Decreasing glycolysis increases sensitivity to mitochondrial inhibition in primary cultures of renal proximal tubule cells |
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Authors: | Richard D Griner Rick G Schnellmann |
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Institution: | (1) Department of Physiology and Pharmacology, College of Veterinary Medicine and Department of Pharmacology and Toxicology, College of Pharmacy, University of Georgia, 30602 Athens, Georgia |
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Abstract: | Summary We have previously shown that shaking the culture plates (SHAKE) of rabbit renal proximal tubule cells (RPTC) to maintain
adequate aeration increased aerobic metabolism and decreased the induction of glycolysis compared to RPTC cultured under standard
conditions (STILL). However, glycolysis in SHAKE RPTC remained elevated compared to glycolysis in proximal tubules in vivo.
In the present study the contribution of culture medium sugar composition and concentration to glycolytic metabolism was assessed
in RPTC. SHAKE and STILL RPTC cultured in 5 mM glucose contained lactate levels equivalent to the respective SHAKE and STILL RPTC cultured in standard culture medium which
contains 17.5 mM glucose. Similarly, the activity of lactate dehydrogenase was unchanged by lowering the medium glucose concentration. Substituting
5 mM galactose for 5 mM glucose in the culture medium significantly reduced the lactate content of both SHAKE and STILL RPTC but had no effect on
lactate dehydrogenase activity. Cell growth was equivalent under all culture conditions. Sensitivity to mitochondrial inhibition
was determined for each culture condition by measuring cell death after exposure to the respiratory inhibitor antimycin A.
The results showed a hierarchy of sensitivity to antimycin A (5 mM galactose SHAKE >5 mM glucose SHAKE >17.5 mM glucose SHAKE = 17.5 mM glucose STILL), which was generally inversely correlated with the level of glycolysis as measured by lactate content (17.5
mM glucose STILL >17.5 mM glucose SHAKE = 5 mM glucose SHAKE >5 mM galactose SHAKE). |
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Keywords: | aerobic metabolism glycolytic metabolism mitochondrial inhibition antimycin A renal proximal tubule cells |
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