Calmodulin involvement in stress-activated nuclear localization of albumin in JB6 epithelial cells

Thomas J. Weber, Sewite Negash, Heather Smallwood, Kenneth S. Ramos, Brian D. Thrall, Thomas C. Squier

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

We report that albumin is translocated to the nucleus in response to oxidative stress. Prior measurements have demonstrated that in concert with known transcription factors albumin binds to an antioxidant response element, which controls the expression of glutathione S-transferase and other antioxidant enzymes that function to mediate adaptive cellular responses [Holderman, M. T., Miller, K. P., Dangott, L. J., and Ramos, K. S. (2002) Mol. Pharmacol. 61, 1174-1183]. To investigate the mechanisms underlying this adaptive cell response, we have identified linkages between calcium signaling and the nuclear translocation of albumin in JB6 epithelial cells. Under resting conditions, albumin and the calcium regulatory protein calmodulin (CaM) co-immunoprecipitate using antibodies against either protein, indicating a tight association. Calcium activation of CaM disrupts the association between CaM and albumin, suggesting that transient increases in cytosolic calcium levels function to mobilize intracellular albumin to facilitate its translocation into the nucleus. Likewise, nuclear translocation of albumin is induced by exposure of cells to hydrogen peroxide or a phorbol ester, indicating a functional linkage between reactive oxygen species, calcium, and PKC-signaling pathways. Inclusion of an antioxidant enzyme (i.e., superoxide dismutase) blocks nuclear translocation, suggesting that the oxidation of sensitive proteins functions to coordinate the adaptive cellular response. These results suggest that elevated calcium transients and associated increases in reactive oxygen species contribute to adaptive cellular responses through the mobilization and nuclear translocation of cellular albumin.

Original languageEnglish (US)
Pages (from-to)7443-7450
Number of pages8
JournalBiochemistry
Volume43
Issue number23
DOIs
StatePublished - Jun 15 2004
Externally publishedYes

Fingerprint

Calmodulin
Albumins
Epithelial Cells
Calcium
Calcium Signaling
Reactive Oxygen Species
Antioxidants
Antioxidant Response Elements
Association reactions
Proteins
Oxidative stress
Phorbol Esters
Enzymes
Glutathione Transferase
Hydrogen Peroxide
Superoxide Dismutase
Oxidative Stress
Transcription Factors
Chemical activation
Oxidation

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Calmodulin involvement in stress-activated nuclear localization of albumin in JB6 epithelial cells. / Weber, Thomas J.; Negash, Sewite; Smallwood, Heather; Ramos, Kenneth S.; Thrall, Brian D.; Squier, Thomas C.

In: Biochemistry, Vol. 43, No. 23, 15.06.2004, p. 7443-7450.

Research output: Contribution to journalArticle

Weber, Thomas J. ; Negash, Sewite ; Smallwood, Heather ; Ramos, Kenneth S. ; Thrall, Brian D. ; Squier, Thomas C. / Calmodulin involvement in stress-activated nuclear localization of albumin in JB6 epithelial cells. In: Biochemistry. 2004 ; Vol. 43, No. 23. pp. 7443-7450.
@article{c0bbb51336214561a179bb0277d3a42c,
title = "Calmodulin involvement in stress-activated nuclear localization of albumin in JB6 epithelial cells",
abstract = "We report that albumin is translocated to the nucleus in response to oxidative stress. Prior measurements have demonstrated that in concert with known transcription factors albumin binds to an antioxidant response element, which controls the expression of glutathione S-transferase and other antioxidant enzymes that function to mediate adaptive cellular responses [Holderman, M. T., Miller, K. P., Dangott, L. J., and Ramos, K. S. (2002) Mol. Pharmacol. 61, 1174-1183]. To investigate the mechanisms underlying this adaptive cell response, we have identified linkages between calcium signaling and the nuclear translocation of albumin in JB6 epithelial cells. Under resting conditions, albumin and the calcium regulatory protein calmodulin (CaM) co-immunoprecipitate using antibodies against either protein, indicating a tight association. Calcium activation of CaM disrupts the association between CaM and albumin, suggesting that transient increases in cytosolic calcium levels function to mobilize intracellular albumin to facilitate its translocation into the nucleus. Likewise, nuclear translocation of albumin is induced by exposure of cells to hydrogen peroxide or a phorbol ester, indicating a functional linkage between reactive oxygen species, calcium, and PKC-signaling pathways. Inclusion of an antioxidant enzyme (i.e., superoxide dismutase) blocks nuclear translocation, suggesting that the oxidation of sensitive proteins functions to coordinate the adaptive cellular response. These results suggest that elevated calcium transients and associated increases in reactive oxygen species contribute to adaptive cellular responses through the mobilization and nuclear translocation of cellular albumin.",
author = "Weber, {Thomas J.} and Sewite Negash and Heather Smallwood and Ramos, {Kenneth S.} and Thrall, {Brian D.} and Squier, {Thomas C.}",
year = "2004",
month = "6",
day = "15",
doi = "10.1021/bi049731s",
language = "English (US)",
volume = "43",
pages = "7443--7450",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "23",

}

TY - JOUR

T1 - Calmodulin involvement in stress-activated nuclear localization of albumin in JB6 epithelial cells

AU - Weber, Thomas J.

AU - Negash, Sewite

AU - Smallwood, Heather

AU - Ramos, Kenneth S.

AU - Thrall, Brian D.

AU - Squier, Thomas C.

PY - 2004/6/15

Y1 - 2004/6/15

N2 - We report that albumin is translocated to the nucleus in response to oxidative stress. Prior measurements have demonstrated that in concert with known transcription factors albumin binds to an antioxidant response element, which controls the expression of glutathione S-transferase and other antioxidant enzymes that function to mediate adaptive cellular responses [Holderman, M. T., Miller, K. P., Dangott, L. J., and Ramos, K. S. (2002) Mol. Pharmacol. 61, 1174-1183]. To investigate the mechanisms underlying this adaptive cell response, we have identified linkages between calcium signaling and the nuclear translocation of albumin in JB6 epithelial cells. Under resting conditions, albumin and the calcium regulatory protein calmodulin (CaM) co-immunoprecipitate using antibodies against either protein, indicating a tight association. Calcium activation of CaM disrupts the association between CaM and albumin, suggesting that transient increases in cytosolic calcium levels function to mobilize intracellular albumin to facilitate its translocation into the nucleus. Likewise, nuclear translocation of albumin is induced by exposure of cells to hydrogen peroxide or a phorbol ester, indicating a functional linkage between reactive oxygen species, calcium, and PKC-signaling pathways. Inclusion of an antioxidant enzyme (i.e., superoxide dismutase) blocks nuclear translocation, suggesting that the oxidation of sensitive proteins functions to coordinate the adaptive cellular response. These results suggest that elevated calcium transients and associated increases in reactive oxygen species contribute to adaptive cellular responses through the mobilization and nuclear translocation of cellular albumin.

AB - We report that albumin is translocated to the nucleus in response to oxidative stress. Prior measurements have demonstrated that in concert with known transcription factors albumin binds to an antioxidant response element, which controls the expression of glutathione S-transferase and other antioxidant enzymes that function to mediate adaptive cellular responses [Holderman, M. T., Miller, K. P., Dangott, L. J., and Ramos, K. S. (2002) Mol. Pharmacol. 61, 1174-1183]. To investigate the mechanisms underlying this adaptive cell response, we have identified linkages between calcium signaling and the nuclear translocation of albumin in JB6 epithelial cells. Under resting conditions, albumin and the calcium regulatory protein calmodulin (CaM) co-immunoprecipitate using antibodies against either protein, indicating a tight association. Calcium activation of CaM disrupts the association between CaM and albumin, suggesting that transient increases in cytosolic calcium levels function to mobilize intracellular albumin to facilitate its translocation into the nucleus. Likewise, nuclear translocation of albumin is induced by exposure of cells to hydrogen peroxide or a phorbol ester, indicating a functional linkage between reactive oxygen species, calcium, and PKC-signaling pathways. Inclusion of an antioxidant enzyme (i.e., superoxide dismutase) blocks nuclear translocation, suggesting that the oxidation of sensitive proteins functions to coordinate the adaptive cellular response. These results suggest that elevated calcium transients and associated increases in reactive oxygen species contribute to adaptive cellular responses through the mobilization and nuclear translocation of cellular albumin.

UR - http://www.scopus.com/inward/record.url?scp=2942585061&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2942585061&partnerID=8YFLogxK

U2 - 10.1021/bi049731s

DO - 10.1021/bi049731s

M3 - Article

VL - 43

SP - 7443

EP - 7450

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 23

ER -