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AMPK differentially alters sulphated glycosaminoglycans under normal and high glucose milieu in proximal tubular cells.
Shrikanth, C. B. and Sanjana, J. and Nandini, C. D. (2020) AMPK differentially alters sulphated glycosaminoglycans under normal and high glucose milieu in proximal tubular cells. Journal of Biochemistry. pp. 1-12.
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J. Biochem. 2020;0(0)1–12.pdf - Published Version Restricted to Registered users only Download (780kB) |
Abstract
Glycosaminoglycans (GAGs) and AMP-activated protein kinase (AMPK) are two critical molecular players involved in cellular homeostasis. Both of them are altered due to hyperglycaemia in the kidney, leading to the pathogenesis of diabetic nephropathy. Here, we have looked into the effect of AMPK modulation on sulphated GAG (sGAG) levels of tubular cells of proximal and distal origin to understand the mechanism of hyperglycaemia-mediated pathogenesis of the diabetic nephropathy. In MDCK cells (distal tubular cell) and NRK-52E (proximal tubular cell), AMPK inhibition resulted in increased sGAG levels under normal glucose conditions characteristically of heparan sulphate class, whereas AMPK activation did not have any effect. High glucose (HG) condition did not alter sGAG levels in MDCK cell despite a decrease in AMPK phosphorylation. Subjecting NRK52E cells to HG milieu significantly decreased sGAG levels more so of chondroitin/dermatan sulphate, which is significantly prevented when HG is co-treated with AMPK activator. Interestingly, knockdown of AMPK by AMPKa1/a2 siRNA showed increased sGAG levels in NRK-52E. Our results suggest that changes in sGAG level, in particular, as a result of AMPK modulation is differentially regulated and is dependent on cell type as well as its physiological status. Furthermore, activation of AMPK is beneficial in preventing the HG-mediated decrease in sGAGs in proximal tubular cells.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | AMPK; diabetic nephropathy; high glucose; sulphated glycosaminoglycans; tubular kidney cells. |
| Subjects: | 600 Technology > 01 Medical sciences > 04 Diabetes Mellitus 600 Technology > 08 Food technology > 16 Nutritive value > 05 Enzymes |
| Divisions: | Molecular Nutrition |
| Depositing User: | Food Sci. & Technol. Information Services |
| Date Deposited: | 01 Jan 2021 07:10 |
| Last Modified: | 01 Jan 2021 07:10 |
| URI: | http://ir.cftri.res.in/id/eprint/14744 |
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