On the mechanism of the increase in cardiolipin biosynthesis and resynthesis in hepatocytes during rat liver regeneration.
CL (cardiolipin) is a major mitochondrial membrane phospholipid important for the regulation of mitochondrial function. We examined CL de novo biosynthesis and its resynthesis in isolated rat liver hepatocytes prepared 48 h subsequent to two-thirds PHx (partial hepatectomy). The pool size of CL and its de novo biosynthesis from [1,3-(3)H]glycerol were increased 3.3-fold (P<0.05) and 3.1-fold (P<0.05) respectively in hepatocytes prepared from PHx rats compared with sham-operated controls. The reason for the increased CL biosynthesis was a 65% increase (P<0.05) in enzymic activity in PGP-S (phosphatidylglycerolphosphate synthase), a key enzyme in de novo CL biosynthesis. The increase in PGP-S activity was due to a 3-fold increase (P<0.05) of hepatic PGP-S mRNA expression. The increase in de novo CL biosynthesis and pool size corresponded to a 2.3-fold increase (P<0.05) in the amount of [1-14C]linoleic acid incorporated into CL of hepatocytes prepared from PHx rats compared with sham-operated controls, indicating an increase in CL resynthesis. The activity of MLCL-AT (monolysocardiolipin acyltransferase), a rate-limiting enzyme of CL resynthesis, was increased by 43% (P<0.05) in hepatocytes prepared from PHx rats compared with sham-operated controls; this result would explain the increase in [1-14C]linoleic acid incorporation into CL. The increase in MLCL-AT activity was due to an increase in hepatic MLCL-AT protein expression. The results show that CL de novo biosynthesis and its resynthesis are increased during liver regeneration.
Department of Pharmacology and Therapeutics, Center for Research and Treatment of Atherosclerosis, University of Manitoba, Winnipeg, Canada R3E 0T6.
Jennifer
J
Webster
Jenny Y
JY
Jiang
Biao
B
Lu
Fred Y
FY
Xu
William A
WA
Taylor
Mathew
M
Mymin
Manna
M
Zhang
Gerald Y
GY
Minuk
Grant M
GM
Hatch
D000217:Acyltransferases / Q000032:analysis; D000818:Animals; D002308:Cardiolipins / Q000096:biosynthesis*; D006498:Hepatectomy; D022781:Hepatocytes / Q000378:metabolism*; D008115:Liver Regeneration / Q000502:physiology*; D008930:Mitochondria, Liver / Q000201:enzymology; D010743:Phospholipids / Q000032:analysis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011506:Proteins / Q000032:analysis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017855:Transferases (Other Substituted Phosphate Groups) / Q000032:analysis
D002308:Cardiolipins; D010743:Phospholipids; D018809:Proliferating Cell Nuclear Antigen; D011506:Proteins; D012333:RNA, Messenger; D000217:Acyltransferases; C401969:monolysocardiolipin acyltransferase; D017855:Transferases (Other Substituted Phosphate Groups); C020676:CDP-diacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase