Secretory phospholipase A2 induces apoptosis through TNF-alpha and cytochrome c-mediated caspase cascade in murine macrophage RAW 264.7 cells.
Phospholipase A2 (PLA2) is an esterase that cleaves the sn-2 ester bond in glycerophospholipids, thereby releasing free fatty acids and lysophospholipids. In addition to the apoptotic activity of cytosolic PLA2 and Ca2+-independent PLA2, recent studies showed that secretory PLA2 (sPLA2) also play a role in apoptosis. However, the details of molecular mechanism have not been fully elucidated. Our data demonstrated that group IB PLA (IB PLA2)-exposed murine macrophage 264.7 cells showed characteristic features of apoptosis such as morphological changes, DNA laddering, staining positive for propidium iodide (PI) as well as Annexin V and activation of caspases and subsequent cleavage of poly (ADP-ribose) polymerase (PARP) in dose- and time-dependent manner. Moreover, IB PLA2 was found to elicit tumor necrosis factor (TNF)-alpha production and release of cytochrome c, suggesting that IB PLA2 exerts its apoptotic activity via the induction of TNF-alpha production and cytochrome c release, which results in triggering the activation of caspase cascade and PARP cleavage.
Aging-Associated Vascular Disease Research Center, Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, Daegu 705-717, South Korea.
ChuHee
C
Lee
Dae-Weon
DW
Park
Jingu
J
Lee
Tae-Il
TI
Lee
Young-Jo
YJ
Kim
Yun-Sik
YS
Lee
Suk-Hwan
SH
Baek
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3; D053179:Caspase 7; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D002460:Cell Line; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D054500:Group IB Phospholipases A2; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D010741:Phospholipases A / Q000494:pharmacology*; D054467:Phospholipases A2; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013552:Swine; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000276:immunology
D000906:Antibodies; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D010741:Phospholipases A; D054500:Group IB Phospholipases A2; D054467:Phospholipases A2; C516203:Pla2g1b protein, mouse; C505409:Casp3 protein, mouse; C505524:Casp7 protein, mouse; D053148:Caspase 3; D053179:Caspase 7; D020169:Caspases