Project: Research project

Project Details


Sera from patients with halothane hepatitis contain antibodies directed
against liver microsomal proteins (100 kDa, 80 kDa, 63 kDa, 59 kDa, 58 kDa,
57 kDa, and 54 kDa) covalently modified by the trifluoroacetyl halide
metabolite of halothane. These altered proteins (neoantigens) are believed
to cause an immune-mediated hepatotoxicity. In this project, the 80 kDa
protein was purified from liver microsomes of halothane treated and
untreated rats by ionic exchange chromatography. An antibody was raised
against the protein in rabbits and was used to determine the subcellular
localization and organ distribution of the protein. Quantitative
immunoblotting studies revealed that the highest levels of the protein were
found in the microsomal fraction of the liver, followed by approximately
50% lower amounts in the nuclear, mitochondrial, and plasma membrane
fractions. Very low levels of the protein were detected in the cytosol
fraction of the liver. The protein was detected in all tissues studied with
the highest levels found in the liver, fat, and testes, while moderate
levels were measured in all other tissues tested except for the heart and
skeletal muscle which had low levels of the protein. When the amino acid
sequences of several internal peptides produced by either tryptic or mild
acid hydrolysis of the protein were compared to sequences of proteins in
several data bases, it was discovered that the 80 kDa protein showed
greater than 95% sequence homology with two cDNA clones. One of the clones
encoded for ERp 72, an endoplasmic reticulum protein with unknown function.
The other clone corresponded to deoxycytidine kinase, the rate-limiting
enzyme in the activation of many important anticancer and retroviral drugs,
including the anti-AIDS drug AZT.
Effective start/end date9/15/013/31/08


  • National Institutes of Health: $126,900.00
  • National Institutes of Health: $126,900.00
  • National Institutes of Health: $126,900.00
  • National Institutes of Health: $126,900.00
  • National Institutes of Health: $126,900.00


  • Medicine(all)


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