The amyloid aggregation of hIAPP and the increased level of oxidative stress are closely related to the occurrence and development of type 2 diabetes (T2D). Protein tyrosine nitration is a common post-translational modification under oxidative stress conditions. We previously found that tyrosine nitrated hIAPP (3-NT-hIAPP) has higher cytotoxicity than wild type hIAPP. In order to further elucidate the mechanism by which tyrosine nitration enhances the toxicity of hIAPP, we systematically studied the effect of tyrosine nitration on hIAPP aggregation and its impact on INS-1 cells. Collective experimental data from ThT, RLS, DLS, zeta potentials, Bis-ANS, H NMR, TEM, dye leakage and hemolysis confirmed that tyrosine nitration accelerates hIAPP aggregation, consistent with tyrosine nitration reducing hIAPP zeta potential, but 3-NT-hIAPP mainly undergoes an off-pathway aggregation to form amorphous aggregates, even in the presence of POPC/POPG LUVs. Further, our results confirmed that the most toxic species are the small amorphous aggregates formed by 3-NT-hIAPP, which is more stable and toxic than hIAPP oligomers. Collectively, these data suggest that tyrosine nitration can increase cytotoxicity of hIAPP by modulating its amyloidogenicity. This study provides new support for the fact that oxidative stress promotes the development of T2D from the view of nitrative stress.
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http://dx.doi.org/10.1016/j.ijbiomac.2024.138367 | DOI Listing |
Int J Biol Macromol
December 2024
Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, School of Chemistry and Chemical Engineering, Huazhong University of Science & Technology, Wuhan, 430074, PR China. Electronic address:
The amyloid aggregation of hIAPP and the increased level of oxidative stress are closely related to the occurrence and development of type 2 diabetes (T2D). Protein tyrosine nitration is a common post-translational modification under oxidative stress conditions. We previously found that tyrosine nitrated hIAPP (3-NT-hIAPP) has higher cytotoxicity than wild type hIAPP.
View Article and Find Full Text PDFFree Radic Biol Med
December 2024
Dept. of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address:
Redox Rep
December 2024
Department of Emergency Medicine, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, People's Republic of China.
Cardiol Res
October 2024
Sarajevo Medical School, University Sarajevo School of Science and Technology, Sarajevo, Bosnia and Hercegovina.
Chronic coronary syndrome (CCS) is a long-term manifestation of coronary artery disease, marked by stable but recurring chest pain and myocardial ischemia due to the gradual buildup of atherosclerotic plaques in the coronary arteries. It is a metabolic disorder of coronary arteries characterized by oxidative stress, endothelial dysfunction, inflammation, and hyperlipidemia. The imbalance in oxidative-antioxidative status contributes to stable ischemic heart disease.
View Article and Find Full Text PDFNitric Oxide
December 2024
The Laboratory of Emergency Medicine, School of Second Clinical Medicine, Xuzhou Medical University, Xuzhou, Jiangsu, 221002, China; Department of Emergency Medicine, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221002, China. Electronic address:
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