| Implications for oxidative and nitrative stress in the pathogenesis of AIDS-related Kaposi's sarcoma. | |
| | |
MedLine Citation:
|
PMID: 14656937 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
AIDS-related Kaposi's sarcoma (AIDS-KS), which is the most prevalent AIDS related cancer, arises in a unique environment characterized by profound immunosuppression in conjunction with sustained immunostimulation. Persistent inflammation and the accompanying increased production of reactive species can promote carcinogenesis by numerous routes including sustained cell proliferation, initiation of nuclear and mitochondrial DNA mutations and induction of a proangiogenic environment. Furthermore, during conditions of continuous inflammation, protein nitration can result in irreversible inactivation of enzymes including the cytoprotective and reactive species degrading enzyme, mitochondrial superoxide dismutase (MnSOD). Because MnSOD serves as a putative tumor suppressor gene in addition to its reactive species inactivating capacities, the loss of MnSOD's cytoprotective functions could markedly facilitate malignant transformation. The purpose of this study was to investigate biochemical and molecular pathways by which reactive species facilitate AIDS-KS pathogenesis. Immunohistochemical studies of AIDS-KS tumors showed intense AIDS-KS lesional cell staining for MnSOD, inducible nitric oxide synthase (NOS 2) and the presence of a cellular 'fingerprint' of nitrative stress, 3-nitrotyrosine. Collectively, these results that imply reactive species stress occurs in situ. Similarly, cultured AIDS-KS cells derived from the AIDS-KS tumors contained both MnSOD protein and the 'high output' isoform, NOS 2. Co-localization studies established that the mitochondria are a primary site for 3-nitrotyrosine localization and immunoprecipitation/immunoblotting experiments confirmed that MnSOD tyrosine nitration occurs in AIDS-KS cells. Functional SOD assays showed that AIDS-KS cells possess significantly lower MnSOD activity relative to matched control cells; findings which correspond with ongoing MnSOD tyrosine nitration and subsequent inactivation within AIDS-KS cells. These results, which show in situ evidence of reactive species stress within AIDS-KS tumors and functional deficits attributable to nitrative stress in tumor-derived AIDS-KS lesional cells, imply that reactive species are intimately associated with AIDS-KS pathogenesis and provide insights for development of novel strategies for AIDS-KS clinical treatments. |
| | |
Authors:
|
Susan R Mallery; Ping Pei; David J Landwehr; Christopher M Clark; Jennifer E Bradburn; Gregory M Ness; Fredika M Robertson |
Related Documents
:
|
6147547 - Clinical findings and serological evidence of htlv-iii infection in homosexual contacts... 4064047 - Urinary excretion of modified nucleosides in patients with acquired immune deficiency s... 9720757 - Kaposi's sarcoma: a result of the interplay among inflammatory cytokines, angiogenic fa... 3261737 - Pneumocystis carinii antigenemia in acquired immunodeficiency syndrome. 8064027 - Hard-to-manage preschool boys: externalizing behavior, social competence, and family co... 1805667 - Parasitology collections in museum. |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. Date: 2003-12-04 |
Journal Detail:
|
Title: Carcinogenesis Volume: 25 ISSN: 0143-3334 ISO Abbreviation: Carcinogenesis Publication Date: 2004 Apr |
Date Detail:
|
Created Date: 2004-03-23 Completed Date: 2004-07-14 Revised Date: 2011-09-26 |
Medline Journal Info:
|
Nlm Unique ID: 8008055 Medline TA: Carcinogenesis Country: England |
Other Details:
|
Languages: eng Pagination: 597-603 Citation Subset: IM |
Affiliation:
|
Department of Oral Maxillofacial Surgery and Pathology, College of Dentistry, Ohio State University, Columbus, Ohio, USA. mallery.1@osu.edu |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Acquired Immunodeficiency Syndrome
/
complications* Biopsy Humans Isoenzymes / analysis Nitrates / physiology Nitric Oxide Synthase / analysis Oxidative Stress / physiology* Sarcoma, Kaposi / epidemiology, pathology*, physiopathology* Superoxide Dismutase / metabolism |
| Grant Support | |
ID/Acronym/Agency:
|
CA R01 95901/CA/NCI NIH HHS; CA U01 66351/CA/NCI NIH HHS; R01 CA095901-01A1/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Isoenzymes; 0/Nitrates; EC 1.14.13.39/Nitric Oxide Synthase; EC 1.15.1.1/Superoxide Dismutase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Ethical aspects of molecular epidemiology of cancer.
Next Document: Cellular protein kinase C isozyme regulation by exogenously delivered physiological disulfides--impl...