Catalytic activity-independent pathway is involved in phospholipase A(2)-induced apoptotic death of human leukemia U937 cells via Ca(2+)-mediated p38 MAPK activation and mitochondrial depolarization

Toxicology Letters
Wen-Hsin LiuLong-Sen Chang

Abstract

In view of the controversial role of catalytic activity on the cytotoxicity of phospholipase A(2) (PLA(2)), the present study is conducted to explore whether PLA(2) induces apoptotic process of human leukemia U937 cells through catalytic activity-independent pathway. Modification of His-48 (according to the sequence alignment with porcine pancreatic PLA(2)) with p-bromophenacyl bromide (BPB) caused over 99.9% drop in enzymatic activity Naja naja atra PLA(2). It was found that BPB-PLA(2)-induced apoptotic death of U937 cells was associated with mitochondrial depolarization, modulation of Bcl-2 family members, cytochrome c release and activation of caspases 9 and 3. Upon exposure to BPB-PLA(2), elevation of intracellular Ca(2+) levels and p38 MAPK activation were observed in U937 cells. Pretreatment with BAPTA-AM (Ca(2+) chelator) and nifedipine (L-type Ca(2+) channel blocker) abrogated Ca(2+) increase and p38 MAPK activation, and rescued viability of BPB-PLA(2)-treated U937 cells. BPB-PLA(2)-induced dissipation of mitochondrial membrane potential and down-regulation of Bcl-2 were suppressed by SB202190 (p38MAPK inhibitor). Although PLA(2) mutants in which His-48 and Asp-49 were substituted by Ala and Lys, respectively, did not d...Continue Reading

References

Dec 14, 1990·Science·D L ScottP B Sigler
Jul 15, 1998·Toxicon : Official Journal of the International Society on Toxinology·H ZhaoZ Lin
Oct 26, 2000·Nature·M O Hengartner
Mar 29, 2001·Progress in Lipid Research·E A Capper, L A Marshall
Dec 26, 2001·Molecular Pharmacology·Tatsurou YagamiYozo Hori
Mar 14, 2002·Journal of Neuroscience Research·Mark A DeCosterNicolas G Bazan
Jun 18, 2002·Journal of Neurochemistry·Tatsurou YagamiYozo Hori
Jul 12, 2002·Journal of Neuroscience Research·Elena B Rodriguez De TurcoNicolas G Bazan
Oct 29, 2002·FEBS Letters·Lucía FuentesMariano Sánchez Crespo
Jan 18, 2003·Biochimica Et Biophysica Acta·Makoto Mark Taketo, Masahiro Sonoshita
Feb 5, 2003·Experimental Cell Research·Sergey Ya ProskuryakovVladimir L Gabai
Dec 6, 2003·Journal of Lipid Research·Grace Y SunAgnes Simonyi
Mar 17, 2004·Toxicon : Official Journal of the International Society on Toxinology·Andreimar M Soares, José R Giglio
Mar 17, 2004·Toxicon : Official Journal of the International Society on Toxinology·Bruno LomonteLeonel Calderón
Sep 10, 2004·American Journal of Physiology. Cell Physiology·Paul S BrookesShey-Shing Sheu
Jan 5, 2005·Archives of Biochemistry and Biophysics·Paul Waring
May 3, 2005·FEBS Letters·Manabu AriokaKatsuhiko Kitamoto
Apr 28, 2006·The EMBO Journal·Paulina J DlugoszDavid W Andrews
May 6, 2006·Cell Death and Differentiation·C GarridoG Kroemer
May 9, 2006·Biochimica Et Biophysica Acta·Vladimir GogvadzeBoris Zhivotovsky
May 23, 2006·The Journal of Biological Chemistry·Giovanna De ChiaraFederico Cozzolino
Nov 17, 2007·Journal of Peptide Science : an Official Publication of the European Peptide Society·Pei-Hsiu KaoLong-Sen Chang
Nov 21, 2007·Toxicon : Official Journal of the International Society on Toxinology·Yi-Ling ChiouLong-Sen Chang

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