AMPK differentially alters sulphated glycosaminoglycans under normal and high glucose milieu in proximal tubular cells.

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.