RGD Reference Report - Alanine aminotransferase isoenzymes: molecular cloning and quantitative analysis of tissue expression in rats and serum elevation in liver toxicity. - Rat Genome Database

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Alanine aminotransferase isoenzymes: molecular cloning and quantitative analysis of tissue expression in rats and serum elevation in liver toxicity.

Authors: Yang, Rong-Ze  Park, Soohyun  Reagan, William J  Goldstein, Rick  Zhong, Shao  Lawton, Michael  Rajamohan, Francis  Qian, Kun  Liu, Li  Gong, Da-Wei 
Citation: Yang RZ, etal., Hepatology. 2009 Feb;49(2):598-607. doi: 10.1002/hep.22657.
RGD ID: 14975249
Pubmed: PMID:19085960   (View Abstract at PubMed)
PMCID: PMC2917112   (View Article at PubMed Central)
DOI: DOI:10.1002/hep.22657   (Journal Full-text)


UNLABELLED: The elevation of serum alanine aminotransferase (ALT) is regarded as an indicator of liver damage based on the presumption that ALT protein is specifically and abundantly expressed in the liver. However, ALT elevation is also observed in non-liver injury conditions (for example, muscle injury) and in apparently healthy people. Conversely, serum ALT activity is normal in many patients with confirmed liver diseases (for example, cirrhosis and hepatitis C infection). To improve the diagnostic value of the ALT assay and to understand the molecular basis for serum ALT changes in various pathophysiological conditions, we have cloned rat ALT isoenzyme ALT1 and ALT2 complementary DNAs (cDNAs), examined their tissue expressions at the messenger RNA and protein levels, and determined ALT1 and ALT 2 serum levels in response to liver damage in rodents. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis shows that ALT1 messenger RNA is widely distributed and mainly expressed in intestine, liver, fat tissues, colon, muscle, and heart, in the order of high to low expression level, whereas ALT2 gene expression is more restricted, mainly in liver, muscle, brain, and white adipose tissue. The tissue distribution pattern of ALT1 and ALT2 proteins largely agrees with their messenger RNA expression. Interestingly, hepatic ALT2 protein is approximately four times higher in male rats than in female rats. In addition, ALT isoenzymes distribute differentially at the subcellular level in that ALT1 is a cytoplasmic protein and ALT2 a mitochondrial protein, supporting bioinformatic prediction of mitochondrial localization of ALT2.
CONCLUSION: Using animal models of hepatoxicity induced by carbon tetrachloride and acetaminophen, we found that both serum ALT1 and ALT2 protein levels were significantly elevated and correlated with ALT activity, providing, for the first time, the molecular basis for the elevated total serum ALT activity.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Chemical and Drug Induced Liver Injury  ISOGpt (Rattus norvegicus)14975249; 14975249protein:increased expression and activity:serum:RGD 
Chemical and Drug Induced Liver Injury  ISOGpt (Mus musculus)14975249; 14975249protein:increased expression and activity:serum:RGD 
Chemical and Drug Induced Liver Injury  ISOGpt2 (Rattus norvegicus)14975249; 14975249protein:increased expression and activity:serum:RGD 
Chemical and Drug Induced Liver Injury  ISOGpt2 (Mus musculus)14975249; 14975249protein:increased expression and activity:serum:RGD 
Chemical and Drug Induced Liver Injury  IEP 14975249; 14975249; 14975249; 14975249protein:increased expression and activity:serum:RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
extracellular space  IDA 14975249; 14975249MMO:0000075RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gpt  (glutamic--pyruvic transaminase)
Gpt2  (glutamic--pyruvic transaminase 2)

Genes (Mus musculus)
Gpt  (glutamic pyruvic transaminase, soluble)
Gpt2  (glutamic pyruvate transaminase (alanine aminotransferase) 2)

Genes (Homo sapiens)
GPT  (glutamic--pyruvic transaminase)
GPT2  (glutamic--pyruvic transaminase 2)


Additional Information