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Article: Signal transduction of receptor-mediated antiproliferative action of melatonin on human prostate epithelial cells involves dual activation of Gα s and Gα q proteins

TitleSignal transduction of receptor-mediated antiproliferative action of melatonin on human prostate epithelial cells involves dual activation of Gα s and Gα q proteins
Authors
KeywordsG proteins
melatonin
MTNR1A receptor
p27 Kip1
prostate
Issue Date2010
PublisherBlackwell Munksgaard. The Journal's web site is located at http://www.blackwellpublishing.com/journals/JPI
Citation
Journal Of Pineal Research, 2010, v. 49 n. 3, p. 301-311 How to Cite?
AbstractMelatonin has been shown to inhibit the proliferation of malignant and transformed human prostate epithelial cells by transcriptional up-regulation of p27 Kip1 expression via MTNR1A receptor-mediated activation of protein kinase A (PKA) and protein kinase C (PKC) in parallel. Given that melatonin MTNR1A receptor is a G protein-coupled receptor, this study was conducted to identify the specific G proteins that mediate the antiproliferative action of melatonin on human prostate epithelial cells. In 22Rv1 and RWPE-1 cells, knockdown of either Gα s or Gα q, but not Gα i2 expression by RNA interference, abrogated the effects of melatonin on p27 Kip1 and cell proliferation. Conversely, cellular overexpression of activated mutants of Gα s and Gα q in 22Rv1 and RWPE-1 cells mimicked the effects of melatonin on prostate epithelial cell antiproliferation by increasing p27 Kip1 expression through downstream activation of PKA and PKC in parallel. Moreover, melatonin or 2-iodomelatonin induced elevation of adenosine-3′,5′- cyclic monophosphate (cAMP) in 22Rv1 and RWPE-1 cells. The effects of 2-iodomelatonin on cAMP were blocked by the nonselective MTNR1A/MTNR1B receptor antagonist luzindole but were not affected by the selective MTNR1B receptor antagonist 4-phenyl-2-propionamidotetraline (4-P-PDOT). Furthermore, knockdown of Gα s mitigated the stimulatory effects of 2-iodomelatonin on cAMP. Collectively, the data demonstrated, for the first time, functional coupling of MTNR1A receptor to Gα s in cancerous or transformed human cells expressing endogenous melatonin receptors. Our results also showed that dual activation of Gα s and Gα q proteins is involved in the signal transduction of MTNR1A receptor-mediated antiproliferative action of melatonin on human prostate epithelial cells. © 2010 John Wiley & Sons A/S.
Persistent Identifierhttp://hdl.handle.net/10722/142061
ISSN
2015 Impact Factor: 9.314
2015 SCImago Journal Rankings: 2.655
ISI Accession Number ID
Funding AgencyGrant Number
University of Hong Kong200807176053
Funding Information:

This work was supported by the small project funding scheme (project code: 200807176053) of The University of Hong Kong. Part of the data described in this article were derived from the MPhil thesis of Bo Pang and had been presented at the XI. Congress of the European Biological Rhythms Society.

References

 

DC FieldValueLanguage
dc.contributor.authorShiu, SYWen_HK
dc.contributor.authorPang, Ben_HK
dc.contributor.authorTam, CWen_HK
dc.contributor.authorYao, KMen_HK
dc.date.accessioned2011-10-18T08:15:02Z-
dc.date.available2011-10-18T08:15:02Z-
dc.date.issued2010en_HK
dc.identifier.citationJournal Of Pineal Research, 2010, v. 49 n. 3, p. 301-311en_HK
dc.identifier.issn0742-3098en_HK
dc.identifier.urihttp://hdl.handle.net/10722/142061-
dc.description.abstractMelatonin has been shown to inhibit the proliferation of malignant and transformed human prostate epithelial cells by transcriptional up-regulation of p27 Kip1 expression via MTNR1A receptor-mediated activation of protein kinase A (PKA) and protein kinase C (PKC) in parallel. Given that melatonin MTNR1A receptor is a G protein-coupled receptor, this study was conducted to identify the specific G proteins that mediate the antiproliferative action of melatonin on human prostate epithelial cells. In 22Rv1 and RWPE-1 cells, knockdown of either Gα s or Gα q, but not Gα i2 expression by RNA interference, abrogated the effects of melatonin on p27 Kip1 and cell proliferation. Conversely, cellular overexpression of activated mutants of Gα s and Gα q in 22Rv1 and RWPE-1 cells mimicked the effects of melatonin on prostate epithelial cell antiproliferation by increasing p27 Kip1 expression through downstream activation of PKA and PKC in parallel. Moreover, melatonin or 2-iodomelatonin induced elevation of adenosine-3′,5′- cyclic monophosphate (cAMP) in 22Rv1 and RWPE-1 cells. The effects of 2-iodomelatonin on cAMP were blocked by the nonselective MTNR1A/MTNR1B receptor antagonist luzindole but were not affected by the selective MTNR1B receptor antagonist 4-phenyl-2-propionamidotetraline (4-P-PDOT). Furthermore, knockdown of Gα s mitigated the stimulatory effects of 2-iodomelatonin on cAMP. Collectively, the data demonstrated, for the first time, functional coupling of MTNR1A receptor to Gα s in cancerous or transformed human cells expressing endogenous melatonin receptors. Our results also showed that dual activation of Gα s and Gα q proteins is involved in the signal transduction of MTNR1A receptor-mediated antiproliferative action of melatonin on human prostate epithelial cells. © 2010 John Wiley & Sons A/S.en_HK
dc.languageeng-
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.subjectG proteinsen_HK
dc.subjectmelatoninen_HK
dc.subjectMTNR1A receptoren_HK
dc.subjectp27 Kip1en_HK
dc.subjectprostateen_HK
dc.subject.meshAntioxidants - pharmacology-
dc.subject.meshCell Proliferation - drug effects-
dc.subject.meshGTP-Binding Protein alpha Subunits, Gs - genetics - metabolism-
dc.subject.meshMelatonin - pharmacology-
dc.subject.meshSignal Transduction-
dc.titleSignal transduction of receptor-mediated antiproliferative action of melatonin on human prostate epithelial cells involves dual activation of Gα s and Gα q proteinsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0742-3098&volume=49&issue=3&spage=301&epage=311&date=2010&atitle=Signal+transduction+of+receptor-mediated+antiproliferative+action+of+melatonin+on+human+prostate+epithelial+cells+involves+dual+activation+of+Gαs+and+Gαq+proteins-
dc.identifier.emailShiu, SYW: sywshiu@hkucc.hku.hken_HK
dc.identifier.emailYao, KM: kmyao@hku.hken_HK
dc.identifier.authorityShiu, SYW=rp00384en_HK
dc.identifier.authorityYao, KM=rp00344en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1111/j.1600-079X.2010.00795.xen_HK
dc.identifier.pmid20695976-
dc.identifier.scopuseid_2-s2.0-77956313462en_HK
dc.identifier.hkuros181420-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77956313462&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume49en_HK
dc.identifier.issue3en_HK
dc.identifier.spage301en_HK
dc.identifier.epage311en_HK
dc.identifier.eissn1600-079X-
dc.identifier.isiWOS:000281550300011-
dc.publisher.placeDenmarken_HK
dc.identifier.scopusauthoridShiu, SYW=7005550655en_HK
dc.identifier.scopusauthoridPang, B=37038253900en_HK
dc.identifier.scopusauthoridTam, CW=7201442977en_HK
dc.identifier.scopusauthoridYao, KM=7403234578en_HK
dc.identifier.citeulike7815790-

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