Gentamicin inhibits degradation of phosphatidylinositol in primary culture of rabbit proximal tubular cells

Conference · Sat Mar 01 04:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5277774

Josepovitz, C; Ramsammy, L; Kalovanides, G J

Gentamicin (G) induces a phosphatidylinositol (PI) enriched phospholipidosis in renal proximal tubular cells, the cause of which has been attributed to inhibition of degradation by lysosomal phospholipases. To test this hypothesis the authors measured the effect of G on phospholipid (PL) metabolism in primary cultures of rabbit proximal tubular cells. Cells incubated in medium containing G (10/sup -5/-10/sup -3/M) accumulated G and PL in a dose and time dependent manner. At the end of 6 days the total PL of cells incubated in G (10/sup -3/M) was 413 +/- 39 nmol/mg protein compared to 288 +/- 13 nmol/mg protein in control cells. The cell content of PI increased 335% above baseline. To assess the role of impaired degradation in the accumulation of PI, cells were incubated in medium containing (/sup 3/H)myoinositol for two days to label the PI pool after which cells were exposed to G (10/sup -3/M) for 2,4 or 6 days and the decline of (/sup 3/H)PI was determined. In control cultures the time for (/sup 3/H)PI to decline 50% was 1.17 days. In cultures exposed to G the t 1/2 was 2.88 days. The authors conclude that rabbit proximal tubular cells grown in primary culture accumulate G and develop a PI-enriched phospholipidosis which is due at least in part to decreased degradation of PI. The results lend strong support to the hypothesis that G-induced phospholipidosis reflects inhibition of lysosomal phospholipases.

• Research Organization: State Univ. of New York, Stony Brook
• OSTI ID: 5277774
• Report Number(s): CONF-8604222-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:3
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
BIOLOGICAL EFFECTS
BODY
CARBOHYDRATES
CARBOXYLESTERASES
CELL CULTURES
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ENZYMES
ESTERASES
ESTERS
HYDROLASES
INHIBITION
INOSITOL
INOSITOLS
ISOTOPE APPLICATIONS
KIDNEYS
LABELLED COMPOUNDS
LIPASE
LIPIDS
MAMMALS
METABOLISM
MONOSACCHARIDES
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
ORGANS
PHOSPHOLIPIDS
RABBITS
SACCHARIDES
TIME DEPENDENCE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
TUBULES
VERTEBRATES