Document Detail


The inhibition of apoptosis in EL4 lymphoma cells overexpressing growth hormone.
MedLine Citation:
PMID:  15067206     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The antiapoptotic action of exogenous growth hormone (GH) has been reported for several lymphoid cell lines; however, the potential role of endogenous GH in apoptosis has not been thoroughly investigated. This study was designed to investigate the effects of endogenous GH on apoptosis induced by methyl methanesulfonate (MMS) in a T cell lymphoma overexpressing GH (GHo). The results of these experiments have shown that in EL4 lymphoma cells, overexpression of GH sustained viability after exposure to MMS compared to control cells. The extent of DNA fragmentation measured by ladder formation on agarose gels was reduced in GHo cells following treatment with MMS, when compared to control cells. Adding exogenous GH to control cells and treatment of GHo cells with antibodies to GH had no effect on MMS-induced DNA ladder formation. In further studies, DNA microarray analysis suggested a marked decrease in the constitutive expression of bax, BAD, and caspases 3, 8, and 9 in GHo cells compared to controls. In addition, after treatment with MMS, the activities of caspases 2, 3, 6, 8, and 9 were all lower than control in GHo cells. Western blot analysis detected an increase in Bcl-2 while the levels of nuclear factor kappa B (NFkappaB) remained unchanged in GHo cells. Treatment of EL4 cells with antisense deoxyoligonucleotides to GH and specific inhibitors of NFkappaB (SN-50) increased DNA fragmentation. GHo cells show increased levels of phosphorylated Akt and GSK-3, suggesting inactivation of this proapoptotic protein. The results, taken together with our previous data which showed increased nitric oxide formation in GHo cells, suggest a possible mechanism for the antiapoptotic effects of endogenous GH through the production of nitric oxide and support the idea that endogenous GH may play an important role in the survival of lymphocytes exposed to stressful stimuli.
Authors:
Robyn E Arnold; Douglas A Weigent
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Neuroimmunomodulation     Volume:  11     ISSN:  1021-7401     ISO Abbreviation:  Neuroimmunomodulation     Publication Date:  2004  
Date Detail:
Created Date:  2004-04-06     Completed Date:  2004-07-21     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9422763     Medline TA:  Neuroimmunomodulation     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  149-59     Citation Subset:  IM    
Copyright Information:
Copyright 2004 S. Karger AG, Basel
Affiliation:
Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, Ala. 35294-0005, USA.
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MeSH Terms
Descriptor/Qualifier:
Adjuvants, Immunologic / metabolism*
Animals
Antibodies / pharmacology
Apoptosis / drug effects,  genetics*
Carrier Proteins / genetics
Caspases / genetics
Cell Line, Tumor
Cell Survival / genetics
DNA Fragmentation / drug effects,  genetics
Glycogen Synthase Kinase 3 / metabolism
Growth Hormone / antagonists & inhibitors,  genetics,  metabolism*
Lymphoma / immunology,  metabolism*
Methyl Methanesulfonate
Mice
NF-kappa B / genetics
Nitric Oxide / metabolism
Protein-Serine-Threonine Kinases / metabolism
Proto-Oncogene Proteins / genetics,  metabolism
Proto-Oncogene Proteins c-akt
Proto-Oncogene Proteins c-bcl-2 / genetics
RNA, Messenger / drug effects,  metabolism
Stress, Physiological / immunology*,  metabolism
T-Lymphocytes / immunology,  metabolism*
bcl-2-Associated X Protein
bcl-Associated Death Protein
Grant Support
ID/Acronym/Agency:
AI41651/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Adjuvants, Immunologic; 0/Antibodies; 0/Bad protein, mouse; 0/Bax protein, mouse; 0/Carrier Proteins; 0/NF-kappa B; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/RNA, Messenger; 0/bcl-2-Associated X Protein; 0/bcl-Associated Death Protein; 10102-43-9/Nitric Oxide; 66-27-3/Methyl Methanesulfonate; 9002-72-6/Growth Hormone; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.26/Glycogen Synthase Kinase 3; EC 3.4.22.-/Caspases

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