Regulation of Cytosolic NADP+-Dependent Isocitrate Dehydrogenase Expression

Persistent Link:
http://hdl.handle.net/10150/193861
Title:
Regulation of Cytosolic NADP+-Dependent Isocitrate Dehydrogenase Expression
Author:
Liu, Wenjing
Issue Date:
2006
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
The long-range goal of this project is to investigate the mechanisms involved in the regulation of the cytosolic NADP+- dependent isocitrate dehydrogenase (IDH1) expression. This dissertation focuses on the central hypothesis that the expression of IDH1 is modulated by regulators of mammary epithelial differentiation and metabolic effectors in bovine mammary epithelium. To test this hypothesis, we examined the mRNA expression of IDH1 in late pregnancy and at various stages of lactation in bovine mammary tissue and demonstrated that IDH1 mRNA levels increased by 2.3 fold after parturition compared to late pregnancy and remained constant thereafter. Then, we investigated the effects of extracellular matrix and lactogenic hormones on the expression of IDH1 in cultured BME-UV bovine mammary epithelial cells. We found that the expression of IDH1 mRNA increased in parallel with beta-casein expression during cell differentiation induced by extracellular matrix. Fetal calf serum and insulin repressed, whereas prolactin stimulated the expression of IDH1 mRNA in a dose-dependent fashion. The inhibitory effects of insulin on IDH1 mRNA levels were antagonized by cotreatment with prolactin. In contrast, treatment with prolactin in the presence of extracellular matrix further increased IDH1 mRNA and protein accumulation. Prolactin-induced IDH1 expression was inhibited by the mitogen-activated protein kinase (MAPK) pathway inhibitors PD98059 and U0126, and Janus tyrosine kinase 2 (JAK2), suggesting that both MAPK and JAK2 contribute to regulation of IDH1 expression by prolactin. Moreover, we demonstrated that the levels of IDH1 transcripts were reduced when BME-UV cells were treated with alpha-ketoglutarate and palmitic acid. Finally, we report that the trans-10, cis-12 CLA, but not cis-9, trans-11 CLA isomer, repress prolactin-induced IDH1 mRNA as well as protein accumulation. Taken together, these data suggest that the expression of IDH1 is modulated by regulators of mammary epithelial differentiation and metabolic effectors including lactogenic hormones, extracellular matrix and nutrients.
Type:
text; Electronic Dissertation
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Nutritional Sciences; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Romagnolo, Donato F.
Committee Chair:
Romagnolo, Donato F.

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleRegulation of Cytosolic NADP+-Dependent Isocitrate Dehydrogenase Expressionen_US
dc.creatorLiu, Wenjingen_US
dc.contributor.authorLiu, Wenjingen_US
dc.date.issued2006en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractThe long-range goal of this project is to investigate the mechanisms involved in the regulation of the cytosolic NADP+- dependent isocitrate dehydrogenase (IDH1) expression. This dissertation focuses on the central hypothesis that the expression of IDH1 is modulated by regulators of mammary epithelial differentiation and metabolic effectors in bovine mammary epithelium. To test this hypothesis, we examined the mRNA expression of IDH1 in late pregnancy and at various stages of lactation in bovine mammary tissue and demonstrated that IDH1 mRNA levels increased by 2.3 fold after parturition compared to late pregnancy and remained constant thereafter. Then, we investigated the effects of extracellular matrix and lactogenic hormones on the expression of IDH1 in cultured BME-UV bovine mammary epithelial cells. We found that the expression of IDH1 mRNA increased in parallel with beta-casein expression during cell differentiation induced by extracellular matrix. Fetal calf serum and insulin repressed, whereas prolactin stimulated the expression of IDH1 mRNA in a dose-dependent fashion. The inhibitory effects of insulin on IDH1 mRNA levels were antagonized by cotreatment with prolactin. In contrast, treatment with prolactin in the presence of extracellular matrix further increased IDH1 mRNA and protein accumulation. Prolactin-induced IDH1 expression was inhibited by the mitogen-activated protein kinase (MAPK) pathway inhibitors PD98059 and U0126, and Janus tyrosine kinase 2 (JAK2), suggesting that both MAPK and JAK2 contribute to regulation of IDH1 expression by prolactin. Moreover, we demonstrated that the levels of IDH1 transcripts were reduced when BME-UV cells were treated with alpha-ketoglutarate and palmitic acid. Finally, we report that the trans-10, cis-12 CLA, but not cis-9, trans-11 CLA isomer, repress prolactin-induced IDH1 mRNA as well as protein accumulation. Taken together, these data suggest that the expression of IDH1 is modulated by regulators of mammary epithelial differentiation and metabolic effectors including lactogenic hormones, extracellular matrix and nutrients.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineNutritional Sciencesen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorRomagnolo, Donato F.en_US
dc.contributor.chairRomagnolo, Donato F.en_US
dc.contributor.committeememberMeuillet, Emmanuelleen_US
dc.contributor.committeememberAllen, Ronald E.en_US
dc.contributor.committeememberGoing, Scotten_US
dc.contributor.committeememberHowell, Wandaen_US
dc.identifier.proquest1669en_US
dc.identifier.oclc659746279en_US
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