Expression of cytosolic NADP+-dependent isocitrate dehydrogenase in bovine mammary epithelium

Modulation by regulators of differentiation and metabolic effectors

Wenjing Liu, Anthony V. Capuco, Donato Romagnolo

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The cytosolic NADP+-dependent isocitrate dehydrogenase (IDH1) catalyzes the conversion of isocitrate to a-ketoglutarate in the cytosol, and generates NADPH as a primary source of reducing equivalents for de novo fatty acid synthesis in bovine mammary gland. The enzymatic activity of IDH1 increases dramatically in early lactation in bovine mammary tissue. We hypothesized that the expression of IDH1 in bovine is modulated by regulators of mammary epithelial differentiation. To test this hypothesis, we first examined the changes in IDH1 expression in late pregnancy (-20 days) and at various stages (14, 90, 120, and 240 days) of lactation in bovine mammary tissue. IDH1 mRNA levels increased by 2.3-fold after parturition compared to late pregnancy and remained elevated thereafter. Next, we examined the effects of extracellular matrix and lactogenic hormones on the expression of IDH1 in cultured BME-UV bovine mammary epithelial cells. We found that expression of IDH1 mRNA increased in parallel with β-casein expression 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) inhibitors PD98059 and U0126, and Janus tyrosine kinase 2 (Jak2) inhibitor AG490, suggesting that both MAPK and Jak2 contribute to regulation of IDH1 expression by prolactin. Finally, we report that treatment of BME-UV cells with a-ketoglutarate and palmitic acid reduced IDH1 transcript levels. Taken together, our data suggest that the expression of IDH1 in bovine mammary epithelium is modulated by regulators of differentiation including extracellular matrix and lactogenic hormones as well as metabolic effectors.

Original languageEnglish (US)
Pages (from-to)599-610
Number of pages12
JournalExperimental Biology and Medicine
Volume231
Issue number5
StatePublished - May 2006

Fingerprint

Isocitrate Dehydrogenase
NADP
Prolactin
Breast
Epithelium
Modulation
Messenger RNA
TYK2 Kinase
Extracellular Matrix
Janus Kinase 2
Mitogen-Activated Protein Kinases
Lactation
Hormones
Insulin
Tissue
Palmitic Acid
Pregnancy
Protein Kinase Inhibitors
Caseins
Human Mammary Glands

Keywords

  • Bovine mammary epithelium
  • Differentiation
  • Isocitrate dehydrogenase
  • Lactogenic hormones

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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title = "Expression of cytosolic NADP+-dependent isocitrate dehydrogenase in bovine mammary epithelium: Modulation by regulators of differentiation and metabolic effectors",
abstract = "The cytosolic NADP+-dependent isocitrate dehydrogenase (IDH1) catalyzes the conversion of isocitrate to a-ketoglutarate in the cytosol, and generates NADPH as a primary source of reducing equivalents for de novo fatty acid synthesis in bovine mammary gland. The enzymatic activity of IDH1 increases dramatically in early lactation in bovine mammary tissue. We hypothesized that the expression of IDH1 in bovine is modulated by regulators of mammary epithelial differentiation. To test this hypothesis, we first examined the changes in IDH1 expression in late pregnancy (-20 days) and at various stages (14, 90, 120, and 240 days) of lactation in bovine mammary tissue. IDH1 mRNA levels increased by 2.3-fold after parturition compared to late pregnancy and remained elevated thereafter. Next, we examined the effects of extracellular matrix and lactogenic hormones on the expression of IDH1 in cultured BME-UV bovine mammary epithelial cells. We found that expression of IDH1 mRNA increased in parallel with β-casein expression 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) inhibitors PD98059 and U0126, and Janus tyrosine kinase 2 (Jak2) inhibitor AG490, suggesting that both MAPK and Jak2 contribute to regulation of IDH1 expression by prolactin. Finally, we report that treatment of BME-UV cells with a-ketoglutarate and palmitic acid reduced IDH1 transcript levels. Taken together, our data suggest that the expression of IDH1 in bovine mammary epithelium is modulated by regulators of differentiation including extracellular matrix and lactogenic hormones as well as metabolic effectors.",
keywords = "Bovine mammary epithelium, Differentiation, Isocitrate dehydrogenase, Lactogenic hormones",
author = "Wenjing Liu and Capuco, {Anthony V.} and Donato Romagnolo",
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T2 - Modulation by regulators of differentiation and metabolic effectors

AU - Liu, Wenjing

AU - Capuco, Anthony V.

AU - Romagnolo, Donato

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