Effect of gentamicin on phospholipid metabolism in cultured rabbit proximal tubular cells

Journal Article · Sun Jan 01 04:00:00 EST 1989 · Am. J. Physiol.; (United States)

OSTI ID:6407154

Ramsammy, L S; Josepovitz, C; Lane, B; Kaloyanides, G J

We examined the hypothesis that the accumulation of phospholipid in cells exposed to gentamicin is due to impaired degradation. Experiments were performed in rabbit proximal tubular cells grown in primary culture. Cells exposed to 10(-3) M gentamicin manifested myeloid body formation and a progressive increase in total phospholipid that by day 6 was 44% higher than that of control cells and reflected increases of phosphatidylinositol of 235%, phosphatidylcholine of 60%, phosphatidylethanolamine of 90%, and phosphatidylserine of 55% above control values. Gentamicin impaired the degradation of these phospholipids. The t1/2 of the phospholipid pool labeled with (3H)myoinositol increased 146% from 1.17 (control) to 2.88 days (gentamicin); the t1/2 of the (3H)choline pool increased 34% from 1.77 to 2.38 days; the t1/2 of the (3H)ethanolamine pool increased 57% from 3.14 to 4.93 days; the t1/2 of the (3H) serine pool increased 37% from 6.30 to 8.63 days. Exposure of cells to gentamicin for 2 days also stimulated increased incorporation of (3H)myoinositol (68%) and (3H)ethanolamine (59%) into phospholipid. The data are consistent with the hypothesis that gentamicin inhibits the activity of lysosomal phospholipases that results in the accumulation of phospholipid within the lysosome in the form of myeloid bodies. Increased phospholipid synthesis may represent a compensatory response to the impaired lysosomal degradation of phospholipid. We postulate that the preferential increase of phosphatidylinositol reflects the capacity of the polycationic gentamicin to interact electrostatically with the anionic phosphoinositides and inhibit their turnover.

• Research Organization: State Univ. of New York, Stony Brook (USA)
• OSTI ID: 6407154
• Journal Information: Am. J. Physiol.; (United States), Journal Name: Am. J. Physiol.; (United States) Vol. 256; ISSN AJPHA
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALCOHOLS
AMINES
AMINO ACIDS
AMMONIUM COMPOUNDS
ANIMALS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL HALF-LIFE
BODY
CARBOHYDRATES
CARBOXYLESTERASES
CARBOXYLIC ACIDS
CELL CULTURES
CHOLINE
DRUGS
ENZYMES
ESTERASES
ESTERS
HYDROLASES
HYDROXY ACIDS
HYDROXY COMPOUNDS
INOSITOL
INOSITOLS
ISOTOPE APPLICATIONS
KIDNEYS
KINETICS
LABELLED COMPOUNDS
LIPASE
LIPIDS
LIPOTROPIC FACTORS
MAMMALS
METABOLISM
MONOSACCHARIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
ORGANS
PHOSPHOLIPIDS
PROTEINS
QUATERNARY COMPOUNDS
RABBITS
REACTION KINETICS
SACCHARIDES
SERINE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
TUBULES
VERTEBRATES