Journal
CELLULAR SIGNALLING
Volume 91, Issue -, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2021.110222
Keywords
Adiponectin; Apolipoprotein A-I; ATP binding cassette transporter A1; Carboxy-terminal domain; Cholesterol efflux; Binding
Categories
Funding
- Canadian Institutes of Health Research (CIHR) [PJT-148966]
- Heart & Stroke Foundation of Canada [G-17-0018755]
- Postdoctoral Fellowships from the Research Institute of the McGill University Health Centre
- CIHR [RN408399 - 430975]
- Societe quebecoise d'hypertension arterielle scholarship
- NIH NHLBI [RO1 HL138907]
- Fonds de recherche du Quebec-Sante-Senior salary award
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The study found that adiponectin plays a protective role in cholesterol efflux, but the involvement of apoA-I residues in this process has not been studied. This study used macrophages and cell models to show that adiponectin requires specific residues of apoA-I and wild-type ABCA1 to restore cholesterol efflux. Adiponectin cannot rescue defective cholesterol efflux in apoA-I or ABCA1 mutant conditions, but it increases cholesterol efflux compared to apoA-I exposure alone in wild-type apoA-I conditions.
Adiponectin exerts its atheroprotection by stimulating adenosine triphosphate binding cassette transporter A1 (ABCA1)-mediated cholesterol efflux to apolipoprotein A-I (apoA-I). However, involvement of the apoA-I resi-dues in this process have not been studied. In Tamm-Horsfall 1 (THP-1) macrophages and baby hamster kidney (BHK) cells we assessed adiponectin's potential to restore cholesterol efflux in the presence of apoA-I and ABCA1 mutants, respectively. Adiponectin was unable to restore efflux from THP-1 macrophages in the presence of apoA-I carboxy-terminal domain (CTD) successive mutants from residues 187-243 versus apoA-I mutants alone. Furthermore, adiponectin did not significantly influence cholesterol efflux to apoA-I from BHK-ABCA1 mutant cells. Adiponectin appears to require functional apoA-I CTD residues 187-243 and wild-type ABCA1 to mediate efficient cholesterol efflux from THP-1 macrophages and BHK cells, respectively. Therefore, adiponectin cannot rescue defective cholesterol efflux in apoA-I-or ABCA1-mutant conditions, but rather increases cholesterol efflux in wild-type apoA-I conditions compared to apoA-I exposure alone.
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