Differential regulation of GLUT1 and GLUT8 expression by hypoxia in mammary epithelial cells
| Autor: | Theresa L. Wellman, Karen M. Lounsbury, Feng-Qi Zhao, Yong Shao |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
medicine.medical_specialty
GLUT8 Cell Survival Physiology Mammary gland Glucose Transport Proteins Facilitative Biology Mice Mammary Glands Animal Pregnancy Physiology (medical) Internal medicine Lactation Gene expression medicine Transcriptional regulation Animals Hypoxia Cells Cultured Glucose Transporter Type 1 Glucose transporter Epithelial Cells Hypoxia (medical) Hypoxia-Inducible Factor 1 alpha Subunit Up-Regulation Cell biology Mice Inbred C57BL Glucose Endocrinology medicine.anatomical_structure Models Animal biology.protein Pregnancy Animal Cattle Female GLUT1 medicine.symptom Signal Transduction |
| Zdroj: | American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 307:R237-R247 |
| ISSN: | 1522-1490 0363-6119 |
| DOI: | 10.1152/ajpregu.00093.2014 |
| Popis: | Glucose is a major substrate for milk synthesis and is taken up from the blood by mammary epithelial cells (MECs) through facilitative glucose transporters (GLUTs). The expression levels of GLUT1 and GLUT8 are upregulated dramatically in the mammary gland from late pregnancy through early lactation stages. This study aimed to test the hypothesis that this increase in GLUT1 and GLUT8 expression involves hypoxia signaling through hypoxia inducible factor-1α (HIF-1α) in MECs. Mouse mammary glands showed significantly more hypoxia in midpregnancy through early lactation stages compared with in the virgin stage, as stained by the hypoxia marker pimonidazole HCl. Treatment with hypoxia (2% O2) significantly stimulated glucose uptake and GLUT1 mRNA and protein expression, but decreased GLUT8 mRNA expression in bovine MECs. In MECs, hypoxia also increased the levels of HIF-1α protein in the nuclei, and siRNA against HIF-1α completely abolished the hypoxia-induced upregulation of GLUT1, while having no effect on GLUT8 expression. A 5′-RCGTG-3′ core HIF-1α binding sequence was identified 3.7 kb upstream of the bovine GLUT1 gene, and HIF-1α binding to this site was increased during hypoxia. In conclusion, the mammary glands in pregnant and lactating animals are hypoxic, and MECs respond to this hypoxia by increasing GLUT1 expression and glucose uptake through a HIF-1α-dependent mechanism. GLUT8 expression, however, is negatively regulated by hypoxia through a HIF-1α-independent pathway. The regulation of glucose transporters through hypoxia-mediated gene transcription in the mammary gland may provide an important physiological mechanism for MECs to meet the metabolic demands of mammary development and lactation. |
| Databáze: | OpenAIRE |
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