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)

Recent evidence has linked bacterial vaginosis with acquisition of sexually transmitted diseases, including HIV infection. Prospective data show that women with bacterial vaginosis are at a significantly higher risk for HIV infection than those without bacterial vaginosis. The hallmark of bacterial vaginosis is the shift in the microbiology of the vaginal flora away from a lactobacilli-predominant milieu. In particular, lactobacilli that produce hydrogen peroxide are notably absent. Hydrogen peroxide-producing lactobacilli have been shown in vitro to be virucidal to HIV. Thus, the lack of these apparently protective bacteria, along with other local changes resulting from the shift in microflora, is thought to represent a biological risk factor for HIV acquisition.
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PMID:Role of Vaginal Flora As a Barrier to HIV Acquisition. 1128 57

GP120 (the protein component of the HIV viral coat) is neurotoxic and may contribute to the cell loss associated with AIDS-related dementia. Previously, it has been shown in rat cortical mixed cultures that gp120 increased the accumulation of hydrogen peroxide and superoxide, two reactive oxygen species (ROS). We now demonstrate that gp120 increased activity of the key antioxidant glutathione peroxidase (GSPx), presumably as a defensive mechanism against the increased ROS load. Both estrogen and glucocorticoids (GCs), the adrenal steroid released during stress, blunted this gp120 effect on GSPx activity. The similar effects of estrogen and of GCs are superficially surprising, given prior demonstrations that GCs exacerbated and estrogens protected against gp120 neurotoxicity. We find that these similar effects of estrogen and GCs on GSPx regulation arose, in fact, from very different routes, which are commensurate with these prior reports. Specifically, estrogen has demonstrated antioxidant properties that may prevent the ROS increase (therefore acting as a neuroprotective agent) and rendered unnecessary the compensatory GSPx increased activity. To verify this we have added H2O2 to estrogen + gp120-treated cells, and GSPx activity was increased. However, with addition of H2O2 to GCs + gp120-treated cells there was no increase in activity. GCs appeared to decrease enzyme production and or activity and therefore under insult conditions ROS levels rose in the cell resulting in increased neurotoxicity. Overexpression of GSPx enzyme via herpes vector system reversed the GCs-induced loss of enzyme and eliminated the GCs exacerbation of gp120 neurotoxicity.
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PMID:Effect of GP120 on glutathione peroxidase activity in cortical cultures and the interaction with steroid hormones. 1206 74

Mitogenic cell proliferation requires a rapid and transient H2O2 generation, which is blocked by catalase or PKA activators. Previously, we observed that anemic HIV(+) individuals expressed acidic pIs of catalase in RBC with significantly high activities [Mol Cell Biochem 165: 77-81, 1996]. These findings led us to hypothesize that cell signaling molecules regulate catalase to control cell mitogenesis. To test the hypothesis, we determined (i) whether RBC counts correlate with their catalase activities, (ii) whether protein kinases and phosphatases alter catalase activity in vitro, and (iii) whether protein kinase activators increase catalase activity to suppress proliferation of cultured cells. The results indicated that RBC counts inversely correlated with RBC catalase activities in both HIV(+) (r: -0.6769, r2: 0.4582, n: 69 male, p < 0.0001) and HIV(-) (r: -0.3827, r2: 0.1464, n: 177 male, p < 0.0001) populations. Catalytic PKA, PKC and Casein Kinase II, but none of PKG, Ca2+/calmodulin kinase II and p34cdc/cyclinB, rapidly elevated catalase activity in vitro by up to 2-fold. Whereas a major CAT subunit (60 kDa) showed immunoreactive phosphoserine and phosphothreonine, the kinases- and gamma-32P-ATP-dependent phosphorylation occurred with a minor component (110 kDa). Among PKC isozymes examined, PKCzeta was the most effective modulator followed by PKCgamma, and protein phosphatase 1gamma and 2A decreased the catalase activity. PKA and PKCzeta activators of forskolin and okadaic acid increased catalase activity and 110 kDa expression in NIH3T3 cells up to 2.4-fold and suppressed the cell growth, showing an inverse correlation of the indices (r: -0.9286, r2: 0.8622, n: 18, p < 0.0001). Taken together, these results suggest for the first time that catalase is under the regulation of cell signaling molecules and capable of modulating mitogenic cell proliferation.
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PMID:Regulation of catalase enzyme activity by cell signaling molecules. 1248 79

A novel L-amino acid oxidase, named TSV-LAO, has been purified and cloned from the snake Trimeresurus stejnegeri. Fifty percentage cytotoxic concentrations (CC50) of TSV-LAO on C8166 cells were 24 and 390 nM in the absence or presence of catalase (400 nM), respectively. However, at concentrations that showed little effect on cell viability, TSV-LAO displayed dose dependent inhibition on HIV-1 infection and replication. The antiviral selectivity indexes (CC50/EC50) were 16 and 6, respectively, corresponding to the measurements of syncytium formation and HIV-1 p24 antigen expression. Interestingly, the presence of catalase resulted in an increase of its antiviral selectivity to 52 and 38. Under the same conditions, no anti-HIV-1 activity was observed by exogenous addition of H2O2. The complete amino acid sequence of TSV-LAO, as deduced from its cDNA, exhibits a high degree of sequence identity with other snake venom LAOs.
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PMID:Molecular characterization of Trimeresurus stejnegeri venom L-amino acid oxidase with potential anti-HIV activity. 1296 32

Pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP), and peptide histidine-isoleucine (PHI) belong to a structurally related family of polypeptides present in many regions of the central and peripheral nervous system. The neuroprotective potential of PACAP, VIP, and PHI has become a matter of intensive investigations in many animal models. In vitro studies revealed that PACAP protects neurons against apoptosis occurring naturally during CNS development and apoptosis induced by a series of neurotoxins, such as ethanol, hydrogen peroxide (H2O2), prion protein, beta-amyloid, HIV envelope glycoprotein (gp120), potassium ion deficit, and high glutamate concentrations. Similarly, in vivo investigations conducted in models of ischemia and Parkinson's disease confirmed the neuroprotective properties of PACAP. It was revealed that the anti-apoptotic action of PACAP can be directly associated with the activation of signal transduction pathways preventing apoptosis in neurons or involve glial cells capable of releasing other neuroprotective factors affecting neurons. In contrast to PACAP, the neuroprotective action of VIP depends mainly on stimulation of astrocytes to produce and secrete factors of extremely high neuroprotective potential, including activity-dependent neurotrophic factor (ADNF) and activity-dependent neuroprotective protein (ADNP). It was shown that ADNF and ADNP, as well as their shortened derivatives ADNF-9 and NAP, prevent neurons from electrical blockade, excitotoxicity, apoE deficiency, glucose deficit, ischemia, toxic action of ethanol, beta-amyloid, and gp120. The neuroprotective potential of PHI has not been as thoroughly investigated yet, but recent data have confirmed that this peptide can also function as a neuroprotectant. It is thought that PACAP, VIP, and possibly PHI may serve as a goal of modern therapeutic strategies in various neurodegenerative disorders.
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PMID:[Neuroprotective role of PACAP, VIP, and PHI in the central nervous system]. 1557 49

Patients with early HIV-1 infection develop an autoimmune thrombocytopenia in which antibody is directed against an immunodominant epitope of the beta3 (glycoprotein IIIa [GPIIIa]) integrin, GPIIIa49-66. This antibody induces thrombocytopenia by a novel complement-independent mechanism in which platelets are fragmented by antibody-induced generation of H2O2 derived from the interaction of platelet nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and 12-lipoxygenase. To examine whether sharing of epitope between host and parasite may be responsible for this immunodominant epitope, we screened for antibody-reactive peptides capable of inhibiting platelet lysis and oxidation in vitro, using a filamentous phage display 7-mer peptide library. Fourteen of these phage-peptide clones were identified. Five shared close sequence similarity with GPIIIa49-66, as expected. Ten were molecular mimics with close sequence similarity to HIV-1 proteins nef, gag, env, and pol. Seven were synthesized as 10-mers from their known HIV-1 sequence and found to inhibit anti-GPIIIa49-66-induced platelet oxidation/fragmentation in vitro. Three rabbit antibodies raised against these peptides induced platelet oxidation/fragmentation in vitro and thrombocytopenia in vivo when passively transferred into mice. One of the peptides shared a known epitope region with HIV-1 protein nef and was derived from a variant region of the protein. These data provide strong support for molecular mimicry in HIV-1-immunologic thrombocytopenia within polymorphic regions of HIV-1 proteins. A known epitope of nef is particularly incriminated.
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PMID:Role of molecular mimicry to HIV-1 peptides in HIV-1-related immunologic thrombocytopenia. 1577 14

It has been suggested that vaginal lactobacilli may influence heterosexual transmission of HIV infection. The aim of this study was to compare the vaginal flora on Gram's stained and isolation rate, quantity and H2O2 production of lactobacilli between HIV positive and HIV negative women. Although, the prevalence of abnormal vaginal flora was increased in HIV infected women, there was no significant difference in isolation rate of vaginal lactobacilli between the two groups (71.87 vs. 83.33%; P>0.05). However, the results of this study showed significantly reduced quantity of lactobacilli in HIV infected women (P<0.01). In particular, the prevalence of H2O2-producing lactobacilli was lower in HIV positive as compared to HIV negative women (80 vs. 56.52%), with borderline significance (P=0.057). Taken together, our findings showed altered vaginal microflora with reduced quantity and hydrogen-peroxide production of vaginal lactobacilli in HIV positive women, but further studies are needed to assess its actual significance and potential benefit from the use of probiotic therapy.
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PMID:Reduced quantity and hydrogen-peroxide production of vaginal lactobacilli in HIV positive women. 1627 44

L-Amino acid oxidase is a dimeric glycosylated flavoenzyme, a major constituent of the venom-from the snake Calloselasma rhodostoma. The enzyme exhibits apoptosis inducing effects as well as antibacterial and anti-HIV activities. The structure of l-amino acid oxidase with its substrate (L-phenylalanine) has been refined to a resolution of 1.8 A. The complex structure reveals the substrate bound to the reduced flavin (FADred). Alternative conformations for the key residues His223 and Arg322 are evident, suggesting a dynamic active site. Furthermore, conformational changes are apparent for the isoalloxazine ring; the three-ring system exhibits more bending around the N5-N10 axis compared to the oxidized flavin. The implications of the observed dynamics on the mechanism of catalysis are discussed. Inspection of buried surfaces in the enzyme reveals a Y-shaped channel system extending from the external surface of the protein to the active site. One portion of this channel may serve as the entry path for O2 during the oxidative half-reaction. The second region, separated from the proposed O2 channel by the N terminus (residues 8-16) of the protein, may play a role in H2O2 release. Interestingly, the latter portion of the channel would direct the H2O2 product to the exterior surface of the protein, near the glycan moiety, thought to anchor the enzyme to the host cell. This channel location may explain the ability of the enzyme to localize H2O2 to the targeted cell and thus induce the apoptotic effect.
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PMID:Crystal structure of LAAO from Calloselasma rhodostoma with an L-phenylalanine substrate: insights into structure and mechanism. 1704 20

Implementation of molecular tests for the assessment of pediatric HIV-1 infection in resource-limited countries is difficult because of technical complexity and costs. Alternatives like the ultrasensitive HIV-1 p24 antigen enzyme-linked immunosorbent assay have therefore been proposed. We have now adapted this test to dried blood spot (DBS) plasma p24 antigen (p24). High background activity was recognized as originating from endogenous peroxidase and eliminated by H2O2 quenching. The assay was evaluated with 72 pediatric specimens from Tanzania and with 210 pediatric or adult specimens from Switzerland. A real-time polymerase chain reaction assay for DBS DNA and/or plasma RNA identified HIV-1 infection in 38 Tanzanian children. HIV-1 subtypes included 18 C, 9 A1, 8 D, 1 AC, 1 J-like, and 1 unidentified. The detection rates for the different assays were as follows: DBS-p24, 32 (84%) of 38 samples; DBS DNA, 30 (79%) of 38 samples; plasma-p24, 23 (85%) of 27 samples; and plasma RNA, 30 (100%) of 30 samples. False-negative DBS-p24 was associated with subtype D (P < 0.01). DBS-p24 detection for non-D subtypes was 93% (95% confidence interval: 81% to 99%), and for subtype C, it was 94% (95% confidence interval: 76% to 99%). Specificity among 193 HIV-negative DBS samples was 100%. Correlation of DBS-p24 and plasma-p24 concentrations was excellent (R = 0.83, P < 0.0001). DBS-p24 is thus a promising alternative to molecular tests for HIV-1 in subtype C regions. It should now be evaluated in large studies of children for accurate assessment of diagnostic sensitivity.
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PMID:Adaptation of the ultrasensitive HIV-1 p24 antigen assay to dried blood spot testing. 1714 73

Human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) exerts multiple effects on viral and host cellular activities during infection, including induction of the cell cycle G2 arrest, and cell death in both human cells and the fission yeast Schizosaccharomyces pombe. We show that treament of exponential-phase wild-type Vpr-expressing S. pombe cells with a low, subinhibitory concentration (0.15 mmol/L) of hydrogen peroxide and 0.1 mmol/L thiamine significantly increased both cell proliferation and survival rates and decreased the number of elongated G2-arrested cells. Short-term, H2O2-induced adaptive stress increased the survival of the cells while acute stress conditions interrupted the Vpr-mediated death of the cells; however, no changes in cell length or cell phase were detected. The results suggest the importance of the oxidative status of the cells in Vpr-mediated processes. Our findings contribute to the development of a new approach via which to investigate the contribution of Vpr to HIV pathogenesis and to reduce the Vpr-mediated effects in HIV-infected patients.
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PMID:The dose-dependent H2O2 stress response promotes increased survival for Schizosaccharomyces pombe cells expressing HIV-1 Vpr. 1717 60


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