Bisphenol A accelerates toxic amyloid formation of human islet amyloid polypeptide: a possible link between bisphenol A exposure and type 2 diabetes.
Bisphenol A (BPA) is a chemical compound widely used in manufacturing plastic products. Recent epidemiological studies suggest BPA exposure is positively associated with the incidence of type 2 diabetes mellitus (T2DM), however the mechanisms underlying this link remain unclear. Human islet amyloid polypeptide (hIAPP) is a hormone synthesized and secreted by the pancreatic β-cells. Misfolding of hIAPP into toxic oligomers and mature fibrils can disrupt cell membrane and lead to β-cell death, which is regarded as one of the causative factors of T2DM. To test whether there are any connections between BPA exposure and hIAPP misfolding, we investigated the effects of BPA on hIAPP aggregation using thioflavin-T based fluorescence, transmission electronic microscopy, circular dichroism, dynamic light scattering, size-exclusion chromatography, fluorescence-dye leakage assay in an artificial micelle system and the generation of reactive oxygen species in INS-1 cells. We demonstrated that BPA not only dose-dependently promotes the aggregation of hIAPP and enhances the membrane disruption effects of hIAPP, but also promotes the extent of hIAPP aggregation related oxidative stress. Taken together, our results suggest that BPA exposure increased T2DM risk may involve the exacerbated toxic aggregation of hIAPP.
Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
Hao
H
Gong
Xin
X
Zhang
Biao
B
Cheng
Yue
Y
Sun
Chuanzhou
C
Li
Ting
T
Li
Ling
L
Zheng
Kun
K
Huang
D000395:Air Pollutants, Occupational / Q000633:toxicity*; D000595:Amino Acid Sequence; D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity*; D052160:Benzothiazoles; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects; D002942:Circular Dichroism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D058228:Islet Amyloid Polypeptide / Q000032:analysis* / Q000138:chemical synthesis / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D058977:Molecular Sequence Annotation; D018384:Oxidative Stress; D010636:Phenols / Q000633:toxicity*; D017510:Protein Folding / Q000187:drug effects; D017433:Protein Structure, Secondary; D051381:Rats; D013844:Thiazoles; D000098826:Bisphenol A Compounds
D000395:Air Pollutants, Occupational; D001559:Benzhydryl Compounds; D052160:Benzothiazoles; D058228:Islet Amyloid Polypeptide; D010636:Phenols; D013844:Thiazoles; C009462:thioflavin T; C006780:bisphenol A; D000098826:Bisphenol A Compounds