{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zhang C"],"funding":["Taishan Pandeng Scholar Program of Shandong Province","National Key R&amp;D Program of China","National Key R&D Program of China","the State Key Program of the National Natural Science Foundation of China","Natural Science Foundation of Shandong Province","National Natural Science Foundation of China","Clinical Research Foundation of Shandong University"],"pagination":["59"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11281981"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["40(1)"],"pubmed_abstract":["Acute liver injury (ALI) is a common life-threatening condition with a high mortality rate due to liver disease-related death. However, current therapeutic interventions for ALI remain ineffective, and the development of effective novel therapies is urgently needed. Liver samples from patients with drug-induced ALI were collected to detect adenosine kinase (ADK) expression. Male C57BL/6 J mice, hepatocyte-specific ADK knockout (ADK<sup>HKO</sup>) mice, and their controls (ADK<sup>f/f</sup>) were exposed to acetaminophen (APAP) and other treatments to investigate the mechanisms of APAP-related ALI. ADK expression was significantly decreased in APAP-injured livers. Hepatocyte-specific ADK deficiency exacerbated APAP-induced ALI, while a gain-of-function approach delivering AAV-ADK, markedly alleviated APAP-induced ALI, as indicated by changes in alanine aminotransferases (ALT) levels, aspartate aminotransferase (AST) levels, neutrophil infiltration and hepatocyte death. This study showed that ADK played a critical role in ALI by activating autophagy through two signaling pathways, the adenosine monophosphate-activated protein kinase (AMPK)-mTOR pathway and the adenosine receptor A1 (ADORA1)-Akt-mTOR pathway. Furthermore, we found that metformin upregulated ADK expression in hepatocytes and protected against APAP-induced ALI. These results demonstrate that ADK is critical in protecting against APAP-induced ALI and that developing therapeutics targeting ADK-adenosine-ADORA1 is a new approach for ALI treatment. Metformin is a potential candidate for preventing ALI by upregulating ADK."],"journal":["Cell biology and toxicology"],"pubmed_title":["Adenosine kinase protects against acetaminophen-induced acute liver injury by activating autophagy in hepatocytes."],"pmcid":["PMC11281981"],"funding_grant_id":["tspd20181220","82030059","2020YFC1512700","2020SDUCRCC014","ZR2022QH225","82072141"],"pubmed_authors":["Liu X","Liu H","Wang B","Yuan Q","Wei S","Ma J","Wang G","Chen Y","Hua R","Zhang C","Zou D"],"additional_accession":[]},"is_claimable":false,"name":"Adenosine kinase protects against acetaminophen-induced acute liver injury by activating autophagy in hepatocytes.","description":"Acute liver injury (ALI) is a common life-threatening condition with a high mortality rate due to liver disease-related death. However, current therapeutic interventions for ALI remain ineffective, and the development of effective novel therapies is urgently needed. Liver samples from patients with drug-induced ALI were collected to detect adenosine kinase (ADK) expression. Male C57BL/6 J mice, hepatocyte-specific ADK knockout (ADK<sup>HKO</sup>) mice, and their controls (ADK<sup>f/f</sup>) were exposed to acetaminophen (APAP) and other treatments to investigate the mechanisms of APAP-related ALI. ADK expression was significantly decreased in APAP-injured livers. Hepatocyte-specific ADK deficiency exacerbated APAP-induced ALI, while a gain-of-function approach delivering AAV-ADK, markedly alleviated APAP-induced ALI, as indicated by changes in alanine aminotransferases (ALT) levels, aspartate aminotransferase (AST) levels, neutrophil infiltration and hepatocyte death. This study showed that ADK played a critical role in ALI by activating autophagy through two signaling pathways, the adenosine monophosphate-activated protein kinase (AMPK)-mTOR pathway and the adenosine receptor A1 (ADORA1)-Akt-mTOR pathway. Furthermore, we found that metformin upregulated ADK expression in hepatocytes and protected against APAP-induced ALI. These results demonstrate that ADK is critical in protecting against APAP-induced ALI and that developing therapeutics targeting ADK-adenosine-ADORA1 is a new approach for ALI treatment. Metformin is a potential candidate for preventing ALI by upregulating ADK.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jul","modification":"2025-04-04T13:41:49.185Z","creation":"2025-04-04T13:41:49.185Z"},"accession":"S-EPMC11281981","cross_references":{"pubmed":["39060559"],"doi":["10.1007/s10565-024-09906-0"]}}