Hypoxia-inducible Factor-1α (HIF-1α) Protein Diminishes Sodium Glucose Transport 1 (SGLT1) and SGLT2 Protein Expression in Renal Epithelial Tubular Cells (LLC-PK1) under Hypoxia

• Published in: The Journal of biological chemistry 2014-01, Vol.289 (1), p.346-357
• Main Authors: Zapata-Morales, Juan R., Galicia-Cruz, Othir G., Franco, Martha, Martinez y Morales, Flavio
• Format: Article
• Language: English
• Subjects: Animals; Antimutagenic Agents - pharmacology; Cell Biology; Cell Hypoxia - drug effects; Cell Hypoxia - physiology; Cells, Cultured; Cobalt - pharmacology; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; Glucose Transport; GLUT1; Hypoxia; Hypoxia-inducible factor (HIF); Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Kidney Metabolism; Kidney Tubules - cytology; Kidney Tubules - metabolism; Renal Glucose Transporters; Renal Physiology; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; SGLT1; SGLT2; Sodium-Glucose Transporter 1 - biosynthesis; Sodium-Glucose Transporter 1 - genetics; Sodium-Glucose Transporter 2 - biosynthesis; Sodium-Glucose Transporter 2 - genetics; Swine; Time Factors
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M113.526814

In this work, we demonstrated the regulation of glucose transporters by hypoxia inducible factor-1α (HIF-1α) activation in renal epithelial cells. LLC-PK1 monolayers were incubated for 1, 3, 6, or 12 h with 0% or 5% O2 or 300 μm cobalt (CoCl2). We evaluated the effects of hypoxia on the mRNA and protein expression of HIF-1α and of the glucose transporters SGLT1, SGLT2, and GLUT1. The data showed an increase in HIF-1α mRNA and protein expression under the three evaluated conditions (p < 0.05 versus t = 0). An increase in GLUT1 mRNA (12 h) and protein expression (at 3, 6, and 12 h) was observed (p < 0.05 versus t = 0). SGLT1 and SGLT2 mRNA and protein expression decreased under the three evaluated conditions (p < 0.05 versus t = 0). In conclusion, our results suggest a clear decrease in the expression of the glucose transporters SGLT1 and SGLT2 under hypoxic conditions which implies a possible correlation with increased expression of HIF-1α. Hypoxia regulates the transport systems expression in kidney cells. Expression of SGLT1 and SGLT2 is diminished in LLC-PK1 cells exposed to low oxygen concentrations. HIF-1α modified expression of the renal transporters SGLT1 and SGLT2 in LLC-PK1 cells. HIF-1 regulates the expression of glucose transport in LLC-PK1 cells, and this mechanism may be involved in the adaptation of kidney cells under reductions conditions in pO2.