Effects of dithiothreitol on the amyloid fibrillogenesis of hen egg-white lysozyme.
At least 25 human proteins can fold abnormally to form pathological deposits that are associated with several degenerative diseases. Despite extensive investigation on amyloid fibrillation, the detailed molecular mechanisms remain rather elusive and there are currently no effective cures for treating these amyloid diseases. The present study examined the effects of dithiothreitol on the fibrillation of hen egg-white lysozyme (HEWL). Our results revealed that the fibrillation of hen lysozyme was significantly inhibited by reduced dithiothreitol (DTT(red)) while oxidized dithiothreitol (DTT(ox)) had no anti-aggregating activity. Effective inhibitory activity against hen lysozyme fibrillation was observed only when DTT(red) was added within 8 days of incubation. Our results showed that the initial addition of DTT(red) interacted with HEWL, leading to a loss in conformational stability. It was concluded from our findings that DTT(red)-induced attenuation of HEWL fibrillation may be associated with disulfide disruption and extensive structural unfolding of HEWL. Our data may contribute to rational design of effective therapeutic strategies for amyloid diseases.
Wang
Steven S-S
SS
Department of Chemical Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei, 10617, Taiwan. sswang@ntu.edu.tw
Liu
Kuan-Nan
KN
Wang
Bo-Wei
BW
D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D030161:Avian Proteins / Q000378:metabolism*; D002491:Central Nervous System Agents / Q000737:chemistry / Q000494:pharmacology*; D002645:Chickens; D004229:Dithiothreitol / Q000737:chemistry / Q000494:pharmacology*; D004527:Egg Proteins / Q000378:metabolism*; D004529:Egg White; D005260:Female; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D009113:Muramidase / Q000378:metabolism*; D010084:Oxidation-Reduction; D011487:Protein Conformation / Q000187:drug effects; D017510:Protein Folding / Q000187:drug effects; D055503:Protein Multimerization / Q000187:drug effects*; D055550:Protein Stability / Q000187:drug effects; D013816:Thermodynamics; D014508:Urea / Q000378:metabolism
D000682:Amyloid; D030161:Avian Proteins; D002491:Central Nervous System Agents; D004527:Egg Proteins; D014508:Urea; D009113:Muramidase; D004229:Dithiothreitol