Oxidative protein damage and degradation in lymphocytes from patients infected with human immunodeficiency virus.
It has been proposed that oxidative stress is the common mediator of apoptotic cell death in AIDS. However, mechanistic relationships between oxidative damage and cell death are far from clear. It is reported here that the mitogenic activation of T lymphocytes from human immunodeficiency virus-positive subjects involves perturbation of redox balance, as indicated by the increase in hydroethydine intracellular oxidation and manganese superoxide dismutase adaptive induction. Principal molecular targets of oxidative injury are cellular proteins whose content in carbonyl groups increases together with a dramatic increase in degradation of newly synthesized proteins catalyzed by the ATP- and ubiquitin-dependent proteolytic system. The major consequence of this metabolic anomaly is the decrease in protein cell mass leading to cells that are smaller than normal at lethal mitosis.
Piedimonte
G
G
Istituto di Patologia Generale e Anatomia Patologica e Dipartimento di Igiene e Medicina Preventiva, Università di Messina, Italy.
Guetard
D
D
Magnani
M
M
Corsi
D
D
Picerno
I
I
Spataro
P
P
Kramer
L
L
Montroni
M
M
Silvestri
G
G
Torres Roca
J F
JF
Montagnier
L
L
D000328:Adult; D017252:CD3 Complex / Q000096:biosynthesis; D004247:DNA / Q000096:biosynthesis; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D007930:Leucine / Q000378:metabolism; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism*; D008875:Middle Aged; D018384:Oxidative Stress; D011392:Proline / Q000493:pharmacokinetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D013482:Superoxide Dismutase / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism
D017252:CD3 Complex; D007376:Interleukin-2; D017382:Reactive Oxygen Species; D015375:Receptors, Interleukin-2; D013481:Superoxides; D004247:DNA; D011392:Proline; D013482:Superoxide Dismutase; D007930:Leucine