Independent role of PP2A and mTORc1 in palmitate induced podocyte death

Biochimie
Sandeep Kumar, Kulbhushan Tikoo

Abstract

Molecular mechanism behind palmitate associated insulin resistance (IR) and podocyte death is not yet fully understood. The present study shows that palmitate treatment induces IR, in human urine derived podocyte-like epithelial cells (HUPECs), which is characterised by decrease in insulin-induced p-AKT, p-GSK3 β and p-ERK1/2. This impairment in insulin signalling prevents insulin induced SIRT 1 expression and deacetylation of p53. Further, palmitate treatment prevents insulin induced phosphorylation of PP2A and FOXO1 but it potentiates the phosphorylation of mTOR at Ser 2448. Interestingly, selective inhibition of PP2A, by Okadaic acid at 5 nM, restored insulin induced phosphorylation of AKT, FOXO1, SIRT1 activity and p53 degradation. However, PP2A inhibition had no effect on mTOR phosphorylation at Ser 2448. On the other hand, partial inhibition of mTORc1, by low dose of Rapamycin (1 nM) also restored phosphorylation of AKT and SIRT1 activity, whereas no significant changes were observed in insulin induced phosphorylation of PP2A after mTORc1 inhibition. To the best of our knowledge this is the first report suggesting independent role of PP2A and mTORc1 in palmitate induced IR and associated podocyte death. Therefore, the bes...Continue Reading

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Citations

Jan 10, 2016·Molecular and Cellular Endocrinology·Sandeep KumarKulbhushan Tikoo
Oct 27, 2017·Current Opinion in Nephrology and Hypertension·Pedro Geraldes
Feb 2, 2019·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Wanning WangLu Cai
Aug 8, 2019·Cell Communication and Signaling : CCS·Xiujuan ZhuJianhua Mao
Aug 24, 2016·The Journal of Biological Chemistry·Kulbhushan TikooVaibhav Shrirang Dhawale
Oct 27, 2017·American Journal of Physiology. Renal Physiology·Honglei GuoYong Gu
Aug 12, 2021·Archives of Physiology and Biochemistry·Ainaz MihanfarMaryam Majidinia
Sep 21, 2021·Experimental and Therapeutic Medicine·Lishi ShaoLi Yang
Dec 5, 2021·Chemical Biology & Drug Design·Joshua NathanaelSulistyo Emantoko Dwi Putra

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