Protein Glycation by Glyoxal Promotes Amyloid Formation by Islet Amyloid Polypeptide

Yi Hsuan Hsu, Yun Wen Chen, Meng Hsin Wu, Ling Hsien Tu*


研究成果: 雜誌貢獻期刊論文同行評審

10 引文 斯高帕斯(Scopus)


Protein glycation, also known as nonenzymatic glycosylation, is a spontaneous post-translational modification that would change the structure and stability of proteins or hormone peptides. Recent studies have indicated that glycation plays a role in type 2 diabetes (T2D) and neurodegenerative diseases. Over the last two decades, many types of advanced glycation end products (AGEs), formed through the reactions of an amino group of proteins with reducing sugars, have been identified and detected in vivo. However, the effect of glycation on protein aggregation has not been fully investigated. In this study, we aim to elucidate the impact of protein glycation on islet amyloid polypeptide (IAPP, also known as amylin) aggregation, which was strongly associated with T2D. We chemically synthesized glycated IAPP (AGE-IAPP) to mimic the consequence of this hormone peptide in a hyperglycemia (high blood sugar) environment. Our data revealed that AGE-IAPP formed amyloid faster than normal IAPP, and higher-molecular-weight AGE-IAPP oligomers were also observed in the early stage of aggregation. Circular dichroism spectra also indicated that AGE-IAPP exhibited faster conformational changes from random coil to its β-sheet fibrillar states. Moreover, AGE-IAPP can induce normal IAPP to expedite its aggregation process, and its fibrils can also act as templates to promote IAPP aggregation. AGE-IAPP, like normal IAPP, is capable of interacting with synthetic membranes and also exhibits cytotoxicity. Our studies demonstrated that glycation modification of IAPP promotes the amyloidogenic properties of IAPP, and it may play a role in accumulating additional amyloid during T2D progression.

頁(從 - 到)2304-2313
期刊Biophysical Journal
出版狀態已發佈 - 2019 六月 18

ASJC Scopus subject areas

  • 生物物理學


深入研究「Protein Glycation by Glyoxal Promotes Amyloid Formation by Islet Amyloid Polypeptide」主題。共同形成了獨特的指紋。