       Document 3254
 DOCN  M94A3254
 TI    Increased degradation of newly synthetized proteins in T-lymphocytes
       from HIV+ asymptomatic individuals.
 DT    9412
 AU    Piedimonte G; Silvotti L; Montroni M; Silvestri G; Guetard D; Montagnier
       L; University of Parme, Italy.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(1):118 (abstract no. PA0092). Unique
       Identifier : AIDSLINE ICA10/94369321
 AB    OBJECTIVE: Among early functional T-cell defects occuring after HIV
       infection, the reduction of IL-2 production and the reduced expression
       of surface molecules strongly suggest abnormalities at some stage of the
       cellular protein synthetic process. The aim of this work was to define
       the mechanism(s) involved in these alterations. METHODS: Experimental
       design adopted included: (i) measures of initial rates of protein
       synthesis and half life of newly synthetized proteins; (ii) evaluation
       of intracellular location and level of activity of enzymes specifically
       involved in proteolysis and protein-break down; (iii) analysis of
       structural modifications, especially oxidative denaturation of cellular
       proteins. Experiments have been carried out in T-lymphocytes from normal
       (48 individuals) and HIV+ asymptomatic (59 individuals) men in different
       phases of cell cycle, upon mitogenic stimulation. RESULTS: 1) The half
       life of newly synthetized lymphocyte proteins strongly decreases in HIV+
       asymptomatic individuals. Mean values are of 16 hr versus 59 hr
       recovered in normal individuals; 2) Patterns of subcellular distribution
       and activity of proteolytic enzymes are almost superimposable in normal
       and HIV+ T-cells: 3) Levels of activity of superoxide dismutase
       significatively decrease and superoxide anions production increase in
       activated HIV+ T-cells. CONCLUSIONS: Protein degradation is correlated
       with oxidative stress. In our system, mitogenic stimulation induces an
       increase of protein degradation parallel to the increases production of
       O2 anions. The lack of SOD induction and the unchanged distribution and
       activity of proteolytic enzymes suggest that accelerated protein
       degradation in HIV+ T-cells is the result of oxidative modifications of
       cell proteins rather than the consequence of protease activation.
 DE    Half-Life  Human  HIV Seropositivity/IMMUNOLOGY/*METABOLISM  In Vitro
       Interleukin-2/BIOSYNTHESIS  Lymphocyte Transformation  Male
       Oxidation-Reduction  Protein Denaturation
       Proteins/BIOSYNTHESIS/*METABOLISM  Subcellular Fractions/METABOLISM
       Superoxide Dismutase/METABOLISM  Superoxides/METABOLISM
       T-Lymphocytes/IMMUNOLOGY/*METABOLISM  MEETING ABSTRACT

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

