Endotoxin and calcium effect on metabolism.
The effects of calcium and endotoxin were investigated in vivo and in vitro using the A/J, retired white male breeder mouse model. Intravenous administration of increasing calcium doses (3.75, 4.37, and 4.75 mg Ca/g-BW) resulted in increasing serum calcium levels (11.4, 14.4, 15.2, respectively vs. animals not injected, 9.5 mg/dl). Mice injected with E. coli bacterial endotoxin after injection of calcium demonstrated significantly (P less than 0.05) lowered serum calcium concentrations (10.5, 12.1, 12.5, respectively). The magnitude of serum calcium reduction was related to the level just prior to endotoxin administration. Mitochondria were incubated using a Percoll purification step. The effect of pretreating the animal in vivo with calcium, endotoxin or calcium plus endotoxin versus control was investigated in both liver and skeletal muscle. When mitochondria were incubated in medium containing EGTA (free Ca less than 1 X 10(-9)). no significant difference between groups was observed in either (RCR) or mitochondrial calcium content. When mitochondria were incubated in EGTA buffers containing calcium (free Ca approximately 7 X 10(-7) liver, 1 X 10(-7) muscle) significant differences in RCR and mitochondrial calcium content were observed. Liver RCR increased significantly with calcium or endotoxin pretreatment (2.20, 2.43 vs. 1.86). Muscle mitochondrial RCR significantly decreased with calcium administration (5.02 vs. 6.79). Both liver and muscle mitochondrial calcium content significantly decreased (2.54 vs. 27.32, and 6.46 vs. 25.82 nMole Ca/mg mitochondrial protein). Preloading with calcium prevented the decline in mitochondrial calcium content. Findings suggest that the reduction in intramitochondrial calcium content during endotoxemia could be an effector of metabolic derangement specifically through calcium-dependent intramitochondrial enzymes.
Kasden
S E
SE
Department of Surgery, Western Pennsylvania Hospital, Pittsburgh 15224.
Kirkpatrick
J R
JR
D000818:Animals; D002118:Calcium / Q000097:blood / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000097:blood / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism*; D011769:Pyruvate Dehydrogenase (Lipoamide)-Phosphatase / Q000378:metabolism
D008070:Lipopolysaccharides; D011769:Pyruvate Dehydrogenase (Lipoamide)-Phosphatase; D002118:Calcium