Clusterin: full-length protein and one of its chains show opposing effects on cellular lipid accumulation
| Autor: | Chintalagiri Mohan Rao, Ramakrishna Tangirala, Suvarsha Rao Matukumalli |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Time Factors Weight Gain Article law.invention Cell Line 03 medical and health sciences Mice law In vivo medicine Animals Humans Cell Shape Cellular localization Multidisciplinary Clusterin biology Chemistry Lipid metabolism Metabolism medicine.disease Lipid Metabolism eye diseases Cell biology 030104 developmental biology Biochemistry Cell culture Recombinant DNA biology.protein sense organs Rabbits Steatosis Molecular Chaperones Subcellular Fractions |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep41235 |
| Popis: | Proteins, made up of either single or multiple chains, are designed to carry out specific biological functions. We found an interesting example of a two-chain protein where administration of one of its chains leads to a diametrically opposite outcome than that reported for the full-length protein. Clusterin is a highly glycosylated protein consisting of two chains, α- and β-clusterin. We have investigated the conformational features, cellular localization, lipid accumulation, in vivo effects and histological changes upon administration of recombinant individual chains of clusterin. We demonstrate that recombinant α- and β-chains exhibit structural and functional differences and differ in their sub-cellular localization. Full-length clusterin is known to lower lipid levels. In contrast, we find that β-chain-treated cells accumulate 2-fold more lipid than controls. Interestingly, α-chain-treated cells do not show such increase. Rabbits injected with β-chain, but not α-chain, show ~40% increase in weight, with adipocyte hypertrophy, liver and kidney steatosis. Many, sometimes contrasting, roles are ascribed to clusterin in obesity, metabolic syndrome and related conditions. Our findings of differential localization and activities of individual chains of clusterin should help in understanding better the roles of clusterin in metabolism. |
| Databáze: | OpenAIRE |
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