Redox response of the endogenous calcineurin inhibitor Adapt78

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

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Adapt78 (DSCR1/calcipressin/MCIP1) is a potent natural inhibitor of calcineurin, an important intracellular phosphatase that mediates many cellular responses to calcium. We previously reported two major cytosolic isoforms (1 and 4) of Adapt78, and that isoform 4 is an oxidative and calcium stress-response protein. Using a higher cell culture density and new antibody, we again observed that both major isoforms localized to the cytosol, but a significant level of isoform 4 (but not isoform 1) was also detected in the nucleus where it was present in the nonsoluble region and not associated with RNA. Exposure of cells to hydrogen peroxide led to the significant loss of isoform 4 from the nucleus with a moderate increase in cytosolic localization. The change in isoform 4 phosphorylation state in response to oxidative stress, characterized by a loss of the lesser (hypo) phosphorylated Adapt78, was not due to accelerated degradation, although general Adapt78 degradation was proteosome mediated. Finally, stimulation of Jurkat and primary T-lymphocyte signaling led to isoform 4 induction. This induction was BAPTA, diphenylene iodonium, and N-acetylcysteine inhibitable, and accompanied by induction of the classic immune response mediator and calcineurin-pathway-stimulated interleukin-2. These studies reveal new redox-related activities for Adapt78 isoform 4, which may contribute to its known calcineurin-regulating and cytoprotective activities, and further suggest that Adapt78 plays a role in basic T-cell response.

Original languageEnglish (US)
Pages (from-to)719-727
Number of pages9
JournalFree Radical Biology and Medicine
Volume39
Issue number6
DOIs
StatePublished - Sep 15 2005
Externally publishedYes

Fingerprint

Oxidation-Reduction
Protein Isoforms
T-cells
Calcineurin
Oxidative Stress
Calcium
T-Lymphocytes
Calcineurin Inhibitors
Degradation
Phosphorylation
Oxidative stress
Acetylcysteine
Heat-Shock Proteins
Cell culture
Phosphoric Monoester Hydrolases
Cytosol
Hydrogen Peroxide
Interleukin-2
Cell Culture Techniques
Cell Count

Keywords

  • Calcineurin
  • Free radicals
  • Hydrogen peroxide
  • Oxidative stress
  • Redox
  • Stress-response
  • Subcellular localization
  • T-cell response

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Cite this

Narayan, A. V., Stadel, R., Hahn, A. B., Bhoiwala, D. L., Cornielle, G., Sarazin, E., ... Crawford, D. R. (2005). Redox response of the endogenous calcineurin inhibitor Adapt78. Free Radical Biology and Medicine, 39(6), 719-727. https://doi.org/10.1016/j.freeradbiomed.2005.03.036

Redox response of the endogenous calcineurin inhibitor Adapt78. / Narayan, Ananth V.; Stadel, Rebecca; Hahn, Amy B.; Bhoiwala, Dipti L.; Cornielle, Geysha; Sarazin, Erwin; Koleilat, Issam; Crawford, Dana R.

In: Free Radical Biology and Medicine, Vol. 39, No. 6, 15.09.2005, p. 719-727.

Research output: Contribution to journalArticle

Narayan, AV, Stadel, R, Hahn, AB, Bhoiwala, DL, Cornielle, G, Sarazin, E, Koleilat, I & Crawford, DR 2005, 'Redox response of the endogenous calcineurin inhibitor Adapt78', Free Radical Biology and Medicine, vol. 39, no. 6, pp. 719-727. https://doi.org/10.1016/j.freeradbiomed.2005.03.036
Narayan AV, Stadel R, Hahn AB, Bhoiwala DL, Cornielle G, Sarazin E et al. Redox response of the endogenous calcineurin inhibitor Adapt78. Free Radical Biology and Medicine. 2005 Sep 15;39(6):719-727. https://doi.org/10.1016/j.freeradbiomed.2005.03.036
Narayan, Ananth V. ; Stadel, Rebecca ; Hahn, Amy B. ; Bhoiwala, Dipti L. ; Cornielle, Geysha ; Sarazin, Erwin ; Koleilat, Issam ; Crawford, Dana R. / Redox response of the endogenous calcineurin inhibitor Adapt78. In: Free Radical Biology and Medicine. 2005 ; Vol. 39, No. 6. pp. 719-727.
@article{d87a6a02e762478692331022a683f2d1,
title = "Redox response of the endogenous calcineurin inhibitor Adapt78",
abstract = "Adapt78 (DSCR1/calcipressin/MCIP1) is a potent natural inhibitor of calcineurin, an important intracellular phosphatase that mediates many cellular responses to calcium. We previously reported two major cytosolic isoforms (1 and 4) of Adapt78, and that isoform 4 is an oxidative and calcium stress-response protein. Using a higher cell culture density and new antibody, we again observed that both major isoforms localized to the cytosol, but a significant level of isoform 4 (but not isoform 1) was also detected in the nucleus where it was present in the nonsoluble region and not associated with RNA. Exposure of cells to hydrogen peroxide led to the significant loss of isoform 4 from the nucleus with a moderate increase in cytosolic localization. The change in isoform 4 phosphorylation state in response to oxidative stress, characterized by a loss of the lesser (hypo) phosphorylated Adapt78, was not due to accelerated degradation, although general Adapt78 degradation was proteosome mediated. Finally, stimulation of Jurkat and primary T-lymphocyte signaling led to isoform 4 induction. This induction was BAPTA, diphenylene iodonium, and N-acetylcysteine inhibitable, and accompanied by induction of the classic immune response mediator and calcineurin-pathway-stimulated interleukin-2. These studies reveal new redox-related activities for Adapt78 isoform 4, which may contribute to its known calcineurin-regulating and cytoprotective activities, and further suggest that Adapt78 plays a role in basic T-cell response.",
keywords = "Calcineurin, Free radicals, Hydrogen peroxide, Oxidative stress, Redox, Stress-response, Subcellular localization, T-cell response",
author = "Narayan, {Ananth V.} and Rebecca Stadel and Hahn, {Amy B.} and Bhoiwala, {Dipti L.} and Geysha Cornielle and Erwin Sarazin and Issam Koleilat and Crawford, {Dana R.}",
year = "2005",
month = "9",
day = "15",
doi = "10.1016/j.freeradbiomed.2005.03.036",
language = "English (US)",
volume = "39",
pages = "719--727",
journal = "Free Radical Biology and Medicine",
issn = "0891-5849",
publisher = "Elsevier Inc.",
number = "6",

}

TY - JOUR

T1 - Redox response of the endogenous calcineurin inhibitor Adapt78

AU - Narayan, Ananth V.

AU - Stadel, Rebecca

AU - Hahn, Amy B.

AU - Bhoiwala, Dipti L.

AU - Cornielle, Geysha

AU - Sarazin, Erwin

AU - Koleilat, Issam

AU - Crawford, Dana R.

PY - 2005/9/15

Y1 - 2005/9/15

N2 - Adapt78 (DSCR1/calcipressin/MCIP1) is a potent natural inhibitor of calcineurin, an important intracellular phosphatase that mediates many cellular responses to calcium. We previously reported two major cytosolic isoforms (1 and 4) of Adapt78, and that isoform 4 is an oxidative and calcium stress-response protein. Using a higher cell culture density and new antibody, we again observed that both major isoforms localized to the cytosol, but a significant level of isoform 4 (but not isoform 1) was also detected in the nucleus where it was present in the nonsoluble region and not associated with RNA. Exposure of cells to hydrogen peroxide led to the significant loss of isoform 4 from the nucleus with a moderate increase in cytosolic localization. The change in isoform 4 phosphorylation state in response to oxidative stress, characterized by a loss of the lesser (hypo) phosphorylated Adapt78, was not due to accelerated degradation, although general Adapt78 degradation was proteosome mediated. Finally, stimulation of Jurkat and primary T-lymphocyte signaling led to isoform 4 induction. This induction was BAPTA, diphenylene iodonium, and N-acetylcysteine inhibitable, and accompanied by induction of the classic immune response mediator and calcineurin-pathway-stimulated interleukin-2. These studies reveal new redox-related activities for Adapt78 isoform 4, which may contribute to its known calcineurin-regulating and cytoprotective activities, and further suggest that Adapt78 plays a role in basic T-cell response.

AB - Adapt78 (DSCR1/calcipressin/MCIP1) is a potent natural inhibitor of calcineurin, an important intracellular phosphatase that mediates many cellular responses to calcium. We previously reported two major cytosolic isoforms (1 and 4) of Adapt78, and that isoform 4 is an oxidative and calcium stress-response protein. Using a higher cell culture density and new antibody, we again observed that both major isoforms localized to the cytosol, but a significant level of isoform 4 (but not isoform 1) was also detected in the nucleus where it was present in the nonsoluble region and not associated with RNA. Exposure of cells to hydrogen peroxide led to the significant loss of isoform 4 from the nucleus with a moderate increase in cytosolic localization. The change in isoform 4 phosphorylation state in response to oxidative stress, characterized by a loss of the lesser (hypo) phosphorylated Adapt78, was not due to accelerated degradation, although general Adapt78 degradation was proteosome mediated. Finally, stimulation of Jurkat and primary T-lymphocyte signaling led to isoform 4 induction. This induction was BAPTA, diphenylene iodonium, and N-acetylcysteine inhibitable, and accompanied by induction of the classic immune response mediator and calcineurin-pathway-stimulated interleukin-2. These studies reveal new redox-related activities for Adapt78 isoform 4, which may contribute to its known calcineurin-regulating and cytoprotective activities, and further suggest that Adapt78 plays a role in basic T-cell response.

KW - Calcineurin

KW - Free radicals

KW - Hydrogen peroxide

KW - Oxidative stress

KW - Redox

KW - Stress-response

KW - Subcellular localization

KW - T-cell response

UR - http://www.scopus.com/inward/record.url?scp=23744440047&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=23744440047&partnerID=8YFLogxK

U2 - 10.1016/j.freeradbiomed.2005.03.036

DO - 10.1016/j.freeradbiomed.2005.03.036

M3 - Article

C2 - 16109302

AN - SCOPUS:23744440047

VL - 39

SP - 719

EP - 727

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

SN - 0891-5849

IS - 6

ER -