Maitotoxin-induced liver cell death involving loss of cell ATP following influx of calcium

Journal Article · Sun Oct 01 04:00:00 EDT 1989 · Toxicology and Applied Pharmacology; (USA)

DOI:https://doi.org/10.1016/0041-008X(89)90206-8· OSTI ID:5264714

Kutty, R K; Singh, Y; Santostasi, G; Krishna, G ^[1]

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1. National Heart, Lung, and Blood Institute, Bethesda, MD (USA)

Maitotoxin, one of the most potent marine toxins known, produced cell death in cultures of rat hepatocytes with a TD50 of 80 pM at 24 hr. The cell death, as indicated by a dose- and time-dependent leakage of lactate dehydrogenase (LDH), was also associated with the leakage of (14C)adenine nucleotides from hepatocytes prelabeled with (14C)-adenine. The toxic effect of maitotoxin was completely abolished by the omission of calcium from the culture medium. The cell death induced by maitotoxin increased with increasing concentrations of calcium in the medium. Treatment of hepatocytes with low concentrations of the toxin (less than 0.5 ng/ml) resulted in increases in 45Ca influx into the cells. At higher concentrations of maitotoxin (greater than 1ng/ml), the initial increase in 45Ca influx was followed by the release of the 45Ca from the cells into the medium. Since the 45Ca release paralleled the LDH leakage, the release of calcium was due to cell death. The 45Ca influx, (14C)adenine nucleotide leakage, and LDH leakage were effectively inhibited by verapamil, a calcium channel blocker. Maitotoxin also induced a time- and dose-dependent loss of ATP from hepatocytes, which preceded the (14C)adenine nucleotide and LDH leakage. Thus, it appears that the cell death resulting from maitotoxin treatment is caused by the elevated intracellular calcium, which in turn inhibits mitochondrial oxidative phosphorylation causing depletion of cell ATP. Loss of cell ATP may be the causative event in the maitotoxin-induced cell death.

• OSTI ID: 5264714
• Journal Information: Toxicology and Applied Pharmacology; (USA), Journal Name: Toxicology and Applied Pharmacology; (USA) Vol. 101:1; ISSN TXAPA; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALINE EARTH ISOTOPES
ALKALINE EARTH METALS
ANIMAL CELLS
ANIMALS
ANTIGENS
ATP
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
CALCIUM
CALCIUM 45
CALCIUM ISOTOPES
CARBON 14 COMPOUNDS
CELL CULTURES
CELL KILLING
DAYS LIVING RADIOISOTOPES
DOSE-RESPONSE RELATIONSHIPS
ELEMENTS
ENZYME INHIBITORS
ENZYMES
EVEN-ODD NUCLEI
HEMIACETAL DEHYDROGENASES
INHIBITION
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
LABELLED COMPOUNDS
LACTATE DEHYDROGENASE
LIVER CELLS
MAMMALS
MATERIALS
MEMBRANE PROTEINS
MEMBRANE TRANSPORT
METALS
NUCLEI
NUCLEOTIDES
ORGANIC COMPOUNDS
OXIDOREDUCTASES
PORINS
PROTEINS
RADIOISOTOPES
RATS
RODENTS
SECRETION
SOMATIC CELLS
TIME DEPENDENCE
TOXIC MATERIALS
TOXINS
TRACER TECHNIQUES
VERTEBRATES