On the mechanism of the increase in cardiolipin biosynthesis and resynthesis in hepatocytes during rat liver regeneration

Abstract

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.

Plasma cholinesterase and carboxylesterase activities and nuclear and mitochondrial lipid composition of human placenta associated with maternal exposure to pesticides

“…These changes in lipid content resemble the results of Cascianelli et al [57], who showed an increased sphingomyelin and cholesterol content in nuclear microdomains of regenerated hepatocytes. Interestingly, increased hepatic cardiolipin synthesis, which is presumed to be under the control of transcription factors that regulate mitochondrial biogenesis [58], as well as the pool size of cardiolipin, increased during liver regeneration [59]. Although this study cannot explore the precise mechanisms of the effects observed, our results suggest that the changes in lipid content in the LM and nuclear fractions may be associated with an increase in the trophoblast proliferation rate.…”

Hepatic Protein and Phosphoprotein Signatures of Alcohol-Associated Cirrhosis and Hepatitis

“…33 Our analysis identified that among the proteins down-regulated in AH was a subset involved in the synthesis of cardiolipin (CL) (Table 2), a phospholipid that maintains mitochondria bioenergetics 34 during hepatocyte proliferation and liver regeneration. 35 Figure 7A summarizes the CL biosynthesis pathway and shows the primarily negative correlation between MELD score and enzymes in this pathway, including critical proteins 1acylglycerol-3-phosphate O-acyltransferase 2 (PLCB), protein tyrosine phosphatase mitochondrial 1 (PTPMT1), and hydroxyacyl-CoA dehydrogenase trifunctional complex subunit alpha (ECHA). 36 PLCB and PTPMT1 expression was slightly elevated from AH1 to AH2 but declined from AH2 to AH3 (PLCB being significant), whereas ECHA significantly declined from AH1 to AH3 (Figure 7B).…”

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

“…Subcellular fractions were prepared as previously described [18,21] from murine liver, epidermal fat pad, or RAW 264.7 cells incubated plus or minus LPS. Cells were harvested using PBS and pipetted into test tubes.…”