Pub. Date : 2020 Nov 1
PMID : 32738395
7 Functional Relationships(s)Download |
Sentence | Compound Name | Protein Name | Organism |
| 1 | Alcohol-induced CYP2E1, Mitochondrial Dynamics and Retrograde Signaling in Human Hepatic 3D Organoids. | Alcohols | cytochrome P450 family 2 subfamily E member 1 | Homo sapiens |
| 2 | Alcohol is metabolized to the toxic metabolite, acetaldehyde by alcohol dehydrogenase or CYP2E1 in the hepatic tissue, and also induces reactive oxygen species (ROS), which together play a pivotal role in cell and tissue damage. | Alcohols | cytochrome P450 family 2 subfamily E member 1 | Homo sapiens |
| 3 | Our previous studies with COS-7 cells transduced with unique human CYP2E1 variants that mostly localize to either microsomes or mitochondria revealed that mitochondrially-localized CYP2E1 drives alcohol toxicity through the generation of higher levels of ROS, which has a consequent effect on cytochrome c oxidase (CcO) and mitochondrial oxidative function. | Alcohols | cytochrome P450 family 2 subfamily E member 1 | Homo sapiens |
| 4 | Our previous studies with COS-7 cells transduced with unique human CYP2E1 variants that mostly localize to either microsomes or mitochondria revealed that mitochondrially-localized CYP2E1 drives alcohol toxicity through the generation of higher levels of ROS, which has a consequent effect on cytochrome c oxidase (CcO) and mitochondrial oxidative function. | Alcohols | cytochrome P450 family 2 subfamily E member 1 | Homo sapiens |
| 5 | Alcohol treatment of 3D organoids of HepaRG cells induced higher levels of CYP2E1 mRNA and activated mitochondrial stress-induced retrograde signaling, and also induced markers of hepatic steatosis. | Alcohols | cytochrome P450 family 2 subfamily E member 1 | Homo sapiens |
| 6 | Knock down of CYP2E1 mRNA using specific shRNA, FK506, a Calcineurin inhibitor, and Mdivi-1, a DRP1 inhibitor, ameliorated alcohol-induced mitochondrial retrograde signaling, and hepatic steatosis. | Alcohols | cytochrome P450 family 2 subfamily E member 1 | Homo sapiens |
| 7 | These results for the first time present a mechanistic link between CYP2E1 function and alcohol mediated mitochondrial dysfunction, retrograde signaling, and activation of hepatic steatosis in a 3D organoid system that closely recapitulates the in vivo liver response. | Alcohols | cytochrome P450 family 2 subfamily E member 1 | Homo sapiens |