Vagal system impairment in HIV-positive patients with chronic hepatitis C: has hepatic glutathione deficiency a pathogenetic role?

Bárbaro, Giuseppe; Lorenzo, G. Di; Soldini, Maurizio; Bellomo, Giorgio; Belloni, G; Grisorio, Benvenuto; Rizzo, Giovanni; Cadario, F; Barbarini, Giorgio

doi:10.1016/s0168-8278(98)81058-1

Cited by 3 publications

(2 citation statements)

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“…A similar decline in GSH content has been found in the liver and erythrocytes of HIVϩ individuals (34,65). Hepatic GSH depletion is particularly interesting, as liver serves as a reservoir for HIV, and various cells found in liver, such as Kupffer cells, lymphocytes, sinusoidal endothelial cells, and even the hepatocytes themselves, can be infected by the virus (66).…”

Section: Discussionmentioning

confidence: 62%

Molecular Mechanism of Decreased Glutathione Content in Human Immunodeficiency Virus Type 1 Tat-transgenic Mice

Choi¹,

Liu²,

Kundu³

et al. 2000

Journal of Biological Chemistry

153

105

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Human immunodeficiency virus (HIV) progressively depletes GSH content in humans.Although the accumulated evidence suggests a role of decreased GSH in the pathogenesis of HIV, significant controversy remains concerning the mechanism of GSH depletion, especially in regard to envisioning appropriate therapeutic strategies to help compensate for such decreased antioxidant capacity. Tat, a transactivator encoded by HIV, is sufficient to cause GSH depletion in vitro and is implicated in AIDS-associated Kaposi's sarcoma and B cell lymphoma. In this study, we report a decrease in GSH biosynthesis with Tat, using HIV-1 Tat transgenic (Tat؉) mice. A significant decline in the total intracellular GSH content in liver and erythrocytes of Tat؉ mice was accompanied by decreased ␥-glutamylcysteine synthetase regulatory subunit mRNA and protein content, which resulted in an increased sensitivity of ␥-glutamylcysteine synthetase to feedback inhibition by GSH. Further study revealed a significant reduction in the activity of GSH synthetase in liver of Tat؉ mice, which was linearly associated with their GSH content. Therefore, Tat appears to decrease GSH in vivo, at least partially, through modulation of GSH biosynthetic enzymes. Human immunodeficiency virus (HIV)1 infection is associated with a systemic decrease in the GSH content in humans (1, 2). Such biochemical alteration appears to be a direct consequence of retroviral infection rather than a late and indirect consequence of advanced disease state, is progressive in nature, and often occurs in the absence of any symptoms associated with AIDS (2-5). The importance of this decreased GSH is suggested by the fact that decreased GSH can enhance HIV expression via activation of NF-B (4, 6, 7) and contribute to diverse immune dysfunctions found in AIDS, including the loss of CD4ϩ T lymphocytes via apoptosis (8 -11). In fact, such decline in the GSH content may play a role in the increased drug toxicity and oxidative damage, often found in HIV-infected individuals (12-15). Furthermore, increased GSH or other sulfhydryl compounds can inhibit viral replication (7, 16), HIV-1 reverse transcriptase activity (16,17), and the late stage of viral expression (18). GSH content may even predict the survival of HIV-seropositive (HIVϩ) individuals (19,20). Therefore, it is perhaps crucial to determine whether this decrease in GSH occurs through an accelerated loss of GSH or specific modulation of its synthesis, especially as it relates to potential therapeutic strategies to compensate for such decreased antioxidant capacity. However, despite over a decade of intensive research on this subject, the exact mechanism(s) causing decreased GSH content with HIV remains unclear.Cells maintain their high GSH content in part by reducing GSSG back to GSH, preventing the loss of GSH as GSSG (12). Also, GSH is synthesized from its amino acid constituents via two consecutive reactions catalyzed by ␥-glutamylcysteine synthetase (GCS; glutamate-cysteine ligase, EC 6.3.2.2) and GSH synthetase (GS; EC6.3.2.3). I...

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Section: Discussionmentioning

confidence: 62%

Molecular Mechanism of Decreased Glutathione Content in Human Immunodeficiency Virus Type 1 Tat-transgenic Mice

Choi¹,

Liu²,

Kundu³

et al. 2000

Journal of Biological Chemistry

153

105

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“…Anna Teresa Palamara, Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Universita ' di Roma ' Tor Vergata ', Via di Tor Vergata 135, 00139, Rome, Italy. E-mail : Palamara!Med.Uniroma2.it Barbaro et al, 1996), as well as in the lungs of influenza virus-infected mice (Hennet, Peterhans and Stocker, 1992). The mechanism by which different viruses are able to alter the intracellular redox state and the role of an oxidative environment in viral replication needs to be fully elucidated and it is still a matter of discussion.…”

Section: Introductionmentioning

confidence: 99%

Imbalance in Corneal Redox State during Herpes Simplex Virus 1-induced Keratitis in Rabbits. Effectiveness of Exogenous Glutathione Supply

Nucci

Palamara

Ciriolo

et al. 2000

Experimental Eye Research

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Update of research and management of hepatitis B

Okanoue¹,

Minami²

2006

J Gastroenterol

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and the mutation of precore and core promoter regions. 7,23 Most HBV carriers in Asian countries have resulted from maternal transmission of the infection during early childhood, and around 80% of the carriers show natural seroconversion from a hepatitis B e antigen (HBeAg)-positive state to an HBe antibody (HBeAb)-positive state before 25 years of age. Furthermore, HBeAg to HBeAb seroconversion frequently occurs in chronic hepatitis patients with a high serum alanine aminotransferase (ALT) level. Thus, it is important to clarify the natural course of HBV carriers before antiviral treatment. This article focuses on the recent advances in basic research of HBV and suggests a strategy of antiviral therapy for chronic hepatitis B patients. HBV genotypeThere are currently eight HBV subgroups based on genetic differences. HBV genotypes A, B, C, and D were first classified by an intergroup divergence of more than 8%. 1 HBV genotypes E and F were then identified, 2 followed by recent reports of genotypes G and H. 3,4 One cannot discriminate these genotypes by four serological subtypes (adw, adr, ayw, ayr) of HBV, which are classified by antigenic determinants of the hepatitis B surface antigen, but a there is a partial correlation between genotypes and serotypes (Table 1). There are also a few reports on a serological method for determining HBV genotypes using several monoclonal antibodies to preS2 and S proteins. 24,25 These HBV genotypes show a close relation to ethnicity (Table 1); more importantly, recent investigations have revealed associations between HBV genotypes and clinical features of the infection.Two major genotypes, HBV/B and HBV/C, prevail in East Asia including Japan. HBV genotype C was more prevalent than genotype B in cirrhotic patients in Japan, 5,26 China, 27 and Taiwan. 28 Another study from

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Vagal system impairment in HIV-positive patients with chronic hepatitis C: has hepatic glutathione deficiency a pathogenetic role?

Cited by 3 publications

References 0 publications

Molecular Mechanism of Decreased Glutathione Content in Human Immunodeficiency Virus Type 1 Tat-transgenic Mice

Molecular Mechanism of Decreased Glutathione Content in Human Immunodeficiency Virus Type 1 Tat-transgenic Mice

Imbalance in Corneal Redox State during Herpes Simplex Virus 1-induced Keratitis in Rabbits. Effectiveness of Exogenous Glutathione Supply

Update of research and management of hepatitis B

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