Enhanced Delivery of Rapamycin by V156K-apoA-I High-Density Lipoprotein Inhibits Cellular Proatherogenic Effects and Senescence and Promotes Tissue Regeneration

Title
Enhanced Delivery of Rapamycin by V156K-apoA-I High-Density Lipoprotein Inhibits Cellular Proatherogenic Effects and Senescence and Promotes Tissue Regeneration
Author(s)
조경현
Keywords
APOLIPOPROTEIN-A-I; ESTER TRANSFER PROTEIN; LIPID TRANSFER PROTEINS; APOA-I; RECONSTITUTED HDL; THERAPY; V156K; OXIDATION; LONGEVITY; ATHEROSCLEROSIS
Issue Date
201112
Publisher
OXFORD UNIV PRESS INC
Citation
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES, v.66, no.12, pp.1274 - 1285
Abstract
Although rapamycin (rapa) is a fungicide, it is now believed to possess the capacity to extend mammalian life span. Because rapamycin is insoluble in water, its study in the aqueous phase has been limited. We therefore solubilized rapamycin in isotonic buffer using reconstituted high-density lipoprotein containing V156K-apolipoprotein A-I (V156K-rHDL). Rapamycin (final concentration, 0.1 mg/mL) was solubilized in rHDL containing either wild-type (WT) or V156K-apoA-I (1 mg/mL of protein) prepared using the sodium cholate dialysis method. V156K-rHDL containing rapamycin (V156K-rapa-rHDL) had a slightly larger particle size than rapamycin-loaded WT-rHDL (WT-rapa-rHDL). V156K-rapa-rHDL exhibited enhanced antioxidant ability, cholesteryl ester transfer protein inhibitory activity, and anti-atherosclerotic activity. Treatment with V156K-rapa-rHDL resulted in attenuation of senescence in human cells with increased cell survival and enhancement of tissue regenerative activities in zebrafish model compared with WT-rapa-rHDL or rHDL alone.
URI
http://hdl.handle.net/YU.REPOSITORY/24160http://dx.doi.org/10.1093/gerona/glr169
ISSN
1079-5006
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