Angiotensin-mediated phosphatidylcholine hydrolysis and protein kinase C activation in mesangial cells.
Angiotensin II (ANG II) in mesangial cells (MC) promotes phosphatidylinositol (PI) hydrolysis resulting in diacylglycerol (DAG)-mediated increases in protein kinase C (PKC) activity. The paucity of MC inositol lipid prompted us to consider whether phosphatidylcholine (PC) could sustain DAG formation. ANG II released choline and increased phosphatidylethanol (PEt) via PC-phospholipase D (PC-PLD). ANG II also stimulated phosphorylcholine consequent to PC-phospholipase C (PC-PLC) activation. ANG II-mediated PC hydrolysis augmented DAG for 30 min. PC breakdown was influenced by extracellular Ca2+, because Ni2+ partially inhibited ANG II-induced PEt and obliterated agonist-mediated DAG formation. The consequence of Ca2+ modulation of PC metabolism was investigated by measuring PKC activity. Ni2+ had no effect on early (PI-associated) activation by ANG II at 90 s but obviated translocation from cytosol to the membrane at 10 min. The pathway responsible for PC-associated DAG was studied in PKC downregulated cells. Whereas downregulation prevented PLD-mediated PEt elevation, ANG II-stimulated DAG formation in myristate-labeled cells was unaltered, indicating PC-PLC activation. In summary, ANG II stimulates PC-PLD and PC-PLC in MC. PC-PLD is tightly regulated by PKC, whereas PC-PLC is stringently controlled by extracellular Ca2+. ANG II mediated PC breakdown principally via PC-PLC provides a mechanism for maintaining elevated DAG levels and PKC activation.
Barnett
R L
RL
Department of Medicine, School of Medicine, State University of New York at Stony Brook 11794.
Ruffini
L
L
Ramsammy
L
L
Pasmantier
R
R
Friedlaender
M M
MM
Nord
E P
EP
D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004075:Diglycerides / Q000096:biosynthesis; D004789:Enzyme Activation; D005110:Extracellular Space / Q000378:metabolism; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020404:Glycerophospholipids; D006868:Hydrolysis; D010712:Phosphatidic Acids / Q000096:biosynthesis; D010713:Phosphatidylcholines / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*
C011439:1,2-diacylglycerol; D004075:Diglycerides; D020404:Glycerophospholipids; D010712:Phosphatidic Acids; D010713:Phosphatidylcholines; C051521:phosphatidylethanol; D000804:Angiotensin II; D011493:Protein Kinase C; D002118:Calcium