Thioredoxin Reductase-1 Negatively Regulates HIV-1 Transactivating Protein Tat-dependent Transcription in Human Macrophages

Kalantari, Parisa; Narayan, Vivek; Natarajan, Sathish Kumar; Muralidhar, K.; Gandhi, Ujjawal H.; Vunta, Hema; Henderson, Andrew J.; Prabhu, K. Sandeep

doi:10.1074/jbc.m807403200

Cited by 67 publications

(76 citation statements)

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“…To what extent these cytoprotective and metabolic changes contribute to both cancer preventive and tumor promoting functions of TR1 remains to be established. In addition to its role in cancer, TR1 has been recently implicated in mediating the important role of Se in immune function and prevention of HIV infection (166). TR1 has been proposed to negatively regulate the activity of the HIV-1 encoded transcriptional activator, Tat, in human macrophages by reducing disulfide bonds in a Cys-rich motif of Tat involved in HIV-1 transactivation.…”

Section: Thioredoxin Reductasesmentioning

confidence: 99%

Selenoproteins: Molecular Pathways and Physiological Roles

Labunskyy

Hatfield

Gladyshev³

2014

Physiological Reviews

1,028

835

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Selenium is an essential micronutrient with important functions in human health and relevance to several pathophysiological conditions. The biological effects of selenium are largely mediated by selenium-containing proteins (selenoproteins) that are present in all three domains of life. Although selenoproteins represent diverse molecular pathways and biological functions, all these proteins contain at least one selenocysteine (Sec), a seleniumcontaining amino acid, and most serve oxidoreductase functions. Sec is cotranslationally inserted into nascent polypeptide chains in response to the UGA codon, whose normal function is to terminate translation. To decode UGA as Sec, organisms evolved the Sec insertion machinery that allows incorporation of this amino acid at specific UGA codons in a process requiring a cis-acting Sec insertion sequence (SECIS) element. Although the basic mechanisms of Sec synthesis and insertion into proteins in both prokaryotes and eukaryotes have been studied in great detail, the identity and functions of many selenoproteins remain largely unknown. In the last decade, there has been significant progress in characterizing selenoproteins and selenoproteomes and understanding their physiological functions. We discuss current knowledge about how these unique proteins perform their functions at the molecular level and highlight new insights into the roles that selenoproteins play in human health.

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Section: Thioredoxin Reductasesmentioning

confidence: 99%

Selenoproteins: Molecular Pathways and Physiological Roles

Labunskyy

Hatfield

Gladyshev³

2014

Physiological Reviews

1,028

835

View full text Add to dashboard Cite

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“…These include LPS (Wang et al, 2007), Aβ peptide (Zhang et al, 2010) and IL-1β (Sharma et al, 2007). In addition, it is known that Trx1 negatively regulates the HIV-encoded transcriptional activator, Tat, in macrophages (Kalantari et al, 2008). siRNA knockdown of Trx1 increases HIV replication independently of NF-κB activation through targeting the two disulphide bonds in Tat that are actively involved in transactivation.…”

mentioning

confidence: 99%

Microglia antioxidant systems and redox signalling

Vilhardt¹,

Haslund-vinding

Jaquet³

et al. 2016

British J Pharmacology

108

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For many years, microglia, the resident CNS macrophages, have been considered only in the context of pathology, but microglia are also glial cells with important physiological functions. Microglia-derived oxidant production by NADPH oxidase (NOX2) is implicated in many CNS disorders. Oxidants do not stand alone, however, and are not always pernicious. We discuss in general terms, and where available in microglia, GSH synthesis and relation to cystine import and glutamate export, and the thioredoxin system as the most important antioxidative defence mechanism, and further, we discuss in the context of protein thiolation of target redox proteins the necessity for tightly localized, timed and confined oxidant production to work in concert with antioxidant proteins to promote redox signalling. NOX2-mediated redox signalling modulates the acquisition of the classical or alternative microglia activation phenotypes by regulating major transcriptional programs mediated through NF-κB and Nrf2, major regulators of the inflammatory and antioxidant response respectively. As both antioxidants and NOX-derived oxidants are co-secreted, in some instances redox signalling may extend to neighboring cells through modification of surface or cytosolic target proteins. We consider a role for microglia NOX-derived oxidants in paracrine modification of synaptic function through long term depression and in the communication with the adaptive immune system. There is little doubt that a continued foray into the functions of the antioxidant response in microglia will reveal antioxidant proteins as dynamic players in redox signalling, which in concert with NOX-derived oxidants fulfil important roles in the autocrine or paracrine regulation of essential enzymes or transcriptional programs. LINKED ARTICLESThis article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc Abbreviations Aβ, amyloid-β peptide 1-42; DAMP, damage-associated molecular pattern molecules; GCL, glutamate cysteine ligase; GPx, GSH peroxidase; HNE, 4-hydroxy-2-nonenal; HO-1, haem oxygenase-1; KEAP1, Kelch-like ECH-associated protein; LTD, long-term depression; PLA 2 , phospholipase A 2 ; Prx, peroxiredoxins; Trx, thioredoxin; TrxR, thioredoxin reductase; xCT, cystine-glutamate exchanger IntroductionMicroglia, the resident immune cells of the brain, are exquisitely sensitive cells, which through a large and unique repertoire of sensing cell surface receptors (Hickman et al., 2013) responding to ligands of exogenous or endogenous nature (Kettenmann et al., 2013) continuously survey the brain parenchyma for even the smallest deviation from homeostasis. When the fine, motile processes of microglia encounter a problem, microglia assume an activation phenotype adapted to the quick resolution of damage and return to homeostasis. If instigating insults cannot be resolved, chronic microglia activation ensues. The differing nature of...

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“…Positively Tat-regulating factors such as CCNT1, protein phospatase 1(PP1), and p300/CBP did not have lower expression levels in latent cells compared with normal cells, suggesting that the basal expression of these factors may not be associated with latent infection [47,48]. Negatively Tat-regulating factors including BanF1, BRD7, and thioredoxin reductase-1 (TXNRD1) did not show consistent differences in their expression patterns between latent and normal cells [49][50][51]. Of these factors, only NUCKS1, as a positively Tat-regulating factor, was expressed at a lower level in latently infected cells than in normal parent cells ( Figure 6A and B).…”

Section: Discussionmentioning

confidence: 99%