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Article: Melatonin ameliorates calcium homeostasis in myocardial and ischemia-reperfusion injury in chronically hypoxic rats

TitleMelatonin ameliorates calcium homeostasis in myocardial and ischemia-reperfusion injury in chronically hypoxic rats
Authors
KeywordsAntioxidant
Calcium
Cardioprotection
Chronic hypoxia
Ischemia
Melatonin
Issue Date2008
PublisherBlackwell Munksgaard. The Journal's web site is located at http://www.blackwellpublishing.com/journals/JPI
Citation
Journal Of Pineal Research, 2008, v. 45 n. 4, p. 373-382 How to Cite?
AbstractChronic hypoxia (CH) leads to the deterioration of myocardial functions with impaired calcium handling in the sarcoplasmic reticulum (SR), which may be mediated by oxidative stress. We hypothesized that administration of antioxidant melatonin would protect against cardiac and ischemia-reperfusion (I/R) injury by ameliorating SR calcium handling. Adult Sprague-Dawley rats that had received a daily injection of melatonin or vehicle were exposed to 10% oxygen for 4 wk. The heart of each rat was then dissected and perfused using a Langendorff apparatus. The ratio of heart-to-body weight, ventricular hypertrophy and hematocrit were increased in the hypoxic rats compared with the normoxic controls. Malondialdehyde levels were also increased in the heart of hypoxic rats and were lowered by the treatment of melatonin. The hearts were subjected to left coronary artery ischemia (30 min) followed by 120-min reperfusion. Lactate dehydrogenase leakage before ischemia, during I/R and infarct size of the isolated perfused hearts were significantly elevated in the vehicle-treated hypoxic rats but not in the melatonin-treated rats. Spectroflurometric studies showed that resting calcium levels and I/R-induced calcium overload in the cardiomyocytes were more significantly altered in the hypoxic rats than the normoxic controls. Also, the hypoxic group had decreased levels of the SR calcium content and reduced amplitude and decay time of electrically induced calcium transients, indicating impaired contractility and SR calcium re-uptake. Moreover, there were reductions in protein expression of calcium handling proteins, markedly shown at the level of SR-Ca2+ ATPase (SERCA) in the heart of hypoxic rats. Melatonin treatment significantly mitigated the calcium handling in the hypoxic rats by preserving SERCA expression. The results suggest that melatonin is cardioprotective against CH-induced myocardial injury by improving calcium handling in the SR of cardiomyocytes via an antioxidant mechanism. © 2008 The Authors.
Persistent Identifierhttp://hdl.handle.net/10722/125089
ISSN
2015 Impact Factor: 9.314
2015 SCImago Journal Rankings: 2.655
ISI Accession Number ID
Funding AgencyGrant Number
Research Grants Council
HKSAR
University Research Council of The University of Hong Kong
Funding Information:

We thank Mr. W. B. Wong for the technical assistance. This study was supported by research grants from Research Grants Council, HKSAR, and the University Research Council of The University of Hong Kong.

References

 

DC FieldValueLanguage
dc.contributor.authorYeung, HMen_HK
dc.contributor.authorHung, MWen_HK
dc.contributor.authorFung, MLen_HK
dc.date.accessioned2010-10-31T11:10:45Z-
dc.date.available2010-10-31T11:10:45Z-
dc.date.issued2008en_HK
dc.identifier.citationJournal Of Pineal Research, 2008, v. 45 n. 4, p. 373-382en_HK
dc.identifier.issn0742-3098en_HK
dc.identifier.urihttp://hdl.handle.net/10722/125089-
dc.description.abstractChronic hypoxia (CH) leads to the deterioration of myocardial functions with impaired calcium handling in the sarcoplasmic reticulum (SR), which may be mediated by oxidative stress. We hypothesized that administration of antioxidant melatonin would protect against cardiac and ischemia-reperfusion (I/R) injury by ameliorating SR calcium handling. Adult Sprague-Dawley rats that had received a daily injection of melatonin or vehicle were exposed to 10% oxygen for 4 wk. The heart of each rat was then dissected and perfused using a Langendorff apparatus. The ratio of heart-to-body weight, ventricular hypertrophy and hematocrit were increased in the hypoxic rats compared with the normoxic controls. Malondialdehyde levels were also increased in the heart of hypoxic rats and were lowered by the treatment of melatonin. The hearts were subjected to left coronary artery ischemia (30 min) followed by 120-min reperfusion. Lactate dehydrogenase leakage before ischemia, during I/R and infarct size of the isolated perfused hearts were significantly elevated in the vehicle-treated hypoxic rats but not in the melatonin-treated rats. Spectroflurometric studies showed that resting calcium levels and I/R-induced calcium overload in the cardiomyocytes were more significantly altered in the hypoxic rats than the normoxic controls. Also, the hypoxic group had decreased levels of the SR calcium content and reduced amplitude and decay time of electrically induced calcium transients, indicating impaired contractility and SR calcium re-uptake. Moreover, there were reductions in protein expression of calcium handling proteins, markedly shown at the level of SR-Ca2+ ATPase (SERCA) in the heart of hypoxic rats. Melatonin treatment significantly mitigated the calcium handling in the hypoxic rats by preserving SERCA expression. The results suggest that melatonin is cardioprotective against CH-induced myocardial injury by improving calcium handling in the SR of cardiomyocytes via an antioxidant mechanism. © 2008 The Authors.en_HK
dc.languageengen_HK
dc.publisherBlackwell Munksgaard. The Journal's web site is located at http://www.blackwellpublishing.com/journals/JPIen_HK
dc.relation.ispartofJournal of Pineal Researchen_HK
dc.rightsThe definitive version is available at www3.interscience.wiley.com-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectAntioxidanten_HK
dc.subjectCalciumen_HK
dc.subjectCardioprotectionen_HK
dc.subjectChronic hypoxiaen_HK
dc.subjectIschemiaen_HK
dc.subjectMelatoninen_HK
dc.subject.meshAnoxia - metabolism-
dc.subject.meshCalcium - metabolism-
dc.subject.meshMelatonin - pharmacology-
dc.subject.meshMyocardial Reperfusion Injury - metabolism-
dc.subject.meshMyocytes, Cardiac - metabolism-
dc.titleMelatonin ameliorates calcium homeostasis in myocardial and ischemia-reperfusion injury in chronically hypoxic ratsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0742-3098&volume=45 &issue=4&spage=373&epage=382&date=2008&atitle=Melatonin+ameliorates+calcium+homeostasis+in+myocardial+and+ischemia-reperfusion+injury+in+chronically+hypoxic+ratsen_HK
dc.identifier.emailFung, ML: fungml@hkucc.hku.hken_HK
dc.identifier.authorityFung, ML=rp00433en_HK
dc.description.naturepostprint-
dc.identifier.doi10.1111/j.1600-079X.2008.00601.xen_HK
dc.identifier.pmid18482339-
dc.identifier.scopuseid_2-s2.0-53749101521en_HK
dc.identifier.hkuros174744en_HK
dc.identifier.hkuros174745-
dc.identifier.hkuros155348-
dc.identifier.hkuros186394-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-53749101521&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume45en_HK
dc.identifier.issue4en_HK
dc.identifier.spage373en_HK
dc.identifier.epage382en_HK
dc.identifier.eissn1600-079X-
dc.identifier.isiWOS:000259951700004-
dc.publisher.placeDenmarken_HK
dc.identifier.scopusauthoridYeung, HM=7102212148en_HK
dc.identifier.scopusauthoridHung, MW=16744402300en_HK
dc.identifier.scopusauthoridFung, ML=7101955092en_HK
dc.identifier.citeulike3401838-

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