a concentration of 10(-7)M, exhibited 71% attenuation of LDH release and 85% decrease of the number of apoptotic cells. In addition to IK312532, new VIP derivatives also showed anti-apoptotic effects against CSE toxicity and marked reduction of nitric oxide production. In terms of cytoprotective effects, [R(15,20,21), L(17), A(24,25), des-N(28)]-VIP-GRR was more effective than VIP and IK312532, possibly due to the improved stability. Thus, the present study is the first to demonstrate that novel stabilized VIP derivatives exert anti-apoptotic and cytoprotective effects on CSE-induced cytotoxicity. |
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Authors:
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Shingen Misaka; Hideyuki Sato; Yosuke Aoki; Takahiro Mizumoto; Satomi Onoue; Shizuo Yamada |
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Publication Detail:
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Type: Journal Article Date: 2010-10-25 |
Journal Detail:
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Title: Peptides Volume: 32 ISSN: 1873-5169 ISO Abbreviation: Peptides Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-21 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8008690 Medline TA: Peptides Country: United States |
Other Details:
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Languages: eng Pagination: 401-7 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Pharmacokinetics and Pharmacodynamics and Global Center of Excellence (COE) Program, School of Pharmaceutical Sciences, University of Shizuoka, 52-1, Yada, Suruga-ku, Shizuoka 422-8526, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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