Amyloid fibrillation and cytotoxicity of insulin are inhibited by the amphiphilic surfactants.
Amyloid fibrils have been associated with at least 25 different degenerative diseases. The 51-residue polypeptide hormone insulin, which is associated with type II diabetes, has been shown to self-assemble to form amyloid fibrils in vitro. With bovine insulin as a model, the research presented here explores the effects of two amphiphilic surfactants (1,2-dihexanoyl-sn-glycero-3-phosphocholine (di-C7-PC) and 1,2-diheptanoyl-sn-glycero-3-phosphocholine (di-C7-PC)) on the in vitro fibrillation process of bovine insulin at pH 2.0 and 55 degrees C. We demonstrated that insulin fibrillation may be inhibited by both surfactants in a dose-dependent fashion. The best inhibition of fibril formation is observed when insulin is incubated with 4mM di-C7-PC. Moreover, the addition of either surfactant at the concentrations studied attenuated insulin fibril-induced cytotoxicity in both PC12 and SH-SY5Y cell lines. The results from this work may contribute to the understanding of the molecular factors affecting amyloid fibrillation and the molecular mechanism(s) of the interactions between the membrane and amyloid proteins.
Wang
Steven S-S
SS
Department of Chemical Engineering, National Taiwan University, Taipei 10617, Taiwan. sswang@ntu.edu.tw
Liu
Kuan-Nan
KN
Han
Tzu-Chiang
TC
D000682:Amyloid / Q000096:biosynthesis* / Q000737:chemistry / Q000648:ultrastructure; D000686:Amyloidosis / Q000188:drug therapy; D000818:Animals; D002417:Cattle; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity*; D046529:Microscopy, Electron, Transmission; D008954:Models, Biological; D016716:PC12 Cells; D010713:Phosphatidylcholines / Q000494:pharmacology; D010742:Phospholipid Ethers / Q000494:pharmacology; D055503:Protein Multimerization / Q000187:drug effects; D017433:Protein Structure, Secondary / Q000187:drug effects; D051381:Rats; D013501:Surface-Active Agents / Q000494:pharmacology*
C052298:1,2-dihexadecyl-sn-glycero-3-phosphocholine; C092445:1,2-dihexanoyl-sn-glycero-3-phosphorylcholine; D000682:Amyloid; D007328:Insulin; D010713:Phosphatidylcholines; D010742:Phospholipid Ethers; D013501:Surface-Active Agents