Cardiolipin synthase-1 mRNA expression does not correlate with endogenous cardiolipin synthase enzyme activity in vitro and in vivo in mammalian lipopolysaccharide models of inflammation.
We examined if lipopolysaccharide (LPS) treatment of mice affected cardiolipin (CL) synthesis. Mice were injected i.p. with LPS, the liver harvested, and CL synthase (CLS) enzyme activity and its mRNA expression examined. Treatment of mice with LPS resulted in a 55% decrease (p < 0.01) in mRNA expression of murine CLS compared to controls, but CLS enzyme activity was unaltered. The pool size of liver CL and other phospholipids were unaltered by LPS treatment. A similar effect was observed in murine epidermal fat pad and in vitro in RAW mouse macrophages and in human HepG2 cells. LPS treatment of HepG2 cells transiently expressing a histidine-tagged human cardiolipin synthase-1 (hCLS1) reduced hCLS1 mRNA and newly synthesized CLS activity indicating that LPS inhibits production of newly synthesized hCLS1 via reduction in hCLS1 mRNA. The results clearly indicate that CLS mRNA levels cannot be correlated with CLS enzyme activity nor CL content in the LPS model of inflammation.
Lu
Biao
B
Department of Medicine, University of California, San Francisco, CA 94121, USA.
Xu
Fred Y
FY
Taylor
William A
WA
Feingold
Kenneth R
KR
Hatch
Grant M
GM
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002308:Cardiolipins / Q000096:biosynthesis* / Q000378:metabolism; D002460:Cell Line; D056945:Hep G2 Cells; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism; D010743:Phospholipids / Q000032:analysis; D012333:RNA, Messenger / Q000096:biosynthesis*; D017855:Transferases (Other Substituted Phosphate Groups) / Q000096:biosynthesis* / Q000235:genetics
C475077:CRLS1 protein, human; D002308:Cardiolipins; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D010743:Phospholipids; D012333:RNA, Messenger; D017855:Transferases (Other Substituted Phosphate Groups); C100091:cardiolipin synthetase