Isoaspartate, carbamoyl phosphate synthase-1, and carbonic anhydrase-III as biomarkers of liver injury

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Isoaspartate, carbamoyl phosphate synthase-1, and carbonic anhydrase-III as biomarkers of liver injury. / Carter, Wayne G; Vigneswara, Vasanthy; Newlaczyl, Anna; Wayne, Declan; Ahmed, Bilal ; Saddington, Stephen; Brewer, Charlotte; Raut, Nikhilesh; Gerdes, Henry K; Erdozain, Amaia M; Tooth, David; Bolt, Edward L; Osna, Natalie A; Tuma, Dean J; Kharbanda, Kusum K.

In: Biochemical and Biophysical Research Communications, Vol. 458, No. 3, 13.03.2015, p. 626-31.

Research output: Contribution to journalArticlepeer-review

Harvard

Carter, WG, Vigneswara, V, Newlaczyl, A, Wayne, D, Ahmed, B, Saddington, S, Brewer, C, Raut, N, Gerdes, HK, Erdozain, AM, Tooth, D, Bolt, EL, Osna, NA, Tuma, DJ & Kharbanda, KK 2015, 'Isoaspartate, carbamoyl phosphate synthase-1, and carbonic anhydrase-III as biomarkers of liver injury', Biochemical and Biophysical Research Communications, vol. 458, no. 3, pp. 626-31. https://doi.org/10.1016/j.bbrc.2015.01.158

APA

Carter, W. G., Vigneswara, V., Newlaczyl, A., Wayne, D., Ahmed, B., Saddington, S., Brewer, C., Raut, N., Gerdes, H. K., Erdozain, A. M., Tooth, D., Bolt, E. L., Osna, N. A., Tuma, D. J., & Kharbanda, K. K. (2015). Isoaspartate, carbamoyl phosphate synthase-1, and carbonic anhydrase-III as biomarkers of liver injury. Biochemical and Biophysical Research Communications, 458(3), 626-31. https://doi.org/10.1016/j.bbrc.2015.01.158

Vancouver

Author

Carter, Wayne G ; Vigneswara, Vasanthy ; Newlaczyl, Anna ; Wayne, Declan ; Ahmed, Bilal ; Saddington, Stephen ; Brewer, Charlotte ; Raut, Nikhilesh ; Gerdes, Henry K ; Erdozain, Amaia M ; Tooth, David ; Bolt, Edward L ; Osna, Natalie A ; Tuma, Dean J ; Kharbanda, Kusum K. / Isoaspartate, carbamoyl phosphate synthase-1, and carbonic anhydrase-III as biomarkers of liver injury. In: Biochemical and Biophysical Research Communications. 2015 ; Vol. 458, No. 3. pp. 626-31.

Bibtex

@article{db7014024d3a44279c68a1f8be451ad1,
title = "Isoaspartate, carbamoyl phosphate synthase-1, and carbonic anhydrase-III as biomarkers of liver injury",
abstract = "We had previously shown that alcohol consumption can induce cellular isoaspartate protein damage via an impairment of the activity of protein isoaspartyl methyltransferase (PIMT), an enzyme that triggers repair of isoaspartate protein damage. To further investigate the mechanism of isoaspartate accumulation, hepatocytes cultured from control or 4-week ethanol-fed rats were incubated in vitro with tubercidin or adenosine. Both these agents, known to elevate intracellular S-adenosylhomocysteine levels, increased cellular isoaspartate damage over that recorded following ethanol consumption in vivo. Increased isoaspartate damage was attenuated by treatment with betaine. To characterize isoaspartate-damaged proteins that accumulate after ethanol administration, rat liver cytosolic proteins were methylated using exogenous PIMT and 3H-S-adenosylmethionine and proteins resolved by gel electrophoresis. Three major protein bands of ∼75-80 kDa, ∼95-100 kDa, and ∼155-160 kDa were identified by autoradiography. Column chromatography used to enrich isoaspartate-damaged proteins indicated that damaged proteins from ethanol-fed rats were similar to those that accrued in the livers of PIMT knockout (KO) mice. Carbamoyl phosphate synthase-1 (CPS-1) was partially purified and identified as the ∼160 kDa protein target of PIMT in ethanol-fed rats and in PIMT KO mice. Analysis of the liver proteome of 4-week ethanol-fed rats and PIMT KO mice demonstrated elevated cytosolic CPS-1 and betaine homocysteine S-methyltransferase-1 when compared to their respective controls, and a significant reduction of carbonic anhydrase-III (CA-III) evident only in ethanol-fed rats. Ethanol feeding of rats for 8 weeks resulted in a larger (∼2.3-fold) increase in CPS-1 levels compared to 4-week ethanol feeding indicating that CPS-1 accumulation correlated with the duration of ethanol consumption. Collectively, our results suggest that elevated isoaspartate and CPS-1, and reduced CA-III levels could serve as biomarkers of hepatocellular injury.",
keywords = "Animals, Biomarkers, Carbamoyl-Phosphate Synthase (Ammonia), Carbonic Anhydrase-III, Cells, Cultured, Drug-Induced Liver Injury, Ethanol, Isoaspartic Acid, Liver, Male, Mice, Mice, Knockout, Protein D-Aspartate-L-Isoaspartate Methyltransferase, Rats, Rats, Wistar, S-Adenosylhomocysteine, Alcohol-induced liver injury, Carbamoyl phosphate synthase-1, Isoaspartate, Liver proteome, Protein isoaspartyl, methyltransferase",
author = "Carter, {Wayne G} and Vasanthy Vigneswara and Anna Newlaczyl and Declan Wayne and Bilal Ahmed and Stephen Saddington and Charlotte Brewer and Nikhilesh Raut and Gerdes, {Henry K} and Erdozain, {Amaia M} and David Tooth and Bolt, {Edward L} and Osna, {Natalie A} and Tuma, {Dean J} and Kharbanda, {Kusum K}",
note = "Copyright {\textcopyright} 2015 The Authors. Published by Elsevier Inc. All rights reserved.",
year = "2015",
month = mar,
day = "13",
doi = "10.1016/j.bbrc.2015.01.158",
language = "English",
volume = "458",
pages = "626--31",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Elsevier",
number = "3",

}

RIS

TY - JOUR

T1 - Isoaspartate, carbamoyl phosphate synthase-1, and carbonic anhydrase-III as biomarkers of liver injury

AU - Carter, Wayne G

AU - Vigneswara, Vasanthy

AU - Newlaczyl, Anna

AU - Wayne, Declan

AU - Ahmed, Bilal

AU - Saddington, Stephen

AU - Brewer, Charlotte

AU - Raut, Nikhilesh

AU - Gerdes, Henry K

AU - Erdozain, Amaia M

AU - Tooth, David

AU - Bolt, Edward L

AU - Osna, Natalie A

AU - Tuma, Dean J

AU - Kharbanda, Kusum K

N1 - Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2015/3/13

Y1 - 2015/3/13

N2 - We had previously shown that alcohol consumption can induce cellular isoaspartate protein damage via an impairment of the activity of protein isoaspartyl methyltransferase (PIMT), an enzyme that triggers repair of isoaspartate protein damage. To further investigate the mechanism of isoaspartate accumulation, hepatocytes cultured from control or 4-week ethanol-fed rats were incubated in vitro with tubercidin or adenosine. Both these agents, known to elevate intracellular S-adenosylhomocysteine levels, increased cellular isoaspartate damage over that recorded following ethanol consumption in vivo. Increased isoaspartate damage was attenuated by treatment with betaine. To characterize isoaspartate-damaged proteins that accumulate after ethanol administration, rat liver cytosolic proteins were methylated using exogenous PIMT and 3H-S-adenosylmethionine and proteins resolved by gel electrophoresis. Three major protein bands of ∼75-80 kDa, ∼95-100 kDa, and ∼155-160 kDa were identified by autoradiography. Column chromatography used to enrich isoaspartate-damaged proteins indicated that damaged proteins from ethanol-fed rats were similar to those that accrued in the livers of PIMT knockout (KO) mice. Carbamoyl phosphate synthase-1 (CPS-1) was partially purified and identified as the ∼160 kDa protein target of PIMT in ethanol-fed rats and in PIMT KO mice. Analysis of the liver proteome of 4-week ethanol-fed rats and PIMT KO mice demonstrated elevated cytosolic CPS-1 and betaine homocysteine S-methyltransferase-1 when compared to their respective controls, and a significant reduction of carbonic anhydrase-III (CA-III) evident only in ethanol-fed rats. Ethanol feeding of rats for 8 weeks resulted in a larger (∼2.3-fold) increase in CPS-1 levels compared to 4-week ethanol feeding indicating that CPS-1 accumulation correlated with the duration of ethanol consumption. Collectively, our results suggest that elevated isoaspartate and CPS-1, and reduced CA-III levels could serve as biomarkers of hepatocellular injury.

AB - We had previously shown that alcohol consumption can induce cellular isoaspartate protein damage via an impairment of the activity of protein isoaspartyl methyltransferase (PIMT), an enzyme that triggers repair of isoaspartate protein damage. To further investigate the mechanism of isoaspartate accumulation, hepatocytes cultured from control or 4-week ethanol-fed rats were incubated in vitro with tubercidin or adenosine. Both these agents, known to elevate intracellular S-adenosylhomocysteine levels, increased cellular isoaspartate damage over that recorded following ethanol consumption in vivo. Increased isoaspartate damage was attenuated by treatment with betaine. To characterize isoaspartate-damaged proteins that accumulate after ethanol administration, rat liver cytosolic proteins were methylated using exogenous PIMT and 3H-S-adenosylmethionine and proteins resolved by gel electrophoresis. Three major protein bands of ∼75-80 kDa, ∼95-100 kDa, and ∼155-160 kDa were identified by autoradiography. Column chromatography used to enrich isoaspartate-damaged proteins indicated that damaged proteins from ethanol-fed rats were similar to those that accrued in the livers of PIMT knockout (KO) mice. Carbamoyl phosphate synthase-1 (CPS-1) was partially purified and identified as the ∼160 kDa protein target of PIMT in ethanol-fed rats and in PIMT KO mice. Analysis of the liver proteome of 4-week ethanol-fed rats and PIMT KO mice demonstrated elevated cytosolic CPS-1 and betaine homocysteine S-methyltransferase-1 when compared to their respective controls, and a significant reduction of carbonic anhydrase-III (CA-III) evident only in ethanol-fed rats. Ethanol feeding of rats for 8 weeks resulted in a larger (∼2.3-fold) increase in CPS-1 levels compared to 4-week ethanol feeding indicating that CPS-1 accumulation correlated with the duration of ethanol consumption. Collectively, our results suggest that elevated isoaspartate and CPS-1, and reduced CA-III levels could serve as biomarkers of hepatocellular injury.

KW - Animals

KW - Biomarkers

KW - Carbamoyl-Phosphate Synthase (Ammonia)

KW - Carbonic Anhydrase-III

KW - Cells, Cultured

KW - Drug-Induced Liver Injury

KW - Ethanol

KW - Isoaspartic Acid

KW - Liver

KW - Male

KW - Mice

KW - Mice, Knockout

KW - Protein D-Aspartate-L-Isoaspartate Methyltransferase

KW - Rats

KW - Rats, Wistar

KW - S-Adenosylhomocysteine

KW - Alcohol-induced liver injury

KW - Carbamoyl phosphate synthase-1

KW - Isoaspartate

KW - Liver proteome

KW - Protein isoaspartyl

KW - methyltransferase

U2 - 10.1016/j.bbrc.2015.01.158

DO - 10.1016/j.bbrc.2015.01.158

M3 - Article

C2 - 25684186

VL - 458

SP - 626

EP - 631

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 3

ER -