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Data of ureagenesis from ammonia, glutamine and alanine, and mitochondrial aquaporin-8 expression in thioacetamide-treated hepatocytes.

ABSTRACT: We present data about the synthesis of urea from different substrates, i.e., free ammonia, glutamine and alanine in primary cultured rat hepatocytes treated or untreated with the model hepatotoxic agent thioacetamide (TAA). We also provide data about the expression of mitochondrial aquaporin-8 (mtAQP8), a hepatocyte channel protein which facilitates ammonia diffusion into mitochondria to supply the urea cycle. Ammonia-derived ureagenesis was significantly inhibited by about 30% while that from the both amino acids resulted unaffected in TAA-treated hepatocytes. Protein expression of mtAQP8 was decreased by about 80% after TAA treatment. These data can be useful for the understanding of the mechanisms of drug-induced hepatic dysfunction.

SUBMITTER: Capiglioni AM

PROVIDER: S-EPMC7210421 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Data of ureagenesis from ammonia, glutamine and alanine, and mitochondrial aquaporin-8 expression in thioacetamide-treated hepatocytes.

Capiglioni Alejo M AM Alvarez María de Luján ML Marinelli Raúl A RA

Data in brief 20200430

We present data about the synthesis of urea from different substrates, i.e., free ammonia, glutamine and alanine in primary cultured rat hepatocytes treated or untreated with the model hepatotoxic agent thioacetamide (TAA). We also provide data about the expression of mitochondrial aquaporin-8 (mtAQP8), a hepatocyte channel protein which facilitates ammonia diffusion into mitochondria to supply the urea cycle. Ammonia-derived ureagenesis was significantly inhibited by about 30% while that from t ...[more]

PMID: 32395591

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Project description:Thioacetamide (TA) has long been known as a hepatotoxicant whose bioactivation requires S-oxidation to thioacetamide S-oxide (TASO) and then to the very reactive S,S-dioxide (TASO2). The latter can tautomerize to form acylating species capable of covalently modifying cellular nucleophiles including phosphatidylethanolamine (PE) lipids and protein lysine side chains. Isolated hepatocytes efficiently oxidize TA to TASO but experience little covalent binding or cytotoxicity because TA is a very potent inhibitor of the oxidation of TASO to TASO2. However, hepatocytes treated with TASO show extensive covalent binding to both lipids and proteins accompanied by extensive cytotoxicity. In this work, we treated rat hepatocytes with [(14)C]-TASO and submitted the mitochondrial, microsomal, and cytosolic fractions to 2DGE, which revealed a total of 321 radioactive protein spots. To facilitate the identification of target proteins and adducted peptides, we also treated cells with a mixture of TASO/[(13)C2D3]-TASO. Using a combination of 1DGE- and 2DGE-based proteomic approaches, we identified 187 modified peptides (174 acetylated, 50 acetimidoylated, and 37 in both forms) from a total of 88 nonredundant target proteins. Among the latter, 57 are also known targets of at least one other hepatotoxin. The formation of both amide- and amidine-type adducts to protein lysine side chains is in contrast to the exclusive formation of amidine-type adducts with PE phospholipids. Thiobenzamide (TB) undergoes the same two-step oxidative bioactivation as TA, and it also gives rise to both amide and amidine adducts on protein lysine side chains but only amidine adducts to PE lipids. Despite their similarity in functional group chemical reactivity, only 38 of 62 known TB target proteins are found among the 88 known targets of TASO. The potential roles of protein modification by TASO in triggering cytotoxicity are discussed in terms of enzyme inhibition, protein folding, and chaperone function, and the emerging role of protein acetylation in intracellular signaling and the regulation of biochemical pathways.

Dataset Information

Data of ureagenesis from ammonia, glutamine and alanine, and mitochondrial aquaporin-8 expression in thioacetamide-treated hepatocytes.

Publications

Data of ureagenesis from ammonia, glutamine and alanine, and mitochondrial aquaporin-8 expression in thioacetamide-treated hepatocytes.

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