Perturbation of liver microsomal calcium homeostasis by ochratoxin A.
The effect of ochratoxin A on hepatic microsomal calcium sequestration was studied both in vivo and in vitro. The rate of ATP-dependent calcium uptake was inhibited by 42-45% in ochratoxin A intoxicated rats as compared to controls. In the presence of NADPH, addition of ochratoxin A (2.5 to 100 microM) caused a concentration-dependent inhibition of calcium uptake (28-94%) by untreated rat liver microsomes. The rate of NADPH-dependent lipid peroxidation, measured as malondialdehyde formed, was also greatly enhanced by ochratoxin A. Various agents that inhibited ochratoxin A enhanced lipid peroxidation were also able to block the destruction of calcium uptake activity. Lipid peroxidation enhanced by ochratoxin A was also accompanied by leakage of calcium from calcium-loaded microsomes. These results suggest that ochratoxin A disrupts microsomal calcium homeostasis by an impairment of the endoplasmic reticulum membrane probably via enhanced lipid peroxidation.
Khan
S
S
Department of Biochemistry, Memorial University of Newfoundland, St. John's, Canada.
Martin
M
M
Bartsch
H
H
Rahimtula
A D
AD
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009793:Ochratoxins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D009793:Ochratoxins; C025589:ochratoxin A; D002118:Calcium