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)

In addition to their conventional G-C/T target sequences, Sp1 family transcription factors (Sp-factors) can interact with a subset of the target sequences for NFkappaB. Due to the low level of bona fide NFkappaB activity in most resting cells, this interaction between Sp-factors and kappaB-sites could play important roles in cell function. Here we used mutagenesis of a canonical kappaB element from the immunoglobulin and HIV promoters to identify the GC-rich sequences at each end required for Sp-factor targeting. Through screening of multiple kappaB elements, a sequence element located in the second intron of superoxide dismutase-2 (SOD2) was identified as a good candidate for both NFkappaB and Sp-factor binding. In neurons, the prominent proteins interacting with this site were Sp3 and Sp4, whereas Sp1, Sp3, and NFkappaB were associated with this site in astroglia. The neuronal Sp-factors repressed transcriptional activity through this kappaB-site. In contrast, astroglial Sp-factors activated promoter activity through the same element. NFkappaB contributed to control of the SOD2 kappaB element only in astrocytes. These findings imply that cell-type specificity of transcription in the central nervous system, particularly with regard to kappaB elements, may include two unique aspects of neurons: 1) a recalcitrant NFkappaB and 2) the substitution of Sp4 for Sp1.
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PMID:Differential transcriptional control of the superoxide dismutase-2 kappaB element in neurons and astrocytes. 1702 25

Mononuclear phagocytes (bone marrow monocyte-derived macrophages, alveolar macrophages, perivascular macrophages, and microglia) are reservoirs and vehicles of dissemination for the human immunodeficiency virus type-1 (HIV-1). How virus alters mononuclear phagocyte immunoregulatory activities to complete its life cycle and influence disease is incompletely understood. In attempts to better understanding the influence of virus on macrophage functions, we used one-dimensional electrophoresis, and liquid chromatography tandem mass spectrometry to analyze the secretome of HIV-1-infected human monocyte-derived macrophages. We identified 110 proteins in culture supernatants of control (uninfected) and virus-infected cells. Differentially expressed cytoskeletal, enzymes, redox, and immunoregulatory protein classes were discovered and validated by Western blot tests. These included, but were not limited to, cystatin C, cystatin B, chitinase 3-like 1 protein, cofilin-1, l-plastin, superoxide dismutase, leukotriene A(4) hydrolase, and alpha-enolase. This study, using a unique proteomics platform, provides novel insights into virus-host cell interactions that likely affect the functional role of macrophages in HIV disease.
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PMID:Investigating the human immunodeficiency virus type 1-infected monocyte-derived macrophage secretome. 1732 Jan 37

A homeostatic balance exists between the cellular generation of oxidant species and endogenous antioxidants under normal physiological conditions. Human Immunodeficiency Virus (HIV) infection is known to affect this balance causing oxidative stress. However, the interaction of HIV infection with a substance abuse on cellular oxidant/antioxidant system is sparse. This study was designed in order to investigate the interactive effect of morphine abuse and Simian Immunodeficiency Virus/ Simian Human Immunodeficiency Virus (SIV/SHIV) infection on plasma oxidant/antioxidant balance in rhesus macaques. Six rhesus macaques adapted to morphine dependence (20 weeks) along with three controls were infected with mixture of SHIV(KU-1B), SHIV(89.6P), and SIV(17E-Fr). Plasma samples from morphine-dependent and control macaques were analyzed for an array of oxidative stress indices after 16 weeks of infection. Morphine-dependence significantly increased plasma malondialdehyde (MDA) and 8-isoprostane levels (8-fold and 2-fold), but these animals showed higher MDA and 8-isoprostane levels after viral infection (18-fold and 4-fold) which was directly correlated with increase in viral load and decline in CD4+ cells. Plasma glutathione (GSH) level depleted (55%) with morphine dependence that was further depleted (25%) by the infection. Activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were increased by 30% and 110%, respectively with morphine dependence, but that was decreased by the infection. Catalase (CAT) activity declined (25%) with morphine dependence that was further declined by infection. Our results clearly suggest that morphine interaction with SIV/SHIV infection causes higher oxidative tissue injury that might have implication in the pathogenesis of AIDS in morphine-dependent macaques.
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PMID:Interaction of SIV/SHIV infection and morphine on plasma oxidant/antioxidant balance in macaque. 1793

Oxidative stress is thought to contribute to the pathogenesis of HIV infection in humans. For example, CD4(+) T cells are particularly affected in HIV patients and oxidative stress may also contribute to impairment of neutrophil function in HIV/AIDS patients. Since cats infected with FIV develop many of the same immunological abnormalites as HIV-infected humans, we investigated effects of acute FIV infection on oxidative stress in cats. Cats were infected with a pathogenic strain of FIV and viral load, changes in neutrophil number, total blood glutathione, malondiadehye, antioxidant enzyme concentrations, and reduced glutathione (GSH) concentration in leukocytes were measured sequentially during the first 16 weeks of infection. We found that superoxide dismutase and glutathione peroxidase concentrations in whole blood increased significantly during acute FIV infection. In addition, neutrophil numbers increased significantly during this time period, though their intracellular GSH concentrations did not change. In contrast, the numbers of CD4(+) T cells decreased significantly and their intracellular GSH concentration increased significantly, while intracellular GSH concentrations were unchanged in CD8(+) T cells. However, by 16 weeks of infection, many of the abnormalities in oxidative balance had stabilized or returned to pre-inoculation values. These results suggest that acute infection with FIV causes oxidative stress in cats and that CD4(+) T cells appear to be preferentially affected. Further studies are required to determine whether early treatment with anti-oxidants may help ameliorate the decline in CD4(+) T cell number and function associated with acute FIV infection in cats.
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PMID:Oxidative stress during acute FIV infection in cats. 1807 1

HIV-1 Tat is considered to be one of key players to facilitate monocyte entry into the CNS, which is characteristic feature of AIDS-related encephalitis and dementia. This study was performed to determine the regulatory function of superoxide dismutase (SOD) on the HIV-1 Tat-induced signaling pathways leading to NF-kappaB activation, expression of adhesion molecules, and monocyte adhesion in CRT-MG human astroglioma cells by using cell-permeable SOD. When cell-permeable SOD was added to the culture medium of CRT-MG cells, it rapidly entered the cells in dose- and time-dependent manners. Treatment of astrocytes with cell-permeable SOD led to decrease in Tat-induced ROS generation as well as NF-kappaB activation. Cell-permeable SOD inhibited the activation of MAP kinases including ERK, JNK and p38 by HIV-1 Tat. Treatment of CRT-MG cells with cell-permeable SOD significantly inhibited protein and mRNA levels of ICAM-1 and VCAM-1 up-regulated by HIV-1 Tat, as measured by Western blot analysis and RT-PCR. Furthermore, enhanced adhesiveness of monocyte to astrocyte by HIV-1 Tat was significantly abrogated by pretreatment with cell-permeable SOD fusion proteins. These data indicate that SOD has a regulatory function for HIV-1 Tat-induced NF-kappaB activation in astrocytes and suggest that cell-permeable SOD can be used as a feasible therapeutic agent for regulation of ROS-related neurological diseases.
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PMID:Suppression of HIV-1 Tat-induced monocyte adhesiveness by a cell-permeable superoxide dismutase in astrocytes. 1816 Aug 48

A domain (RKKRRQRRR) derived from HIV-1 Tat is one of the most efficient protein transduction domains (PTD) for delivering macromolecules including proteins into cells and tissues. Antioxidant enzymes such as superoxide dismutase (SOD) and catalase are major cellular defenses against oxidative stress which results in various diseases including skin inflammation. In this study, we examined the effect of SOD fused with HIV-1 Tat PTD (Tat-SOD) on TPA-induced skin inflammation in mice. Topical application of Tat-SOD to mice ears 1h after TPA application once a day for 3 days dose-dependently inhibited TPA-induced ear edema in mice. Topical application on mice ears of Tat-SOD also suppressed TPA-induced expression of proinflammatory cytokines such as TNF-alpha, IL-1beta, and IL-6 as well as cyclooxygenase-2 (COX-2) and production of PGE(2). Furthermore, topical application of Tat-SOD resulted in significant reduction in activation of NF-kappaB and mitogen-activated protein kinases (MAPK) in the mice ears treated with TPA. These data demonstrates that Tat-SOD inhibits TPA-induced inflammation in mice by reducing the levels of expression of proinflammatory cytokines and enzymes regulated by the NF-kappaB and MAPK and can be used as a therapeutic agent against skin inflammation related to oxidative damage.
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PMID:Topical transduction of superoxide dismutase mediated by HIV-1 Tat protein transduction domain ameliorates 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice. 1816 93

The present study was undertaken to examine the state of intracellular components and leukocytes and the role of the lipid peroxidation (LPO) system and antioxidative defense (AOD) in the pathogenesis of HIV infection. The parameters of the enzymatic link of the antioxidative system and LPO processes and leukocytic intracellular components in 108 patients with HIV infection are presented. In the HIV-infected patients, the state of intracellular components of leukocytes showed a heterodirectional pattern. Thus, the values of myeloperoxidase and cationic protein exhibited a regular trend for a decrease with the maximum inhibition when secondary diseases occurred. The activity of acid phosphatase, glycogen and spontaneous HCT test increased with progression of the disease. The findings suggest that there are severe LPO disorders, as documented by a significant increase in its products forming at different stages of the peroxide cascade of hydroperoxides: malonic dialdehyde and dienic conjugates. The rate of LPO-AOD processes depends on the stage of the disease and the treatment performed. It is important to note that in HIV-infected patients the increased rate of LPO was followed by the considerably suppressed overall antioxidative activity of blood, catalase, and superoxide dismutase. The decrease in these parameters suggests a severe disturbance of the antioxidative system in different periods of the disease. The enhanced LPO activity in patients with HIV infection is likely to be one of the pathogenetic links of development of the disease and requires corrective therapy.
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PMID:[Leukocytic intracellular components and proantioxidative systems in HIV-infected patients]. 1835 22

Antioxidants significantly inhibit oxidative processes. The study seeks to determine the activity of endogenous antioxidants and CD4+ T-cell expression in HIV-serodiscordant-heterosexual partners. The case-control study had the following groups; A- (13 serodiscordant-seronegative subjects), B- (13 serodiscordant-seropositive subjects) and C/control- (13 healthy volunteers). CD4+ T-cell expression was determined using a FACScan (fluorescent activated cell sorting) flow cytometer. CAT (catalase), superoxide dismutase, glutathione peroxidase (GHPX) and glutathione S-transferase (GST) activities were assayed using spectrophotometer. The activities of SOD, GHPX, GST and CAT were significantly (P < 0.05) increased by 164.7% (0.090 +/- 0.032), 126% (662 +/- 96), 355.2% (22.023 +/- 1.4) and 119.1% (2.76 +/- 0.10), respectively, in group A when compared with B. The mean CD4+ T-cell (1348 +/- 142) showed a significant (P < 0.05) increase by 237% when compared with group B (400 +/- 182). Conversely, group B revealed a significant (P < 0.05) decrease in activity by 86.5% (CAT), 76.5% (SOD), 106.8% (GHPX) and 81.8% (GST) when compared with C. CD4+ T-cells in groups A and C (1390 +/- 190) did not show any significant decrease (3.11%). The antioxidant activity showed a positive correlation (P < 0.01, r = 0.89) with their respective CD4+ T-cells in groups A and C. Group B showed same positive correlation (P < 0.01, r = 0.76). These results show that high activity of endogenous antioxidants may have a protective role on CD4+ T-cells, which limits HIV infection.
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PMID:High plasma activity of endogenous antioxidants protect CD4+ T-cells in HIV-serodiscordant heterosexual partners in a Nigerian population. 1866 40

Although it has been widely suggested that oxidative stress contributes to the pathogenesis of HIV infection, salivary composition and its oxidative related aspects have never been studied in HIV patients, both HAART-treated and untreated. Human saliva and serum were collected and analyzed for various biochemical, redox related and immunological parameters from 43 consenting HIV-infected patients (20 untreated and 23 treated with HAART) and 20 healthy controls, age and gender matched. Saliva composition of HIV infected patients was completely altered but returned to normal following HAART. HIV patients had significantly-increased levels of oxidative stress damaging markers, compared to healthy controls. Carbonyl levels increased by 110% (p=0.005), and superoxide dismutase enzyme (SOD) and antioxidant capacity (ImAnOx) levels by 45% and 16% (0.035) respectively, but returned to normal levels in treated patients (p=0.005, p=0.03 and 0.02 respectively). Also, the significantly-altered salivary composition (pH and lactate dehydrogenase (LDH) enzyme) and concentration (calcium (Ca), magnesium (Mg), albumin, salivary total protein, secretory IgA) of HIV-infected patients reverted to normal following HAART treatment. Salivary analysis may be used for assessing patient status: treated vs untreated, based on the increase or decrease in the concentration of a given salivary parameter in the HIV-untreated group vs controls, and a return to normal following the HAART treatment. Salivary collection is simple, non-invasive and not associated with risk of infection spread. Antioxidants in HIV patients may be recommended, as well as local oral means aimed at resuming salivary functions compromised in HIV patients.
Curr HIV Res 2008 Sep
PMID:Effect of HAART on salivary composition and oxidative profile in HIV-infected patients. 1885 55

HIV-associated cognitive neurological disorders (HAND) prevail in the antiretroviral therapy era. Proteomics analysis of CSF revealed expression of Cu/Zn superoxide dismutase (Cu/Zn SOD) in Hispanic women with cognitive impairment (CI). We tested the hypothesis that there is reduced capacity of antioxidant enzymes in CI by measures of expression and activity of Cu/Zn SOD, catalase, and Se-glutathione peroxidase in HAND. Our results showed that the function of these antioxidants was decreased in the CSF and monocytes of women with CI. These findings have important implications regarding their possible contribution to oxidative stress and in the diagnosis and therapy for HAND.
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PMID:Antioxidant enzyme dysfunction in monocytes and CSF of Hispanic women with HIV-associated cognitive impairment. 1910 Oct 40


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