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Zhu et.al 98 Apoptosis JPharmacolExpTher.pdf

Zhu et.al 98 Apoptosis JPharmacolExpTher.pdf

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Published by: Matias Ceballos Guzman on Dec 09, 2010
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02/10/2013

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0022-3565/98/2862-1103$03.00/0
 
THEJOURNAL OFPHARMACOLOGY ANDEXPERIMENTALTHERAPEUTICSVol. 286, No. 2Copyright © 1998 by The American Society for Pharmacology and Experimental Therapeutics
 Printed in U.S.A.
JPET 286:1103–1109, 1998
9
-Tetrahydrocannabinol Induces Apoptosis inMacrophagesand Lymphocytes: Involvement of Bcl-2 and Caspase-1
1
WEIGANG ZHU, HERMAN FRIEDMAN and THOMAS W. KLEIN
Department of Medical Microbiology and Immunology, University of South Florida, College of Medicine, Tampa,Florida
Accepted for publication April 23, 1998 This paper is available online at http://www.jpet.org
ABSTRACT
Apoptosis is programed cell death characterized by certaincreased fragmentation under these conditions. Resident peri-cellular changes and regulated by various gene products in-toneal macrophages cultured with lipopolysaccharides showedcluding Bcl-2 and caspase-1. The marijuana cannabinoid,no obvious fragmentation unless they were also treated with9tetrahydrocannabinol (THC), has been reported to suppressTHC. Time course studies examining DNA fragmentation andin culture the proliferation of splenocytes and increase thecell membrane integrity (assessed by dye exclusion) showedrelease of IL-1 from macrophages; however, the mechanismsthat fragmentation preceded membrane damage indicating thatof these effects remain unclear. Because cannabinoids haveTHC induced apoptosis rather than cell necrosis. In addition,also been reported to induce apoptosis and because the re-THC treatment of splenocytes resulted in a decrease of Bcl-2lease of IL-1 and suppression of lymphoproliferation are relatedmRNA and protein as measured by Northern and Westernto apoptosis, we tested for the induction of apoptosis by THCblotting, respectively, and the drug induced apoptosis wasin murine immune cell cultures. Splenocytes cultured with Conblocked by the caspase inhibitor, Ac-Tyr-Val-Ala-L-asparticA for up to 24 hr showed evidence of DNA fragmentationacid aldehyde. These data suggest that THC treatment of cul-determined by gel electrophoresis, terminal deoxynucleotidetured immune cells induces apoptosis through the regulation of transferase-mediated dUTP-fluorescein nick end labeling andBcl-2 and caspase activity.

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