Redox response of the endogenous calcineurin inhibitor Adapt78

Narayan, Ananth; Stadel, Rebecca; Hahn, Amy B.; Bhoiwala, Dipti L.; Cornielle, Geysha; Sarazin, Erwin; Koleilat, Issam; Crawford, Dana R.

doi:10.1016/j.freeradbiomed.2005.03.036

Cited by 10 publications

(17 citation statements)

References 36 publications

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“…Combined with previous studies by Ryeom et al (2003) demonstrating its importance in T-cell activation and apoptosis, and in our laboratory demonstrating its involvement in T-lymphocyte isoform 4 (c). response to anti-CD3 plus anti-CD28 antibodies (Narayan et al, 2005), it is now clear that RCAN1 plays an important role in immune function. Ã Significant difference between isoform 4 vs. isoform 1 using a two-tailed Student's t-test at P o.05, with N = 3-4.…”

Section: Discussionmentioning

confidence: 99%

“…Its stimulation of IL-2 transcription here is a key mediator of T-cell activation and the subsequent autocrine loop proliferation that is so critical to adaptive immune response. Also, we observed that the stimulation of Jurkat and primary T-lymphocyte signaling leads to isoform 4 induction in a calcium, calcineurin, and reactive oxygen species (ROS)-dependent manner that is accompanied by IL-2 induction (Narayan et al, 2005). Ryeom et al (2003) investigated the role of RCAN1 in T-cells by assessing the induction of calcineurin-dependent proinflammatory genes in RCAN1-deficient mouse T-lymphocytes.…”

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confidence: 99%

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The calcineurin inhibitor RCAN1 is involved in cultured macrophage and in vivo immune response

Bhoiwala

Kannabiran

Hushmendy

et al. 2010

FEMS Immunology &Amp; Medical Microbiology

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Studies on the role of regulator of calcineurin 1 (RCAN1) in immunity are limited, but have demonstrated an involvement in T-lymphocyte function. Here, we expand these studies to macrophages and in vivo infection. The treatment of RAW and primary mouse macrophages with lipopolysaccharide from Escherichia coli strongly induced RCAN1 isoform 4 (RCAN1-4), but not isoform 1. RCAN1-4 induction involved calcium, calcineurin, and reactive oxygen species. Subsequent analysis with whole bacteria including gram-negative E. coli and gram-positive Staphylococcus aureus revealed strong RCAN1-4 inductions by both, and where tested, dependence on calcium. Staphylococcus aureus cell wall components peptidoglycan and lipoteichoic acid also strongly induced RCAN1-4. In vivo, a significant induction in the proinflammatory cytokines monocyte chemotactic protein-1, interleukin-6, interferon-γ, and tumor necrosis factor-α was observed in knockout (KO) lung vs. wild-type (WT) mice 7 days after nasal infection with Fransicella tularensis. This induction was not accompanied by a significant increase in F. tularensis burden in the KO lung. Additionally, a modest increase in respiratory burst activity in KO vs. WT macrophages was observed. Combined, these studies indicate that RCAN1 is involved in macrophage and the overall in vivo immune response, and provide additional evidence that RCAN1 plays an important role in cell immunity and infectious disease.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

The calcineurin inhibitor RCAN1 is involved in cultured macrophage and in vivo immune response

Bhoiwala

Kannabiran

Hushmendy

et al. 2010

FEMS Immunology &Amp; Medical Microbiology

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“…electrophoresed on an sodium dodecyl sulfate-polyacrylamide gel, electroblotted to nitrocellulose, and incubated with primary antibody followed by peroxidase-conjugated secondary antibody and signal development with Western light chemiluminescent substrate (Perkin Elmer, Boston, MA, USA) [28,34]. All signals were captured on film and quantified using the ImageJ program (National Institutes of Health, Bethesda, MD, USA).…”

Section: Efflux Back To Cytoplasmmentioning

confidence: 99%

“…1. RCAN1 protein inhibits calcineurin [26][27][28][29][30], a calcium-activated protein phosphatase that mediates many cellular functions, especially in the brain where it comprises more than 1% of the total protein and regulates neuronal apoptosis, N-methyl-D-aspartate receptor channels, neurite outgrowth, long-term memory and potentiation, neurotransmitter release, and tau dephosphorylation [30][31][32][33][34]. Under normal conditions, agonists that elevate intracellular calcium lead to activation of calcineurin, which dephosphorylates NF-AT, leading to its nuclear migration and activation of target genes.…”

Section: Introductionmentioning

confidence: 99%

Fish oil improves gene targets of Down syndrome in C57BL and BALB/c mice

et al. 2015

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“…Recently, we and others demonstrated that a Saccharomyces cerevisiae ortholog of RCAN1 is ubiquitinated by a rise in intracellular Ca 2+ , and exogenously expressed human RCAN1-4 is ubiquitinated in normal culture conditions (34)(35)(36). Moreover, oxidative stress induces a decrease in RCAN1-4 via an MG132-sensitive pathway in HeLa cells (37). Taken together, these findings raise the possibility that oxidative stress may induce a ubiquitin-mediated decrease in the protein level of RCAN1.…”

Section: Introductionmentioning

confidence: 76%

Oxidative stress-induced ubiquitination of RCAN1 mediated by SCFβ-TrCP ubiquitin ligase

Asada¹,

Ikeda²,

Nagao³

et al. 2008

Int J Mol Med

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Abstract. A change in the protein level of RCAN1 (DSCR1/ MCIP/Adapt78/CSP1) has been implicated in oxidative stressinduced cell death in neurons and in the pathogenesis of Alzheimer's disease. The pathogenic processes in neurodegenerative diseases are closely related to oxidative stress and the ubiquitin proteasome system (UPS). Therefore, we investigated whether oxidative stress induces a change in the protein level of RCAN1 through the UPS. H 2 O 2 induced ubiquitination of RCAN1 at the same concentrations as those causing a decrease in RCAN1 in HEK293T cells. ß-TrCP, the F-box protein component of SCF ubiquitin ligase, interacted with RCAN1 in response to H 2 O 2 stimulation. Although FBW4, another F-box protein, interacted with RCAN1, its interaction was independent of H 2 O 2 stimulation. In vitro ubiquitination assay showed that SCF ß-TrCP but not SCF FBW4 increased ubiquitination of RCAN1, dependent on H 2 O 2 stimulation. In addition, knockdown of ß-TrCP by siRNA abolished the H 2 O 2 -induced decrease in RCAN1 in HEK293T cells. We further examined whether RCAN1 undergoes ubiquitination by H 2 O 2 in primary neurons, similarly to that in HEK293T cells. An H 2 O 2 -induced decrease in RCAN1 was exhibited also in hippocampal and cortical neurons. Ubiquitination of RCAN1 was induced by 500 μM H 2 O 2 , the concentration at which H 2 O 2 induced a decrease in RCAN1 in primary neurons. These results suggest that H 2 O 2 induces SCF ß-TrCP -mediated ubiquitination of RCAN1, leading to a decrease in the protein level of RCAN1.

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Redox response of the endogenous calcineurin inhibitor Adapt78

Cited by 10 publications

References 36 publications

The calcineurin inhibitor RCAN1 is involved in cultured macrophage and in vivo immune response

The calcineurin inhibitor RCAN1 is involved in cultured macrophage and in vivo immune response

Fish oil improves gene targets of Down syndrome in C57BL and BALB/c mice

Oxidative stress-induced ubiquitination of RCAN1 mediated by SCFβ-TrCP ubiquitin ligase

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