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M94A3254.TXT
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1994-10-25
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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).