Enhanced ammonia detoxification to urea in hepatocytes transduced with human aquaporin‐8 gene
| Autor: | Julieta Marrone, Gabriela Leticia Müller, Raúl A. Marinelli, María de Luján Alvarez, Alejo M. Capiglioni |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Chemistry
Aquaporin Bioengineering Hyperammonemia Metabolism Mitochondrion Aquaporins medicine.disease Applied Microbiology and Biotechnology Rats Transduction (genetics) Ammonia chemistry.chemical_compound medicine.anatomical_structure Biochemistry Transduction Genetic Hepatocyte Hepatocytes medicine Urea Animals Humans Biotechnology |
| Zdroj: | Biotechnology and Bioengineering. 118:4331-4337 |
| ISSN: | 1097-0290 0006-3592 |
| DOI: | 10.1002/bit.27901 |
| Popis: | Hepatic ammonia detoxification to urea is critical for the prevention of hyperammonemia and neurological damage. Hepatocyte mitochondrial aquaporin-8 (AQP8) channels have been involved in ammonia-derived ureagenesis. Herein, we studied whether the adenoviral gene transfer of human AQP8 (hAQP8) to hepatocyte mitochondria enhances ammonia conversion to urea. Using primary cultured rat hepatocytes, we first confirmed the mitochondrial expression of hAQP8 and then, using unlabeled or 15 N-labeled ammonia, we demonstrated that the urea synthesis was significantly enhanced in hAQP8-transduced hepatocytes. Studies using isolated hAQP8-expressing mitochondria also showed an increased ammonia metabolism. hAQP8 transduction was able to recover the impaired ammonia-derived ureagenesis in hepatotoxin-treated hepatocytes. Our data suggest that mitochondrially-expressed hAQP8 enhances and improves hepatocyte ammonia conversion to urea, a finding with potential therapeutic implications for liver disease with impaired ammonia detoxification. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text