Susovon Bayen1, Supriya Saini1, Priya Gaur1, Arul Joseph Duraisamy1, Alpesh Kumar Sharma1, Karan Pal1, Praveen Vats2, Shashi Bala Singh3. 1. Endocrinology & Metabolism Division, Defence Institute of Physiology and Allied Sciences, Lucknow Road, Timarpur, Delhi, 110054, India. 2. Endocrinology & Metabolism Division, Defence Institute of Physiology and Allied Sciences, Lucknow Road, Timarpur, Delhi, 110054, India. vatsp2001@rediffmail.com. 3. Department of Applied Physiology, Defence Institute of Physiology and Allied Sciences, Lucknow Road, Timarpur, Delhi, 110054, India.
Abstract
PURPOSE: High-altitude (HA) environment causes changes in cellular metabolism among unacclimatized humans. Previous studies have revealed that insulin-dependent activation of protein kinase B (Akt) regulates metabolic processes via discrete transcriptional effectors. Moreover, protein arginine methyltransferase (PRMT)1-dependent arginine modification of forkhead box other (FoxO)1 protein interferes with Akt-dependent phosphorylation. The present study was undertaken to test the involvement of PRMT1 on FoxO1 activation during hypobaric hypoxia (HH) exposure in rat model. METHODS: Samples were obtained from normoxia control (NC) and HH-exposed (H) rats, subdivided according to the duration of HH exposure. To explore the specific role played by PRMT1 during HH exposure, samples from 1d pair-fed (PF) NC, 1d acute hypoxia-exposed (AH) placebo-treated, and 1d AH TC-E-5003-treated rats were investigated. Quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) was performed to determine expressions of glycolytic, gluconeogenic enzymes, and insulin response regulating genes. Immuno-blot and enzyme linked immunosorbent assay (ELISA) were used for insulin response regulating proteins. Nuclear translocation of FoxO1 was analyzed using deoxyribonucleic acid (DNA)-binding ELISA kit. RESULTS: We observed HH-induced increase in glycolytic enzyme expressions in hepatic tissue unlike hypothalamic tissue. PRMT1 expression increased during HH exposure, causing insulin resistance and resulting increase in FoxO1 nuclear translocation, leading to hyperglycemia. Conversely, PRMT1 inhibitor treatment promoted inhibition of FoxO1 activity and increase in glucose uptake during HH exposure leading to reduction in blood-glucose and hepatic glycogen levels. CONCLUSIONS: PRMT1 might have a potential importance as a therapeutic target for the treatment of HH-induced maladies.
PURPOSE: High-altitude (HA) environment causes changes in cellular metabolism among unacclimatized humans. Previous studies have revealed that insulin-dependent activation of protein kinase B (Akt) regulates metabolic processes via discrete transcriptional effectors. Moreover, protein arginine methyltransferase (PRMT)1-dependent arginine modification of forkhead box other (FoxO)1 protein interferes with Akt-dependent phosphorylation. The present study was undertaken to test the involvement of PRMT1 on FoxO1 activation during hypobaric hypoxia (HH) exposure in rat model. METHODS: Samples were obtained from normoxia control (NC) and HH-exposed (H) rats, subdivided according to the duration of HH exposure. To explore the specific role played by PRMT1 during HH exposure, samples from 1d pair-fed (PF) NC, 1d acute hypoxia-exposed (AH) placebo-treated, and 1d AH TC-E-5003-treated rats were investigated. Quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) was performed to determine expressions of glycolytic, gluconeogenic enzymes, and insulin response regulating genes. Immuno-blot and enzyme linked immunosorbent assay (ELISA) were used for insulin response regulating proteins. Nuclear translocation of FoxO1 was analyzed using deoxyribonucleic acid (DNA)-binding ELISA kit. RESULTS: We observed HH-induced increase in glycolytic enzyme expressions in hepatic tissue unlike hypothalamic tissue. PRMT1 expression increased during HH exposure, causing insulin resistance and resulting increase in FoxO1 nuclear translocation, leading to hyperglycemia. Conversely, PRMT1 inhibitor treatment promoted inhibition of FoxO1 activity and increase in glucose uptake during HH exposure leading to reduction in blood-glucose and hepatic glycogen levels. CONCLUSIONS:PRMT1 might have a potential importance as a therapeutic target for the treatment of HH-induced maladies.
Entities:
Keywords:
Fork head box protein; Hyperglycemia; Hypobaric hypoxia; Insulin resistance; Protein arginine methyltransferase 1; Protein kinase B
Authors: K D Niswender; C Postic; T L Jetton; B D Bennett; D W Piston; S Efrat; M A Magnuson Journal: J Biol Chem Date: 1997-09-05 Impact factor: 5.157
Authors: Cullen M Taniguchi; Elizabeth C Finger; Adam J Krieg; Colleen Wu; Anh N Diep; Edward L LaGory; Kevin Wei; Lisa M McGinnis; Jenny Yuan; Calvin J Kuo; Amato J Giaccia Journal: Nat Med Date: 2013-09-15 Impact factor: 53.440