Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antibodies reacting with the gag protein p17 of the human immunodeficiency virus type 1 (HIV-1) can occasionally be found in the serum of non-HIV-1-infected individuals. Conversely, anti-p17 antibodies can also react with human tissues from non-infected individuals. Here we report on the isolation from human liver of a molecule that is immunoreactive with anti-p17 antibodies. This molecule was purified to homogeneity and identified as superoxide dismutase-2 (manganese type SOD). Both human SOD-2 and HIV-1 p17 contain the LQPALK hexapeptide which may serve as a common antigenic determinant. This study indicates that human SOD-2 is a target for anti-p17 antibodies and suggests that HIV-1-negative individuals may possess SOD-2 auto-antibodies that cross-react with HIV-1 p17.
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PMID:Antibodies to the HIV-1 p17 protein cross-react with human superoxide dismutase-2. 902 42

TNF-alpha stimulates HIV-1 replication via activation of the transcription factor NF-kappa B. TNF-mediated activation of NF-kappa B is known to involve the intracellular formation of reactive oxygen intermediates (ROIs). We recently demonstrated that HIV-1 Tat protein potentiates TNF-induced NF-kappa B activation by downregulation of manganese-dependent superoxide dismutase (MnSOD), shifting the cellular redox state towards pro-oxidative conditions. This study shows that treatment of Jurkat cells with iron chelator deferoxamine (DFO) strongly decreases HIV-1 Tat-potentiated TNF-induced NF-kappa B activation but does not modify NF-kappa B activation by TNF-alpha. The ability of iron chelators to reduce Tat-potentiated TNF-induced NF-kappa B binding activity suggests that iron and intracellular hydroxyl radicals (OH.) are required for Tat effect. Moreover, we have shown that exogenously generated OH. markedly enhanced TNF-induced NF-kappa B activation in a dose-dependent manner while was not sufficient to trigger activation of NF-kappa B by itself. In addition, iron chelators had no effect either on MnSOD activity or on the decrease of this activity by Tat. Iron chelators had also no effect on the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG), but could elevate the GSH:GSSG ratio decreased by Tat protein. These observations suggest that the formation of intracellular OH. in the presence of iron ions play a major role in HIV-1 Tat enhancement of TNF-induced NF-kappa B activation and that iron chelation may protect Jurkat T cells, at least in part, against oxidative stress induced by Tat.
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PMID:Iron chelation decreases human immunodeficiency virus-1 Tat potentiated tumor necrosis factor-induced NF-kappa B activation in Jurkat cells. 911 Jan 46

The frequent neoplastic disorders present in HIV-infected patients and the implication of oxidative stress in AIDS-Kaposi's sarcoma pathogenesis prompted us to study whether the mechanisms implicated in genotoxic effects of clastogenic factors (CFs) (i.e., chromosome damaging materials released by cells under conditions of oxidant stress) can play a role in HIV-1 expression and whether exogenous superoxide dismutase can inhibit the clastogenic and HIV-inducing effects of CFs. CFs were found in the plasma of all HIV-1 infected patients (n = 21) of this study group, in asymptomatic (CDC II) as well as in symptomatic patients (CDC IV). In addition to their chromosome damaging effect, CFs are able to upregulate HIV-1 expression in U1 cells and in PBMCs activated with PHA and IL2 at all time points (p < .05). Their formation, therefore, is an early event in the disease. It occured despite antiviral medication in these patients. Superoxide dismutase inhibited the clastogenic and the viral inducing effects (p < .05). On the basis of our findings, association of SOD mimetics or superoxide scavengers with antiviral drugs may be a new therapeutic approach. This polytherapy, if started early enough after infection, may prolong the latency period and limit the emergence of drug-resistant viral strains.
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PMID:Clastogenic factors in plasma of HIV-1 infected patients activate HIV-1 replication in vitro: inhibition by superoxide dismutase. 921 3

3'-Azido-2',3'-dideoxythymidine (AZT, zidovudine) is the principal antiretroviral agent in the treatment of AIDS. Although beneficial, AZT remains restricted for human usage because of its severe toxic effects. We examined the AZT sensitivity in transgenic mice expressing HIV-1 one-exon-encoded 72 amino acid Tat (Tat72) and full-length 86 amino acid Tat (Tat86) proteins. Administration of AZT (1 mg/ml) in drinking water for 1 week resulted in a three- to fourfold decrease in hematopoietic progenitors from bone marrow in Tat mice compared to AZT-treated nontransgenic controls as determined by erythroid and granulocyte/macrophage colony-forming unit assays. In liver and thymus, two of the tissues examined, AZT treatment of Tat mice resulted in as much as 80-90% suppression of Mn-superoxide dismutase (Mn-SOD) activity. Other parameters associated with loss of Mn-SOD such as increase in carbonyl proteins and decrease of sulfhydryl content were also significantly enhanced by AZT in Tat mice. Our in vivo study suggests that AZT therapy is associated with oxidative damage affecting cellular functions in several tissues and that Tat is one of the contributory factors in AZT-induced toxicities. The findings of AZT-induced oxidative damage may help to improve the therapeutic index of AZT and other related drugs in AIDS patients.
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PMID:The human immunodeficiency virus type 1 Tat protein potentiates zidovudine-induced cellular toxicity in transgenic mice. 922 27

Reactive oxygen species (ROS) may play an important role in HIV-1 pathogenesis and HIV-1 gp120-induced neurotoxicity. Our studies determined the extent to which gp120 increased ROS production in human monocytic U937 cells and the effectiveness of various agents, including dipyridamole (DPR), in blocking these responses. The thiobarbituric acid-reactive substances (TBARS) assay was used as a measure of recombinant gp120 (HIV-1[3B])-induced oxidative damage to U937 cells. As a control, TBARS production was measured using a hypoxanthine/xanthine superoxide generating system. There was gp120-induced oxidative damage in U937 cells with a concentration that produces 50% of maximal effect (apparent EC50 value) of 11 pM. Polyclonal antiserum to gp120 significantly (p < 0.05) inhibited gp120-induced oxidative damage. gp120-induced oxidative damage was significantly inhibited 81% (p < 0.01) by catalase/superoxide dismutase, 53% (p < 0.05) by (+/-)-alpha-tocopherol, 78% (p < 0.01) by desferrioxamine, and 82% (p < 0.01) by ethylene diamine tetraacetic acid (EDTA). These results indicate that gp120 is capable of promoting iron-based oxygen free radical damage to U937 cells. DPR potently (p < 0.05) inhibited both hypoxanthine/xanthine- and gp120-induced oxidative damage with concentrations that produce 50% inhibition (apparent IC50 values) of 1.3 microM for hypoxanthine/xanthine and 1.0 microM for gp120. Therapeutic intervention against ROS production may prevent HIV-1 neurotoxicity.
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PMID:Antioxidants and dipyridamole inhibit HIV-1 gp120-induced free radical-based oxidative damage to human monocytoid cells. 940 67

Haemophilus ducreyi causes chancroid, a sexually transmitted genital ulcer disease implicated in increased heterosexual transmission of HIV. As part of an effort to identify H. ducreyi gene products involved in virulence and pathogenesis, we created random TnphoA insertion mutations in an H. ducreyi 35000 library cloned in Escherichia coli. Inserts encoding exported or secreted PhoA fusion proteins were characterized by DNA sequencing. One such clone encoded a Cu-Zn superoxide dismutase (SOD) enzyme. The Cu-Zn SOD was periplasmic in H. ducreyi and accounted for most of the detectable SOD activity in whole-cell lysates of H. ducreyi grown in vitro. To investigate the function of the Cu-Zn SOD, we created a Cu-Zn SOD-deficient H. ducreyi strain by inserting a cat cassette into the sodC gene. The wild-type and Cu-Zn SOD null mutant strains were equally resistant to excess cytoplasmic superoxide induced by paraquat, demonstrating that the Cu-Zn SOD did not function in the detoxification of cytoplasmic superoxide. However, the Cu-Zn SOD null strain was significantly more susceptible to killing by extracellular superoxide than the wild type. This result suggests that the H. ducreyi Cu-Zn SOD may play a role in bacterial defence against oxidative killing by host immune cells during infection.
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PMID:Periplasmic copper-zinc superoxide dismutase protects Haemophilus ducreyi from exogenous superoxide. 948 94

In HIV infected patients, the increase of the concentration of free radicals is related to: a depletion of protective system (glutathione peroxidase, superoxide dismutase, vitamin E, selenium ...), and an increased production of free radicals (superoxide anion, hydrogen peroxide, hydroxil radical) consecutive to the activation of lymphocytes and phagocyting cells, the chronic inflammation, the increased polyinsatured fatty acids concentration and lipoperoxidation, and direct or indirect effect of several pathologic agents including Mycoplasma sp. This free radical excess could impair cell membranes and generate apoptosis, the main cause of lymphocytes CD4+ depletion. After a brief review of the free radicals synthesis pathway, their potential deleterious effects and the protective systems, the role of free radicals in the pathogenesis of HIV infection are discussed in regard to data reported in the literature.
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PMID:[Free radicals and HIV infection]. 975 55

Haemophilus ducreyi is the etiologic agent of the sexually transmitted disease chancroid, an ulcerative condition implicated in increased HIV transmission. There is increasing evidence for the roles of oxidative stress proteins including superoxide dismutase enzymes in the survival and persistence of pathogenic organisms within the host. The sodA gene of Haemophilus ducreyi was isolated from a genomic plasmid library on the basis of its ability to rescue the hydrogen peroxide hypersensitivity of an Escherichia coli sodA sodB strain. The H. ducreyi SodA protein also complemented the aerobic growth defect of the E. coli sodA sodB strain in minimal medium. The deduced amino-acid sequence of the H. ducreyi sodA gene product is 74 and 70% identical to the Mn-SODs of Haemophilus influenzae and E. coli, respectively. However, unlike Mn-SODs, the H ducreyi SodA protein was inhibited by hydrogen peroxide in native gels stained for SOD activity.
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PMID:The sodA gene of Haemophilus ducreyi encodes a hydrogen peroxide-inhibitable superoxide dismutase. 951 68

Both clinical and experimental evidence indicates that AIDS-related Kaposi's sarcoma (AIDS-KS) has a multifactorial pathogenesis with factors such as HIV viral load, latent virus induction, and opportunistic infections contributing to disease progression. However, a consistent feature that unites these apparently diverse putative etiologic agents is sustained serum elevations of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha). While virtually every cell responds to TNF-alpha with gene activation, the extent of TNF-alpha-mediated cellular signaling is regulated by a delicate balance between signal activation and signal arresting events. Reactive oxygen intermediates (ROI), which are generated as a consequence of TNF-alpha membrane interaction, are part of this TNF-alpha-initiated cellular activation cascade. Previous studies in our laboratory have shown that AIDS-KS cells possess impaired oxygen intermediate scavenging capacities, thereby establishing conditions permissive for the intracellular retention of ROI. In this study, we used cellular capacity to upregulate the cytoprotective enzyme superoxide dismutase (SOD) to address the extent of cellular response to TNF-alpha. Concurrent with the SOD analyses, nucleotide profiles were obtained to assess cellular bioenergetic responses during TNF-alpha challenge. Proliferative growth levels of mitochondrial (Mn)SOD activities showed an activity spectrum ranging from lowest activity in AIDS-KS cells, to intermediate levels in matched, nonlesional cells from the AIDS-KS donors, to highest activities in HIV normal fibroblasts. In contrast, following TNF-alpha challenge, the AIDS-KS and KS donor nonlesional cells showed a 11.89- and 5.86-fold respective increase in MnSOD activity, while the normal fibroblasts demonstrated a 1.35-fold decrease. Subsequent thiol redox modulation studies showed that only the normal fibroblast cultures showed a potentiation of TNF-alpha-mediated MnSOD upregulation following GSH depletion. In addition, provision of the GSH precursor, N-acetylcysteine during TNF-alpha challenge only diminished MnSOD activity and mitochondrial compartmentalization in the AIDS-KS cells, a finding that likely reflects the lower levels of reduced thiols in this cellular population. Our data, which show that a perturbation in their cellular thiol redox status accentuates AIDS-KS cellular responsiveness to TNF-alpha, suggest a biochemical rationale for the recognized TNF-alpha AIDS-KS clinical correlation.
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PMID:Thiol redox modulation of tumor necrosis factor-alpha responsiveness in cultured AIDS-related Kaposi's sarcoma cells. 951 60

It has been previously demonstrated that HIV-1 infection induces a downregulation of MnSOD transcription in CD4+ lymphocytes. Using clinical isolates of macrophage-tropic HIV-1 strains we report here that conversely, purified normal human monocyte-derived macrophages (MDMs) overexpress the manganese superoxide dismutase (MnSOD) gene in response to infection and viral replication. This upregulation of MnSOD gene expression is concomitant with tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) production and treatment of HIV-1-infected MDMs with a specific transcriptional inhibitor of TNF-alpha synthesis counteracts the HIV-1-induced MnSOD gene activation. Moreover, TNF-alpha but not IL-6 addition mimicks the effects of HIV-1 infection on MnSOD gene regulation in normal MDM cultures. These observations strongly suggest that the MnSOD gene induction detected in HIV-1-infected MDMs is triggered by TNF-alpha produced in culture supernatants in parallel to HIV-1 particle release. In contrast to MnSOD, HIV-1 infection or replication in human MDMs has no effect on copper-zinc superoxide dismutase (Cu/ZnSOD) gene expression.
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PMID:HIV type 1 infection of human macrophages induces an upregulation of manganese superoxide dismutase gene that may protect cells from death. 954 2


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