Chronology of patulin-induced alterations in membrane function of cultured renal cells, LLC-PK
- Russell Research Center, Athens, GA (USA)
In a previous study we compared the effects of patulin (PAT) and ouabain, a specific inhibitor of the Na(+)-K+ ATPase, and found significant differences with regard to the kinetics of Na+ influx and K+ efflux, and sulfhydryl reactivity in LLC-PK1 cells. The purpose of the present study was to determine the relationship between Na+ influx, K+ efflux, membrane potential ((3H)tetraphenylphosphonium accumulation), cellular viability (lactate dehydrogenase (LDH) release), and changes in cell morphology (blebs). The effects of PAT are concentration and time dependent. At concentrations of PAT above 10 microM there is a transient increase in intracellular electronegativity (less than 1 hr) followed by a sustained depolarization (greater than 1 hr) which is correlated with complete Na+ influx, K+ efflux, total LDH release, and bleb formation. However, at PAT concentrations of 5-10 microM there is a sustained increased intracellular electronegativity (4-8 hr) which is associated with partial Na+ influx and K+ efflux, no significant LDH release, and relatively few blebs. The hyperpolarizing effect may be a result of increased permeability to K+ relative to Na+. At times and concentrations which result in increased intracellular electronegativity, PAT has no effect on (3H)ouabain binding and thus increased Na+/K+ pump turnover does not seem to be the cause of the transient hyperpolarizing effect of PAT. These results are consistent with the hypothesis that PAT causes alterations in plasma membrane permeability which favor K+ efflux relative to Na+ influx. The toxic effects of PAT are irreversible in LLC-PK1 cells after even short pretreatment with PAT. The primary toxic lesion appears to be at some level other than that involving inhibition of macromolecular synthesis, perhaps the plasma membrane itself.
- OSTI ID:
- 7168378
- Journal Information:
- Toxicology and Applied Pharmacology; (USA), Vol. 102:1; ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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ANTIBIOTICS
BIOLOGICAL EFFECTS
CELL MEMBRANES
PERMEABILITY
OUABAIN
POTASSIUM COMPOUNDS
MEMBRANE TRANSPORT
SODIUM COMPOUNDS
CELL CULTURES
DOSE-RESPONSE RELATIONSHIPS
KIDNEYS
LACTATE DEHYDROGENASE
RABBITS
REAGENTS
SURVIVAL TIME
TIME DEPENDENCE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ALKALI METAL COMPOUNDS
ANIMALS
ANTI-INFECTIVE AGENTS
BODY
CARBOHYDRATES
CARDIAC GLYCOSIDES
CARDIOTONICS
CARDIOVASCULAR AGENTS
CELL CONSTITUENTS
DRUGS
ENZYMES
GLYCOSIDES
HEMIACETAL DEHYDROGENASES
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
MAMMALS
MEMBRANES
ORGANIC COMPOUNDS
ORGANS
OXIDOREDUCTASES
STROPHANTHINS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques