K+ deficiency caused defects in renal tubular cell proliferation, oxidative stress response, tissue repair and tight junction integrity, but enhanced energy production, proteasome function and cellular K+ uptake.
Hypokalemia is a common electrolyte disorder in hospitalized patients and those with chronic diseases and is associated with renal tubular injury. Our recent expression proteomics study revealed changes in levels of several proteins in renal tubular cells during K+ deficiency. However, functional significance and mechanisms underlying such changes remained unclear. The present study, thus, aimed to investigate functional changes of renal tubular cells induced by K+ deficiency. MDCK cells were maintained in normal-K+ (ANK; [K+] = 5.0 mM), Low-K+ (ALK; [K+] = 2.5 mM), or K+-depleted (AKD; [K+] = 0 mM) medium. Cell count and cell death assay showed that ALK and AKD groups had marked decrease in cell proliferation without significant change in cell death. Other functional investigations revealed that AKD cells had significantly increased levels of carbonylated proteins (by OxyBlot assay), impaired tissue repair (by scratch assay), defective tight junction (by Western blotting, immunofluorescence staining and measuring transepithelial electrical resistance), increased intracellular ATP level (by ATP measurement), decreased levels of ubiquitinated proteins (by Western blotting), and increased level of Na+/K+-ATPase (by Western blotting), which was consistent with the increased cellular K+ uptake after K+ repletion. Our findings have shown that AKD caused defects in cell proliferation, oxidative stress response, tissue repair and tight junction integrity, but on the other hand, enhanced energy production, proteasome function and cellular K+ uptake. These findings may shed light onto cellular response to K+ deficiency and better understanding of both pathogenic and compensatory mechanisms in hypokalemic nephropathy.
['Kapincharanon|Chompunoot|C|', 'Thongboonkerd|Visith|V|']
D000818:Animals D016923:Cell Death D049109:Cell Proliferation D004285:Dogs D007008:Hypokalemia D061985:Madin Darby Canine Kidney Cells D018384:Oxidative Stress D046988:Proteasome Endopeptidase Complex D040901:Proteomics D000254:Sodium-Potassium-Exchanging ATPase D019108:Tight Junctions
oxidative stress tight junction proteasome ATP ubiquitin ZO-1