Accumulation of proteins bearing atypical isoaspartyl residues in livers of alcohol-fed rats is prevented by betaine administration: Effects on protein-l-isoaspartyl methyltransferase activity

Kusum Kharbanda, Mark E Mailliard, Cheryl R. Baldwin, Michael Floyd Sorrell, Dean J. Tuma

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29 Citations (Scopus)

Abstract

Background/Aims: Protein-l-isoaspartyl methyltransferase (PIMT) is a methyltransferase that plays a crucial role in the repair of damaged proteins. In this study, we investigated whether ethanol exposure causes an accumulation of modified proteins bearing atypical isoaspartyl residues that may be related to impaired PIMT activity. We further sought to determine whether betaine administration could prevent the accumulation of these types of damaged proteins. Methods: Livers of male Wistar rats, fed the Lieber DeCarli control, ethanol or 1% betaine-supplemented diets for 4 weeks, were processed for PIMT-related analyses. Results: We observed a significant increase in the accumulation of modified proteins bearing isoaspartyl residues, i.e. the substrates for PIMT, in homogenate samples and various subcellular fractions of livers from ethanol-fed rats. Betaine supplementation prevented this accumulation of damaged proteins. In contrast, ethanol exposure induced no changes in the PIMT enzyme activity levels as compared to controls. The accumulation of damaged proteins negatively correlated with hepatic S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH) ratios. Conclusions: Ethanol consumption results in the accumulation of modified proteins bearing atypical isoaspartyl residues via impaired in vivo PIMT activity. Betaine administration prevents the ethanol-induced accumulation of isoaspartyl-containing proteins by restoring the PIMT-catalyzed protein repair reaction through normalizing the hepatocellular SAM:SAH ratios.

Original languageEnglish (US)
Pages (from-to)1119-1125
Number of pages7
JournalJournal of Hepatology
Volume46
Issue number6
DOIs
StatePublished - Jun 1 2007

Fingerprint

Betaine
Methyltransferases
Alcohols
Liver
Proteins
Ethanol
S-Adenosylhomocysteine
S-Adenosylmethionine
Protein Methyltransferases
Subcellular Fractions

Keywords

  • Alcohol
  • Betaine
  • Isoaspartyl residues
  • Liver
  • Methylation
  • Protein damage
  • Protein-l-isoaspartyl methyltransferase
  • S-Adenosylhomocysteine
  • S-Adenosylmethionine

ASJC Scopus subject areas

  • Hepatology

Cite this

@article{d6615bf054844cb9ba72e8b2ac1473b1,
title = "Accumulation of proteins bearing atypical isoaspartyl residues in livers of alcohol-fed rats is prevented by betaine administration: Effects on protein-l-isoaspartyl methyltransferase activity",
abstract = "Background/Aims: Protein-l-isoaspartyl methyltransferase (PIMT) is a methyltransferase that plays a crucial role in the repair of damaged proteins. In this study, we investigated whether ethanol exposure causes an accumulation of modified proteins bearing atypical isoaspartyl residues that may be related to impaired PIMT activity. We further sought to determine whether betaine administration could prevent the accumulation of these types of damaged proteins. Methods: Livers of male Wistar rats, fed the Lieber DeCarli control, ethanol or 1{\%} betaine-supplemented diets for 4 weeks, were processed for PIMT-related analyses. Results: We observed a significant increase in the accumulation of modified proteins bearing isoaspartyl residues, i.e. the substrates for PIMT, in homogenate samples and various subcellular fractions of livers from ethanol-fed rats. Betaine supplementation prevented this accumulation of damaged proteins. In contrast, ethanol exposure induced no changes in the PIMT enzyme activity levels as compared to controls. The accumulation of damaged proteins negatively correlated with hepatic S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH) ratios. Conclusions: Ethanol consumption results in the accumulation of modified proteins bearing atypical isoaspartyl residues via impaired in vivo PIMT activity. Betaine administration prevents the ethanol-induced accumulation of isoaspartyl-containing proteins by restoring the PIMT-catalyzed protein repair reaction through normalizing the hepatocellular SAM:SAH ratios.",
keywords = "Alcohol, Betaine, Isoaspartyl residues, Liver, Methylation, Protein damage, Protein-l-isoaspartyl methyltransferase, S-Adenosylhomocysteine, S-Adenosylmethionine",
author = "Kusum Kharbanda and Mailliard, {Mark E} and Baldwin, {Cheryl R.} and Sorrell, {Michael Floyd} and Tuma, {Dean J.}",
year = "2007",
month = "6",
day = "1",
doi = "10.1016/j.jhep.2007.01.026",
language = "English (US)",
volume = "46",
pages = "1119--1125",
journal = "Journal of Hepatology",
issn = "0168-8278",
publisher = "Elsevier",
number = "6",

}

TY - JOUR

T1 - Accumulation of proteins bearing atypical isoaspartyl residues in livers of alcohol-fed rats is prevented by betaine administration

T2 - Effects on protein-l-isoaspartyl methyltransferase activity

AU - Kharbanda, Kusum

AU - Mailliard, Mark E

AU - Baldwin, Cheryl R.

AU - Sorrell, Michael Floyd

AU - Tuma, Dean J.

PY - 2007/6/1

Y1 - 2007/6/1

N2 - Background/Aims: Protein-l-isoaspartyl methyltransferase (PIMT) is a methyltransferase that plays a crucial role in the repair of damaged proteins. In this study, we investigated whether ethanol exposure causes an accumulation of modified proteins bearing atypical isoaspartyl residues that may be related to impaired PIMT activity. We further sought to determine whether betaine administration could prevent the accumulation of these types of damaged proteins. Methods: Livers of male Wistar rats, fed the Lieber DeCarli control, ethanol or 1% betaine-supplemented diets for 4 weeks, were processed for PIMT-related analyses. Results: We observed a significant increase in the accumulation of modified proteins bearing isoaspartyl residues, i.e. the substrates for PIMT, in homogenate samples and various subcellular fractions of livers from ethanol-fed rats. Betaine supplementation prevented this accumulation of damaged proteins. In contrast, ethanol exposure induced no changes in the PIMT enzyme activity levels as compared to controls. The accumulation of damaged proteins negatively correlated with hepatic S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH) ratios. Conclusions: Ethanol consumption results in the accumulation of modified proteins bearing atypical isoaspartyl residues via impaired in vivo PIMT activity. Betaine administration prevents the ethanol-induced accumulation of isoaspartyl-containing proteins by restoring the PIMT-catalyzed protein repair reaction through normalizing the hepatocellular SAM:SAH ratios.

AB - Background/Aims: Protein-l-isoaspartyl methyltransferase (PIMT) is a methyltransferase that plays a crucial role in the repair of damaged proteins. In this study, we investigated whether ethanol exposure causes an accumulation of modified proteins bearing atypical isoaspartyl residues that may be related to impaired PIMT activity. We further sought to determine whether betaine administration could prevent the accumulation of these types of damaged proteins. Methods: Livers of male Wistar rats, fed the Lieber DeCarli control, ethanol or 1% betaine-supplemented diets for 4 weeks, were processed for PIMT-related analyses. Results: We observed a significant increase in the accumulation of modified proteins bearing isoaspartyl residues, i.e. the substrates for PIMT, in homogenate samples and various subcellular fractions of livers from ethanol-fed rats. Betaine supplementation prevented this accumulation of damaged proteins. In contrast, ethanol exposure induced no changes in the PIMT enzyme activity levels as compared to controls. The accumulation of damaged proteins negatively correlated with hepatic S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH) ratios. Conclusions: Ethanol consumption results in the accumulation of modified proteins bearing atypical isoaspartyl residues via impaired in vivo PIMT activity. Betaine administration prevents the ethanol-induced accumulation of isoaspartyl-containing proteins by restoring the PIMT-catalyzed protein repair reaction through normalizing the hepatocellular SAM:SAH ratios.

KW - Alcohol

KW - Betaine

KW - Isoaspartyl residues

KW - Liver

KW - Methylation

KW - Protein damage

KW - Protein-l-isoaspartyl methyltransferase

KW - S-Adenosylhomocysteine

KW - S-Adenosylmethionine

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U2 - 10.1016/j.jhep.2007.01.026

DO - 10.1016/j.jhep.2007.01.026

M3 - Article

C2 - 17336420

AN - SCOPUS:34247558033

VL - 46

SP - 1119

EP - 1125

JO - Journal of Hepatology

JF - Journal of Hepatology

SN - 0168-8278

IS - 6

ER -