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postgraduate thesis: Novel mechanisms for STAT regulation in grass carp: signal transduction for glucagon and insulin induction ofSTAT gene expression at the hepatic level

TitleNovel mechanisms for STAT regulation in grass carp: signal transduction for glucagon and insulin induction ofSTAT gene expression at the hepatic level
Authors
Advisors
Advisor(s):Wong, AOL
Issue Date2012
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
Abstract
Glucagon and insulin play important roles in controlling blood glucose and energy metabolism in vertebrate species. Recent studies have identified large cohorts of genes that could be regulated by glucagon and insulin. Signal transducer and activator of transcription (STAT) is a group of signal mediators/inducible transcription factors functionally coupled to class I cytokine receptors through JAK activation. Although the involvement of JAK/STAT pathway has been reported in the physiological actions of insulin and glucagon, the effects of these pancreatic hormones on STAT expression have not been examined. Using grass carp (Ctenopharyngodon idellus) as an animal model, we have cloned the cDNAs for STAT1, STAT3 and STAT5 and confirmed that they are single copy genes in the carp genome. Tissue expression profiling using RT-PCR revealed that the three members of STATs were ubiquitously expressed in various tissues of the grass carp including the liver. Function expression of grass carp STAT1, STAT3 and STAT5 in mammalian cell lines also demonstrated that the STAT proteins of fish origin were all effective in transactivating the target promoters with STAT-binding sites. In grass carp, hepatocyte culture, glucagon and insulin treatment were both effective in increasing STAT1, STAT3 and STAT5 mRNA expression. Using a pharmacological approach, the stimulatory effect of glucagon on transcripts expression of the three forms of STATs were shown to be mediated through activation of the cAMP/PKA, PI3K/AKT and MAPK ( Erk1/2 and JNK) pathways. In the case of insulin stimulation, the PI3K/AKT and p38 MAPK but not JNK pathways were involved in STAT1, STAT3 and STAT5 mRNA up-regulation. Furthermore, insulin-induced STAT3 and STAT5, but not STAT1 mRNA expression, could be blocked by Erk1/2 inactivation, suggesting that the MEK1/2/Erk1/2 pathway might be differentially coupled to gene expression of the individual members of STAT family. These findings provide evidence for first time that glucagon and insulin can regulate STAT1, STAT3 and STAT5 gene expression at the hepatic level in fish model via overlapping and yet distinct signaling mechanisms.
DegreeMaster of Philosophy
SubjectGlucagon.
Insulin.
Gene expression.
Cellular signal transduction.
Carp - Molecular aspects.
Dept/ProgramBiological Sciences

 

DC FieldValueLanguage
dc.contributor.advisorWong, AOL-
dc.contributor.authorPan, Jingfei.-
dc.contributor.author潘竞飞.-
dc.date.issued2012-
dc.description.abstractGlucagon and insulin play important roles in controlling blood glucose and energy metabolism in vertebrate species. Recent studies have identified large cohorts of genes that could be regulated by glucagon and insulin. Signal transducer and activator of transcription (STAT) is a group of signal mediators/inducible transcription factors functionally coupled to class I cytokine receptors through JAK activation. Although the involvement of JAK/STAT pathway has been reported in the physiological actions of insulin and glucagon, the effects of these pancreatic hormones on STAT expression have not been examined. Using grass carp (Ctenopharyngodon idellus) as an animal model, we have cloned the cDNAs for STAT1, STAT3 and STAT5 and confirmed that they are single copy genes in the carp genome. Tissue expression profiling using RT-PCR revealed that the three members of STATs were ubiquitously expressed in various tissues of the grass carp including the liver. Function expression of grass carp STAT1, STAT3 and STAT5 in mammalian cell lines also demonstrated that the STAT proteins of fish origin were all effective in transactivating the target promoters with STAT-binding sites. In grass carp, hepatocyte culture, glucagon and insulin treatment were both effective in increasing STAT1, STAT3 and STAT5 mRNA expression. Using a pharmacological approach, the stimulatory effect of glucagon on transcripts expression of the three forms of STATs were shown to be mediated through activation of the cAMP/PKA, PI3K/AKT and MAPK ( Erk1/2 and JNK) pathways. In the case of insulin stimulation, the PI3K/AKT and p38 MAPK but not JNK pathways were involved in STAT1, STAT3 and STAT5 mRNA up-regulation. Furthermore, insulin-induced STAT3 and STAT5, but not STAT1 mRNA expression, could be blocked by Erk1/2 inactivation, suggesting that the MEK1/2/Erk1/2 pathway might be differentially coupled to gene expression of the individual members of STAT family. These findings provide evidence for first time that glucagon and insulin can regulate STAT1, STAT3 and STAT5 gene expression at the hepatic level in fish model via overlapping and yet distinct signaling mechanisms.-
dc.languageeng-
dc.publisherThe University of Hong Kong (Pokfulam, Hong Kong)-
dc.relation.ispartofHKU Theses Online (HKUTO)-
dc.rightsThe author retains all proprietary rights, (such as patent rights) and the right to use in future works.-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.source.urihttp://hub.hku.hk/bib/B47869756-
dc.subject.lcshGlucagon.-
dc.subject.lcshInsulin.-
dc.subject.lcshGene expression.-
dc.subject.lcshCellular signal transduction.-
dc.subject.lcshCarp - Molecular aspects.-
dc.titleNovel mechanisms for STAT regulation in grass carp: signal transduction for glucagon and insulin induction ofSTAT gene expression at the hepatic level-
dc.typePG_Thesis-
dc.identifier.hkulb4786975-
dc.description.thesisnameMaster of Philosophy-
dc.description.thesislevelmaster's-
dc.description.thesisdisciplineBiological Sciences-
dc.description.naturepublished_or_final_version-
dc.date.hkucongregation2012-

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