The effect of oxidant stress on human lymphocyte cytotoxicity

Grever,; Thompson, VN; Sp, Balcerzak; Sagone, AL Jr

doi:10.1182/blood.v56.2.284.284

Cited by 26 publications

(1 citation statement)

References 18 publications

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“…In addition, HIV-1-infected cells undergo an endogenous oxidative stress related to the inhibitory effect of the viral protein Tat on the activity of the manganese superoxide dismutase (12,50), leading to an increase in endogenous reactive oxygen intermediates. In vivo studies with animal models showed that oxidative stress induces an immunodeficiency with T-lymphocyte depletion (14)(15)(16)26). This conclusion fits with the observation that the high rate of apoptosis of CD4 ϩ T cells from HIV-infected individuals can be decreased ex vivo by the addition of antioxidant compounds such as N-acetylcysteine (NAC) (36).…”

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confidence: 56%

Human Immunodeficiency Virus Induces a Dual Regulation of Bcl-2, Resulting in Persistent Infection of CD4⁺T- or Monocytic Cell Lines

Aillet

Masutani

Elbim

et al. 1998

J Virol

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This work aims at characterizing the interplay between human immunodeficiency virus type 1 (HIV-1) and the antiapoptotic cellular protein Bcl-2 responsible for a persistent infection in lymphoblastoid T (J.Jhan) or monocytic (U937) cells. We report that the kinetics of Bcl-2 protein level during the establishment of a chronic infection is biphasic, characterized by a transient decrease followed by restoration to the initial level. The extent and duration of this transient decrease were inversely correlated with the basal level of Bcl-2 as shown by kinetics of Bcl-2 levels in J.Jhan or U937 clones exhibiting different levels of Bcl-2. Using these clones, we also showed that Bcl-2 downregulates HIV-1 replication. Therefore, the cells overexpressing Bcl-2 are characterized by a low viral burden which, in turn, has little effect on the level of this protein. The observed bipasic kinetics is the result of a dual regulation of Bcl-2 induced by HIV-1 infection itself: an upregulation at the transcriptional level of the bcl-2 gene concomitant with a downregulation at the protein level. Convergent data suggest that this downregulation is caused by the oxidative stress induced by the infection itself as shown by the associated modulations of glutathione and thioredoxin levels and by the prevention of these dysregulations byN-acetylcysteine. Altogether, these data indicate that infection first results in a decrease of Bcl-2, permitting an initial boost of replication. Then, as the synthesis at the transcriptional level proceeds, the replication is negatively controlled by Bcl-2 to reach a balance characterized by low virus production and a level of Bcl-2 compatible with cell survival. We suggest that the basal level of Bcl-2, together with infection-inducible transcription factors able to activate bcl-2 gene transcription, is a critical cellular determinant in the tendency toward an acute or a persistent infection.

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confidence: 56%

Human Immunodeficiency Virus Induces a Dual Regulation of Bcl-2, Resulting in Persistent Infection of CD4⁺T- or Monocytic Cell Lines

Aillet

Masutani

Elbim

et al. 1998

J Virol

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Inhibition of Early Events in the Human T-Lymphocyte Response to Mitogens and Alloantigens by Hydrogen Peroxide

Freed¹

1987

Arch Surg

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Effect of hyperoxia on the carbohydrate metabolism of human lymphocytes

Sagone

1985

American J Hematol

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Lymphocytes incubated under high oxygen tensions have impaired lymphoblastic transformation to nonspecific mitogens. Since carbohydrate metabolism may be essential for an optimal proliferation of these cells following an antigenic stimulus, we have characterized the effect of hyperoxia on the glucose metabolism of human lymphocytes in vitro. The mean rates of glucose utilization, Krebs cycle activity, and hexose monophosphate shunt activity were determined for unstimulated and phytohemagglutinin (PHA)-stimulated cultures incubated for 3 days. In unstimulated cultures, hyperoxia stimulated glucose utilization and markedly impaired Krebs cycle activity but did not alter HMPS activity. These observations suggest that hyperoxia impairs the mitochondrial activity of lymphocytes and that increased glycolysis compensates for the loss of cellular energy normally produced by this organelle. Under high oxygen tension PHA-stimulated cultures failed to show the burst in HMPS activity and increased Krebs cycle activity characteristic of cultures incubated under physiological oxygen tensions and consumed less glucose. Our results indicate that hyperoxia alters the glucose metabolism of lymphocytes. This metabolic alteration may be related to the impaired function of the cells under hyperoxic conditions.

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The effect of oxidant stress on human lymphocyte cytotoxicity

Cited by 26 publications

References 18 publications

Human Immunodeficiency Virus Induces a Dual Regulation of Bcl-2, Resulting in Persistent Infection of CD4⁺T- or Monocytic Cell Lines

Human Immunodeficiency Virus Induces a Dual Regulation of Bcl-2, Resulting in Persistent Infection of CD4⁺T- or Monocytic Cell Lines

Inhibition of Early Events in the Human T-Lymphocyte Response to Mitogens and Alloantigens by Hydrogen Peroxide

Effect of hyperoxia on the carbohydrate metabolism of human lymphocytes

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The effect of oxidant stress on human lymphocyte cytotoxicity

Cited by 26 publications

References 18 publications

Human Immunodeficiency Virus Induces a Dual Regulation of Bcl-2, Resulting in Persistent Infection of CD4+T- or Monocytic Cell Lines

Human Immunodeficiency Virus Induces a Dual Regulation of Bcl-2, Resulting in Persistent Infection of CD4+T- or Monocytic Cell Lines

Inhibition of Early Events in the Human T-Lymphocyte Response to Mitogens and Alloantigens by Hydrogen Peroxide

Effect of hyperoxia on the carbohydrate metabolism of human lymphocytes

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Product

Resources

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Human Immunodeficiency Virus Induces a Dual Regulation of Bcl-2, Resulting in Persistent Infection of CD4⁺T- or Monocytic Cell Lines

Human Immunodeficiency Virus Induces a Dual Regulation of Bcl-2, Resulting in Persistent Infection of CD4⁺T- or Monocytic Cell Lines