PMID- 28787568
OWN - NLM
STAT- MEDLINE
DCOM- 20170928
LR  - 20180127
IS  - 1520-5010 (Electronic)
IS  - 0893-228X (Linking)
VI  - 30
IP  - 9
DP  - 2017 Sep 18
TI  - Strong Inhibitory Effect of Heme on hIAPP Fibrillation.
PG  - 1711-1719
LID - 10.1021/acs.chemrestox.7b00170 [doi]
AB  - The deposition of human islet amyloid polypeptide (hIAPP) within beta-cells is 
      implicated in the etiology of type 2 diabetes mellitus (T2Dm). It was reported 
      that heme could bind to hIAPP. We speculate that binding may affect the 
      aggregation of hIAPP. In this study, UV-vis spectroscopy was used to detect the 
      interaction pattern between the heme and hIAPP. ThT and Bis-ANS fluorescence 
      assay, circular dichroism spectroscopy, gel electrophoresis assay, and 
      transmission electron microscopy were employed to study the effect of heme on the 
      aggregation of hIAPP. We found that heme dramatically inhibited hIAPP 
      aggregation, even partially dismantled hIAPP aggregates by preventing its 
      conformational changes. Moreover, a similar inhibitory effect was also observed 
      on mutant hIAPP. In the compared group, the inhibitory effects of protoporphyrin 
      on hIAPP and its mutants aggregation were weaker. Similarly, its effect on the 
      dismantlement of the aggregates was also weaker. On the basis of these results, 
      we revealed that the heme iron center was not required for the inhibitory effect 
      on hIAPP but affected the binding affinity of heme to hIAPP. Besides Arg11 and 
      His18, other hydrophobic residues of hIAPP may also play important roles in heme 
      binding. Our results may help to develop an in-depth understanding of the 
      interaction between heme and hIAPP, which would be helpful in designing new 
      therapeutic strategies against T2Dm.
FAU - Wu, Jinming
AU  - Wu J
AD  - School of Chemistry and Chemical Engineering, Huazhong University of Science and 
      Technology , Wuhan 430074, People's Republic of China.
FAU - Zhao, Jie
AU  - Zhao J
AD  - School of Chemistry and Chemical Engineering, Huazhong University of Science and 
      Technology , Wuhan 430074, People's Republic of China.
FAU - Yang, Zhen
AU  - Yang Z
AD  - School of Chemistry and Chemical Engineering, Huazhong University of Science and 
      Technology , Wuhan 430074, People's Republic of China.
AD  - Department of Chemical and Biomolecular Engineering, University of Houston , 
      Houston, Texas 77004, United States.
FAU - Li, Hailing
AU  - Li H
AD  - School of Chemistry and Chemical Engineering, Huazhong University of Science and 
      Technology , Wuhan 430074, People's Republic of China.
AD  - Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, Huazhong 
      University of Science and Technology , 1037 Luoyu Road, Wuhan 430074, People's 
      Republic of China.
FAU - Gao, Zhonghong
AU  - Gao Z
AUID- ORCID: 0000-0002-7878-9801
AD  - School of Chemistry and Chemical Engineering, Huazhong University of Science and 
      Technology , Wuhan 430074, People's Republic of China.
AD  - Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, Huazhong 
      University of Science and Technology , 1037 Luoyu Road, Wuhan 430074, People's 
      Republic of China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170823
PL  - United States
TA  - Chem Res Toxicol
JT  - Chemical research in toxicology
JID - 8807448
RN  - 0 (Islet Amyloid Polypeptide)
RN  - 0 (Protoporphyrins)
RN  - 42VZT0U6YR (Heme)
RN  - C2K325S808 (protoporphyrin IX)
SB  - IM
MH  - Circular Dichroism
MH  - Electrophoresis, Gel, Pulsed-Field
MH  - Heme/*chemistry/metabolism
MH  - Humans
MH  - Islet Amyloid Polypeptide/*chemistry/metabolism
MH  - Microscopy, Electron, Transmission
MH  - Protein Binding
MH  - Protoporphyrins/chemistry
MH  - Spectrometry, Fluorescence
EDAT- 2017/08/09 06:00
MHDA- 2017/09/29 06:00
CRDT- 2017/08/09 06:00
PHST- 2017/08/09 06:00 [pubmed]
PHST- 2017/09/29 06:00 [medline]
PHST- 2017/08/09 06:00 [entrez]
AID - 10.1021/acs.chemrestox.7b00170 [doi]
PST - ppublish
SO  - Chem Res Toxicol. 2017 Sep 18;30(9):1711-1719. doi: 
      10.1021/acs.chemrestox.7b00170. Epub 2017 Aug 23.