Albumin fibrillization induces apoptosis via integrin/FAK/Akt pathway.

BMC Biotechnology
Chun-Yung HuangShu-Mei Liang

Abstract

Numerous proteins can be converted to amyloid-like fibrils to increase cytotoxicity and induce apoptosis, but the methods generally require a high concentration of protein, vigorous shaking, or fibril seed. As well, the detailed mechanism of the cytotoxic effects is not well characterized. In this study, we have developed a novel process to convert native proteins into the fibrillar form. We used globular bovine serum albumin (BSA) as a model protein to verify the properties of the fibrillar protein, investigated its cellular effects and studied the signaling cascade induced by the fibrillar protein. We induced BSA, a non-cytotoxic globular protein, to become fibril by a novel process involving Superdex-200 column chromatography in the presence of anionic or zwittergenic detergent(s). The column pore size was more important than column matrix composite in fibril formation. The fibrillar BSA induced apoptosis in BHK-21 cell as well as breast cancer cell line T47D. Pre-treating cells with anti-integrin antibodies blocked the apoptotic effect. Fibrillar BSA, but not globular BSA, bound to integrin, dephosphorylated focal adhesion kinase (FAK), Akt and glycogen synthase kinase-3beta (GSK-3beta). We report on a novel process for con...Continue Reading

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Citations

Apr 24, 2010·Apoptosis : an International Journal on Programmed Cell Death·Chun-Yung HuangShu-Mei Liang
Feb 9, 2010·Nature Reviews. Neurology·Agneta NordbergBengt Långström
Jul 8, 2011·Journal of Molecular Cell Biology·Yanying LiuRongqiao He
Oct 2, 2012·Pediatric Emergency Care·Marjorie L WhiteNancy M Tofil
Mar 16, 2012·Steroids·Kati E ShearerRoss V Weatherman
Aug 6, 2010·The Journal of Physical Chemistry. B·Nitin K PandeySwagata Dasgupta

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Methods Mentioned

BETA
gel filtration
transmission electron microscopy
gel-filtration
sizing
immunoprecipitation
column chromatography
ELISA
Protein Assay

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