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Alterations in calcium homeostasis as a possible cause of ochratoxin A nephrotoxicity.
- Source :
-
IARC scientific publications [IARC Sci Publ] 1991 (115), pp. 207-14. - Publication Year :
- 1991
-
Abstract
- Disruption of calcium homeostasis, leading to a sustained increase in cytosolic calcium level, has been associated with cytotoxicity in response to a variety of agents in different cell types. We have observed that a single high dose or multiple lower doses of ochratoxin A administered to rats resulted in an increase in renal endoplasmic reticulum calcium pump activity. The increase was very rapid, being evident within 10 min of ochratoxin A administration and remained elevated for at least 6 h thereafter. Ochratoxin A also decreased renal mitochondrial state-3 respiration and calcium uptake. The latter may lead to an increase in cytosolic calcium level, and the increase in microsomal calcium uptake activity may be an attempt to restore calcium homeostasis. Repeated moderate doses of ochratoxin A led to an eventual decrease in microsomal calcium pump activity, and this could lead to even higher cytosolic calcium levels. Changes in the rate of microsomal calcium uptake correlated with changes in the steady-state levels of the phosphorylated Mg2+/Ca(2+)-ATPase intermediate, indicating that this enzyme is responsible for the calcium pump activity.
- Subjects :
- Animals
Ca(2+) Mg(2+)-ATPase metabolism
Calcium-Transporting ATPases metabolism
Cytosol metabolism
Endoplasmic Reticulum drug effects
Homeostasis
Kidney drug effects
Kidney metabolism
Kidney Diseases metabolism
Male
Microsomes drug effects
Mitochondria drug effects
Mycotoxicosis metabolism
Rats
Rats, Inbred Strains
Calcium metabolism
Calcium-Transporting ATPases drug effects
Kidney Diseases chemically induced
Mycotoxicosis etiology
Ochratoxins toxicity
Subjects
Details
- Language :
- English
- ISSN :
- 0300-5038
- Issue :
- 115
- Database :
- MEDLINE
- Journal :
- IARC scientific publications
- Publication Type :
- Academic Journal
- Accession number :
- 1668170