Research Article Details
| Article ID: | A27408 |
| PMID: | 18452708 |
| Source: | Biochem Biophys Res Commun |
| Title: | Free fatty acids sensitize hepatocytes to bile acid-induced apoptosis. |
| Abstract: | Delivery of free fatty acids to the liver in nonalcoholic fatty liver disease (NAFLD) may render hepatocytes more vulnerable to glycochenodeoxycholic acid (GCDCA)-induced apoptosis. Fat overloading was induced in HepG2-Ntcp cells and primary rat hepatocytes by incubation with palmitic or oleic acid. Apoptosis was quantified by measuring caspase 3/7 activity and transcription of interleukin (IL) 8 and IL-22 by quantitative real-time PCR. Oleic acid (500 microM) alone did not induce apoptosis, while palmitic acid (500 microM) increased apoptosis 5-fold. GCDCA did not induce significant apoptosis at low micromolar concentrations (5-30 microM) in non-steatotic cells. However, at the same concentrations, GCDCA increased apoptosis 3-fold in oleic acid-pretreated HepG2-Ntcp cells and 3.5-fold in primary rat hepatocytes. Pretreatment with oleic acid increased GCDCA-induced gene transcription of the proinflammatory cytokines IL-8 and IL-22 5-fold and 19-fold, respectively. Thus, low levels of cholestasis normally not considered harmful could advance liver injury in patients with NAFLD. |
| DOI: | 10.1016/j.bbrc.2008.04.113 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S13 | Anti-apoptosis | hepatocyte apoptosis; hepatic autophagy; apoptosis | Pan-caspase inhibitor | Emricasan | Details |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class |
|---|
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D316 | S-adenosyl-L-methionine | Chemical drug | DB00118 | GNMT cofactor | Antiviral | Under clinical trials | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |