Document 0161
 DOCN  M9650161
 TI    Cultured AIDS-related Kaposi's sarcoma (AIDS-KS) cells demonstrate
       impaired bioenergetic adaptation to oxidant challenge: implication for
       oxidant stress in AIDS-KS pathogenesis.
 DT    9605
 AU    Mallery SR; Bailer RT; Hohl CM; Ng-Bautista CL; Ness GM; Livingston BE;
       Hout BL; Stephens RE; Brierley GP; Department of Dentistry, College of
       Dentistry, Ohio State; University, Columbus 43210-1241, USA.
 SO    J Cell Biochem. 1995 Nov;59(3):317-28. Unique Identifier : AIDSLINE
       MED/96155663
 AB    Despite its recognition as the most prevalent HIV associated cancer,
       speculation still abounds regarding the pathogenesis of AIDS-related
       Kaposi's sarcoma (AIDS-KS). However, it has been established that both
       cytokines, e.g. IL-6, and HIV-associated products, e.g., Tat, are
       integral in AIDS-KS cellular proliferation. Further, both experimental
       and clinical evidence is accumulating to link reactive oxygen
       intermediates (ROI) with both cytokine induction (primarily via nuclear
       factor-kappa B[NF-kappa B] dependent routes) as well as the subsequent
       cytokine, tumor necrosis factor alpha (TNF alpha) stimulation of HIV
       replication. Features of AIDS-KS patients, such as retention of
       phagocytes, presence of sustained immunostimulation, and a frequent
       history of KS lesions arising at traumatized sites, make oxidant stress
       a viable clinical factor in AIDS-KS development. Time course nucleotide
       profile analyses show that AIDS-KS cells have an inherent, statistically
       significant, biochemical deficit, even prior to oxidant stress, due to
       1) a more glycolytic bioenergetic profile, resulting in lower levels of
       high energy phosphates (impairing capacity for glutathione [GSH]
       synthesis and DNA repair); 2) lower levels of NADPH (compromising the
       activities of GSSG reductase and peroxidase function of catalase); and
       3) reduced levels of GSH (impeding both GSH peroxidase and
       GSH-S-transferases). Following exposure to physiologically relevant
       levels of H2O2, only the human microvascular endothelial cells (a
       putative AIDS-KS progenitor cell) responded with bioenergetic
       adaptations that reflected co-ordination of energy generating and
       cytoprotective pathways, e.g., retention of the cellular energy charge,
       increased NAD+, and an accentuation of the ATP, NADPH, and total adenine
       nucleotide differences relative to AIDS-KS cells. Also, some of the
       AIDS-KS strains retained intracellular GSSG subsequent to oxidant
       challenge, inviting the formation of deleterious protein mixed
       disulfides. While the results of our study address some AIDS-KS issues,
       they also raise an etiological question, i.e., Does the inability to
       tolerate oxidant stress arise in conjunction with AIDS-KS neoplastic
       development, or is it pre-existing in the population at risk?
       Regardless, use of antioxidant therapy (low risk/ potentially high
       benefit) in both the at risk population as well as in those individuals
       with active disease may prove a useful preventative and/or treatment
       modality.
 DE    Acquired Immunodeficiency Syndrome/*COMPLICATIONS  Adenosine
       Triphosphate/METABOLISM  Cell Division  Cells, Cultured  Endothelium,
       Vascular/METABOLISM  *Energy Metabolism  Glutathione/METABOLISM  Human
       Hydrogen Peroxide/PHARMACOLOGY  NAD/METABOLISM  Oxidation-Reduction
       *Oxidative Stress  Reactive Oxygen Species/METABOLISM  Sarcoma,
       Kaposi's/*ETIOLOGY/*METABOLISM/PATHOLOGY  Support, U.S. Gov't, P.H.S.
       Trypsin/PHARMACOLOGY  Tumor Cells, Cultured  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).