Enhanced ammonia detoxification to urea in hepatocytes transduced with human aquaporin‐8 gene

ALEJO M. CAPIGLIONI; GABRIELA L. MÜLLER; JULIETA MARRONE; MARIA L. ALVAREZ; RAÚL A. MARINELLI

Biotechnology and Bioengineering

Wiley Periodicals, LLC.

Año: 2021

1097-0290

Hepatic ammonia detoxification to urea is critical for the prevention of hyperammonemiaand neurological damage. Hepatocyte mitochondrial aquaporin‐8(AQP8) channels have been involved in ammonia‐derived ureagenesis. Herein, westudied whether the adenoviral gene transfer of human AQP8 (hAQP8) to hepatocytemitochondria enhances ammonia conversion to urea. Using primary cultured rathepatocytes, we first confirmed the mitochondrial expression of hAQP8 and then,using unlabeled or 15N‐labeled ammonia, we demonstrated that the urea synthesiswas significantly enhanced in hAQP8‐transduced hepatocytes. Studies using isolatedhAQP8‐expressing mitochondria also showed an increased ammonia metabolism.hAQP8 transduction was able to recover the impaired ammonia‐derived ureagenesisin hepatotoxin‐treated hepatocytes. Our data suggest that mitochondriallyexpressedhAQP8 enhances and improves hepatocyte ammonia conversion to urea,a finding with potential therapeutic implications for liver disease with impairedammonia detoxification.