Document Detail

Effects of (15S)-hydroperoxyeicosatetraenoic acid and (15S)-hydroxyeicosatetraenoic acid on the acute- lymphoblastic-leukaemia cell line Jurkat: activation of the Fas-mediated death pathway.
MedLine Citation:
PMID:  18494609     Owner:  NLM     Status:  MEDLINE    
The antiproliferative effects of 15-LOX (15-lipoxygenase) metabolites of arachidonic acid {(15S)-HPETE [(15S)-hydroperoxyeicosatetraenoic acid] and (15S)-HETE [(15S)-hydroxyeicosatetraenoic acid]} and the mechanism(s) involved were studied in the human T-cell leukaemia cell line Jurkat. (15S)-HPETE, the hydroperoxy metabolite of 15-LOX, inhibited the growth of Jurkat cells 3 h after exposure and with an IC(50) value of 10 microM. The hydroxy metabolite of 15-LOX, (15S)-HETE, on the other hand, inhibited the growth of Jurkat cells after 6 h of exposure and with an IC(50) value of 40 microM. The cells exposed to 10 microM (15S)-HPETE for 3 h or to 40 microM (15S)-HETE for 6 h showed increased expression of Fas ligand and FADD (Fas-associated death domain), caspase 8 activation, Bid (BH3-interacting domain death agonist) cleavage, decrease in mitochondrial membrane potential, cytochrome c release, caspase 3 activation, PARP-1 [poly(ADP-ribose) polymerase-1] cleavage and DNA fragmentation, suggesting the involvement of both extrinsic and intrinsic death pathways. Further studies on ROS (reactive oxygen species) generation revealed the involvement of NADPH oxidase. In conclusion, the present study indicates that NADPH oxidase-induced ROS generation activates the Fas-mediated death pathway.
Kotha Anil Kumar; Kalle M Arunasree; Karnati R Roy; Nishanth P Reddy; Ankireddy Aparna; Gorla Venkateswara Reddy; Pallu Reddanna
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biotechnology and applied biochemistry     Volume:  52     ISSN:  1470-8744     ISO Abbreviation:  Biotechnol. Appl. Biochem.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-01-02     Completed Date:  2009-02-23     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8609465     Medline TA:  Biotechnol Appl Biochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  121-33     Citation Subset:  IM    
Department of Animal Sciences, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India.
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MeSH Terms
Antigens, CD95 / metabolism
Apoptosis / drug effects
Apoptosis Regulatory Proteins / metabolism
Arachidonate 15-Lipoxygenase / metabolism
Caspases / metabolism
Cell Cycle / drug effects
Cell Death / drug effects
Cell Proliferation / drug effects
Cytochromes c / metabolism
DNA Fragmentation / drug effects
Enzyme Activation / drug effects
Fas Ligand Protein / metabolism*
Flow Cytometry
Jurkat Cells
Leukotrienes / chemistry*,  pharmacology*
Lipid Peroxides / chemistry*,  pharmacology*
Membrane Potential, Mitochondrial / drug effects
NADPH Oxidase / metabolism
Poly(ADP-ribose) Polymerases / metabolism
Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology*
Proto-Oncogene Proteins c-akt / metabolism
Reactive Oxygen Species / metabolism
Signal Transduction / drug effects*
Reg. No./Substance:
0/Antigens, CD95; 0/Apoptosis Regulatory Proteins; 0/Fas Ligand Protein; 0/Leukotrienes; 0/Lipid Peroxides; 0/Reactive Oxygen Species; 67675-14-3/15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; 9007-43-6/Cytochromes c; EC 15-Lipoxygenase; EC Oxidase; EC Polymerases; EC Proteins c-akt; EC 3.4.22.-/Caspases

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