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Nitration of hIAPP promotes its toxic oligomer formation and exacerbates its toxicity towards INS-1 cells.
Zhao, Jie; Wu, Jinming; Yang, Zhen; Ouyang, Lei; Zhu, Lihua; Gao, Zhonghong; Li, Hailing.
Afiliação
  • Zhao J; Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan, 430074, People's Republic of China.
  • Wu J; Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan, 430074, People's Republic of China.
  • Yang Z; Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan, 430074, People's Republic of China; Center for Bioenergetics, Houston Methodist Research Institute, Houston, TX, 77030, United Stat
  • Ouyang L; Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan, 430074, People's Republic of China.
  • Zhu L; Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan, 430074, People's Republic of China.
  • Gao Z; Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan, 430074, People's Republic of China. Electronic address: zhgao144@mail.hust.edu.cn.
  • Li H; Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan, 430074, People's Republic of China. Electronic address: lihailing86@hust.edu.cn.
Nitric Oxide ; 87: 23-30, 2019 06 01.
Article em En | MEDLINE | ID: mdl-30849493
Amyloid formation of human islet amyloid polypeptide (hIAPP) is one of the most common pathological features of type 2 diabetes (T2D). Increasing evidences have shown that the overproduction of reactive oxygen species (ROS) and reactive nitrogen species (RNS) play an important role in the development of the T2D. Interestingly, our previous studies indicated that heme could bind to hIAPP, and the complex might induce the nitration of tyrosine residue (Y37) of hIAPP in the presence of hydrogen peroxide and nitrite. However, it remains unclear about effect of the nitration on the implicated function of hIAPP in the development of T2D. In this study, fluorescent assays, transmission electron microscopy (TEM), atomic force microscope (AFM) were used to demonstrate that nitration of hIAPP significantly decreased its fibril formation. But the decreased fibril formation was not through the diminished aggregation of hIAPP monomer as suggested by the results of circular dichroism spectroscopy (CD) and gel electrophoresis assay. Surface-enhanced raman spectroscopy (SERS) indicated that nitration of hIAPP impaired the intermolecular hydrogen bonding. On the basis of these results, we hypothesize that nitration of hIAPP may block the intermolecular hydrogen bonding, leading to the inhibition of its fibril formation. In addition, cytotoxicity study of native and modified hIAPP was also performed on INS-1 cells, which revealed exacerbated toxicity of hIAPP by its nitration. The findings in this study that nitration of hIAPP promotes its oligomer formation and thus exacerbates its cytotoxicity suggests a possible link between the nitrite (or the sum of nitrite and nitrate) levels and T2D, and ameliorated nitration of hIAPP by diminishing nitrative stress might be a promising therapeutic strategy for T2D.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Processamento de Proteína Pós-Traducional / Polipeptídeo Amiloide das Ilhotas Pancreáticas Limite: Animals Idioma: En Revista: Nitric Oxide Assunto da revista: BIOQUIMICA / QUIMICA Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Processamento de Proteína Pós-Traducional / Polipeptídeo Amiloide das Ilhotas Pancreáticas Limite: Animals Idioma: En Revista: Nitric Oxide Assunto da revista: BIOQUIMICA / QUIMICA Ano de publicação: 2019 Tipo de documento: Article