| First Author | Liu Z | Year | 2020 |
| Journal | Biochim Biophys Acta Mol Basis Dis | Volume | 1866 |
| Issue | 3 | Pages | 165634 |
| PubMed ID | 31830527 | Mgi Jnum | J:283586 |
| Mgi Id | MGI:6387129 | Doi | 10.1016/j.bbadis.2019.165634 |
| Citation | Liu Z, et al. (2020) Betaine/GABA transporter-1 (BGT-1) deficiency in mouse prevents acute liver failure in vivo and hepatocytes apoptosis in vitro. Biochim Biophys Acta Mol Basis Dis 1866(3):165634 |
| abstractText | Betaine/gamma-aminobutyric acid (GABA) transporter 1 (BGT-1 or Slc6a12) is a transporter for the neurotransmitter GABA and osmolyte betaine. To date, most studies on BGT-1 have focused on its functions in the nervous system and renal osmotic homeostasis. Despite its dominant distribution in the liver, the function of BGT-1 in hepatic physiology or disease remains unknown. Here, we report that BGT-1 was significantly downregulated in patients with liver failure as well as in mice with experimental acute liver failure (ALF). Furthermore, mice deficient in BGT-1 showed significant resistance to ALF compared with wild type (WT) mice, manifesting as improved survival rate, reduced alanine transaminase/aspartate aminotransferase levels, better histopathological symptoms and fewer apoptotic cells in the liver. Similarly, in primary hepatocytes, BGT-1 deficiency or treatment with a BGT-1 inhibitor, NNC 05-2090, attenuated TNF-alpha mediated apoptosis. In addition, BGT-1 deficiency or dosing with NNC 05-2090 stimulated the expression of the anti-apoptotic gene, c-Met in the liver, suggesting the involvement of c-Met in the function on hepatocytes of BGT-1 apoptosis. Our findings suggest BGT-1 is a promising candidate drug target to prevent and treat hepatocyte apoptosis related diseases, such as ALF. |
