The enhancing effect of homocysteine thiolactone on insulin fibrillation and cytotoxicity of insulin fibril.
In the current study both structural alteration and fibrillation of insulin were studied in the presence of homocysteine thiolactone (HCTL). The spectroscopic studies revealed that HCTL increases rate of insulin unfolding, giving rise to the appearance of solvent-exposed hydrophobic regions and induces a transition from α-helix into predominantly β-sheet structures. Thioflavin-T fluorescence studies revealed that HCTL markedly enhanced the quantity of insulin fibril formation in both agitating and non-agitating systems. Also gel electrophoresis results suggest that HCTL accelerates the process of formation of high molecular weight insulin aggregates. Moreover, insulin fibrils obtained in the presence of HCTL and those collected earlier in the pathway of insulin fibrillation displayed improved cytotoxicity against cancer cells. The enhancement of insulin fibril formation with elevated cytotoxic properties as occurred in the presence of HCTL, may suggest this homocysteine derivative as a possible contributing factor in the pathology of insulin fibrils.
Protein Chemistry Laboratory, Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran. ryousefi@shirazu.ac.ir
Reza
R
Yousefi
Shima
S
Jalili
Parnian
P
Alavi
Ali-Akbar
AA
Moosavi-Movahedi
D000818:Animals; D002417:Cattle; D002460:Cell Line; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000737:chemistry; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007328:Insulin / Q000737:chemistry* / Q000633:toxicity; D046912:Multiprotein Complexes / Q000737:chemistry / Q000633:toxicity; D017434:Protein Structure, Tertiary
D007328:Insulin; D046912:Multiprotein Complexes; D006710:Homocysteine; C007957:homocysteine thiolactone