Increased covalent binding of acetaldehyde to calmodulin in the presence of calcium

Richard B. Jennett, Abbas Saffari-Fard, Michael Floyd Sorrell, Scott L. Smith, Dean J. Tuma

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The regulatory protein, calmodulin, undergoes major conformational changes in response to changes in intracellular calcium concentration. Furthermore, calmodulin has been reported to have lysine residues which markedly increase their reactivity toward electrophilic substances in the calcium-loaded state. We found that calmodulin formed two or three times more stable adducts with acetaldehyde in the calcium-loaded state as compared to the calcium-free state. Competition-binding studies showed that calmodulin could preferentially compete with albumin for acetaldehyde in the presence, but not in the absence, of calcium. When calmodulin was in the calcium-loaded state, trifluoperazine, an inhibitor of calmodulin activity, significantly decreased the stable binding of acetaldehyde to the protein, whereas in the calcium-free state, minimal effects on binding were observed. Since calmodulin is involved in regulation of multiple important processes in the cell, it is possible that acetaldehyde-calmodulin adducts could contribute to liver injury by perturbation of calcium-dependent homeostatic mechanisms within the hepatocyte.

Original languageEnglish (US)
Pages (from-to)1461-1466
Number of pages6
JournalLife Sciences
Volume45
Issue number16
DOIs
StatePublished - 1989

Fingerprint

Acetaldehyde
Calmodulin
Calcium
Trifluoperazine
Liver
Lysine
Hepatocytes
Albumins
Proteins
Wounds and Injuries

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Increased covalent binding of acetaldehyde to calmodulin in the presence of calcium. / Jennett, Richard B.; Saffari-Fard, Abbas; Sorrell, Michael Floyd; Smith, Scott L.; Tuma, Dean J.

In: Life Sciences, Vol. 45, No. 16, 1989, p. 1461-1466.

Research output: Contribution to journalArticle

Jennett, Richard B. ; Saffari-Fard, Abbas ; Sorrell, Michael Floyd ; Smith, Scott L. ; Tuma, Dean J. / Increased covalent binding of acetaldehyde to calmodulin in the presence of calcium. In: Life Sciences. 1989 ; Vol. 45, No. 16. pp. 1461-1466.
@article{1dc096ef6c134f6abaef6c741891b72c,
title = "Increased covalent binding of acetaldehyde to calmodulin in the presence of calcium",
abstract = "The regulatory protein, calmodulin, undergoes major conformational changes in response to changes in intracellular calcium concentration. Furthermore, calmodulin has been reported to have lysine residues which markedly increase their reactivity toward electrophilic substances in the calcium-loaded state. We found that calmodulin formed two or three times more stable adducts with acetaldehyde in the calcium-loaded state as compared to the calcium-free state. Competition-binding studies showed that calmodulin could preferentially compete with albumin for acetaldehyde in the presence, but not in the absence, of calcium. When calmodulin was in the calcium-loaded state, trifluoperazine, an inhibitor of calmodulin activity, significantly decreased the stable binding of acetaldehyde to the protein, whereas in the calcium-free state, minimal effects on binding were observed. Since calmodulin is involved in regulation of multiple important processes in the cell, it is possible that acetaldehyde-calmodulin adducts could contribute to liver injury by perturbation of calcium-dependent homeostatic mechanisms within the hepatocyte.",
author = "Jennett, {Richard B.} and Abbas Saffari-Fard and Sorrell, {Michael Floyd} and Smith, {Scott L.} and Tuma, {Dean J.}",
year = "1989",
doi = "10.1016/0024-3205(89)90036-2",
language = "English (US)",
volume = "45",
pages = "1461--1466",
journal = "Life Sciences",
issn = "0024-3205",
publisher = "Elsevier Inc.",
number = "16",

}

TY - JOUR

T1 - Increased covalent binding of acetaldehyde to calmodulin in the presence of calcium

AU - Jennett, Richard B.

AU - Saffari-Fard, Abbas

AU - Sorrell, Michael Floyd

AU - Smith, Scott L.

AU - Tuma, Dean J.

PY - 1989

Y1 - 1989

N2 - The regulatory protein, calmodulin, undergoes major conformational changes in response to changes in intracellular calcium concentration. Furthermore, calmodulin has been reported to have lysine residues which markedly increase their reactivity toward electrophilic substances in the calcium-loaded state. We found that calmodulin formed two or three times more stable adducts with acetaldehyde in the calcium-loaded state as compared to the calcium-free state. Competition-binding studies showed that calmodulin could preferentially compete with albumin for acetaldehyde in the presence, but not in the absence, of calcium. When calmodulin was in the calcium-loaded state, trifluoperazine, an inhibitor of calmodulin activity, significantly decreased the stable binding of acetaldehyde to the protein, whereas in the calcium-free state, minimal effects on binding were observed. Since calmodulin is involved in regulation of multiple important processes in the cell, it is possible that acetaldehyde-calmodulin adducts could contribute to liver injury by perturbation of calcium-dependent homeostatic mechanisms within the hepatocyte.

AB - The regulatory protein, calmodulin, undergoes major conformational changes in response to changes in intracellular calcium concentration. Furthermore, calmodulin has been reported to have lysine residues which markedly increase their reactivity toward electrophilic substances in the calcium-loaded state. We found that calmodulin formed two or three times more stable adducts with acetaldehyde in the calcium-loaded state as compared to the calcium-free state. Competition-binding studies showed that calmodulin could preferentially compete with albumin for acetaldehyde in the presence, but not in the absence, of calcium. When calmodulin was in the calcium-loaded state, trifluoperazine, an inhibitor of calmodulin activity, significantly decreased the stable binding of acetaldehyde to the protein, whereas in the calcium-free state, minimal effects on binding were observed. Since calmodulin is involved in regulation of multiple important processes in the cell, it is possible that acetaldehyde-calmodulin adducts could contribute to liver injury by perturbation of calcium-dependent homeostatic mechanisms within the hepatocyte.

UR - http://www.scopus.com/inward/record.url?scp=0024325903&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024325903&partnerID=8YFLogxK

U2 - 10.1016/0024-3205(89)90036-2

DO - 10.1016/0024-3205(89)90036-2

M3 - Article

C2 - 2509834

AN - SCOPUS:0024325903

VL - 45

SP - 1461

EP - 1466

JO - Life Sciences

JF - Life Sciences

SN - 0024-3205

IS - 16

ER -