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.
Webster
Jennifer
J
Department of Pharmacology and Therapeutics, Center for Research and Treatment of Atherosclerosis, University of Manitoba, Winnipeg, Canada R3E 0T6.
Jiang
Jenny Y
JY
Lu
Biao
B
Xu
Fred Y
FY
Taylor
William A
WA
Mymin
Mathew
M
Zhang
Manna
M
Minuk
Gerald Y
GY
Hatch
Grant M
GM
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