Caveolin-1 attenuates acetaminophen aggravated lipid accumulation in alcoholic fatty liver by activating mitophagy via the Pink-1/Parkin pathway.
Eur J Pharmacol
; 908: 174324, 2021 Oct 05.
Article
en En
| MEDLINE
| ID: mdl-34246650
ABSTRACT
Alcoholic fatty liver (AFL) is a disease characterized by the abnormal structure and dysfunction of hepatocytes caused by long-term, excessive drinking. Acetaminophen (APAP) is a commonly used painkiller, but it can aggravate lipid deposition in the liver and cause liver injury when used in fatty liver disease. Here, we investigated the effect of caveolin-1 (CAV-1), an intracellular stent protein, on the pathogenesis of APAP aggravated lipid deposition in AFL mice. This study shows that lipid accumulation was more severe in APAP groups than in alcohol-treated mice. The CAV-1 stent-like domain (CSD, 82-101 amino acids of caveolin-1), used to upregulate CAV-1 expression, could reduce lipid accumulation and activate autophagy in AFL mice treated with APAP. The levels of CAV-1 and autophagy-related proteins (LC3-II/I and Beclin-1) had decreased, whereas SREBP-1c had increased in A/O (alcohol and oleic acid) and APAP-co-treated L02 cells. CAV-1 small interfering RNA and CAV1-overexpressing plasmid were separately transfected into A/O and APAP co-treated L02 cells. When CAV-1 was downregulated, the levels of Pink-1, Parkin, and autophagy-related proteins (LC3-II/I and Beclin-1) were decreased, whereas SREBP-1c was increased. The opposite trend was observed when CAV-1 was overexpressed. The results show that CAV-1 reduced lipid accumulation in L02 cells and activated Pink-1/Parkin-related mitophagy. This study highlights the positive role of CAV-1 in APAP-increased lipid accumulation under the AFL status and provides a new understanding of the function of CAV-1 in the liver through mitophagy associated with the Pink-1/Parkin pathway.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Mitofagia
/
Acetaminofén
Límite:
Animals
Idioma:
En
Revista:
Eur J Pharmacol
Año:
2021
Tipo del documento:
Article