PMID- 30027367
OWN - NLM
STAT- MEDLINE
DCOM- 20190722
LR  - 20190722
IS  - 1559-0720 (Electronic)
IS  - 0163-4984 (Linking)
VI  - 189
IP  - 1
DP  - 2019 May
TI  - Zinc Chelator Inhibits Zinc-Induced Islet Amyloid Polypeptide Deposition and 
      Apoptosis in INS-1 Cells.
PG  - 201-208
LID - 10.1007/s12011-018-1444-5 [doi]
AB  - Amyloid deposition and beta cell apoptosis are characteristic pathological 
      features of type 2 diabetes mellitus (DM). Islet amyloid polypeptide (IAPP) is 
      the most abundant component of amyloid deposition. Monomeric IAPP does not form 
      amyloid deposition, but the fibrous IAPP may aggregate and form amyloid deposits. 
      Previous studies have shown that zinc is closely related to IAPP deposition 
      through crosslink with monomeric IAPP into fibrous aggregates. In this study, we 
      aimed to investigate whether chelating zinc could inhibit zinc-induced amyloid 
      deposits and apoptosis of islet beta cell. N, N, N', N'-Tetrakis 
      (2-pyridylmethyl) ethylenediamine (TPEN) is a specific chelator of zinc, with 
      membrane permeability. It could effectively reduce the concentration of 
      intracellular zinc. So, we used TPEN to treat hIAPP-transfected INS-1 cells. By 
      MTT assay, the concentration (1 muM) and incubation time (12 h) of TPEN without 
      affecting cell viability were determined. The results showed that TPEN reduced 
      zinc-induced IAPP deposition in the culture system. Furthermore, we analyzed the 
      effect of zinc and TPEN on the apoptosis and insulin level. The results showed 
      that TPEN could reverse zinc-induced INS-1 cell apoptosis and insulin secretion. 
      And the anti-apoptosis effects of TPEN is related to extracellular regulated 
      protein kinases (ERK)/c-jun N-terminal kinase (JNK) signaling pathway. The 
      present data indicated that chelating zinc could inhibit zinc-induced amyloid 
      deposition and beta cell apoptosis. Thus, maintaining zinc homeostasis in islet 
      beta cell might become a useful strategy for DM therapy.
FAU - Tian, He
AU  - Tian H
AD  - Institute of Health Sciences, Key Laboratory of Medical Cell Biology of Ministry 
      of education, China Medical University, Shenyang, 110122, People's Republic of 
      China.
AD  - Department of Histology and Embryology, Jinzhou Medical University, Jinzhou, 
      121000, People's Republic of China.
FAU - Wang, Zhan-You
AU  - Wang ZY
AUID- ORCID: 0000-0003-0807-9916
AD  - Institute of Health Sciences, Key Laboratory of Medical Cell Biology of Ministry 
      of education, China Medical University, Shenyang, 110122, People's Republic of 
      China. wangzy@cmu.edu.cn.
LA  - eng
GR  - 2012CB722405/National Program on Key Basic Research Project (973 Program)/
PT  - Journal Article
DEP - 20180719
PL  - United States
TA  - Biol Trace Elem Res
JT  - Biological trace element research
JID - 7911509
RN  - 0 (Chelating Agents)
RN  - 0 (Islet Amyloid Polypeptide)
RN  - J41CSQ7QDS (Zinc)
SB  - IM
MH  - Apoptosis/drug effects
MH  - Blotting, Western
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - Chelating Agents/*pharmacology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Flow Cytometry
MH  - Fluorescent Antibody Technique
MH  - Humans
MH  - Islet Amyloid Polypeptide/*metabolism
MH  - Signal Transduction/drug effects
MH  - Zinc/*pharmacology
OTO - NOTNLM
OT  - Apoptosis
OT  - Diabetes mellitus
OT  - Islet amyloid polypeptide
OT  - Zinc
OT  - Zinc chelator
EDAT- 2018/07/22 06:00
MHDA- 2019/07/23 06:00
CRDT- 2018/07/21 06:00
PHST- 2018/04/04 00:00 [received]
PHST- 2018/07/12 00:00 [accepted]
PHST- 2018/07/22 06:00 [pubmed]
PHST- 2019/07/23 06:00 [medline]
PHST- 2018/07/21 06:00 [entrez]
AID - 10.1007/s12011-018-1444-5 [pii]
AID - 10.1007/s12011-018-1444-5 [doi]
PST - ppublish
SO  - Biol Trace Elem Res. 2019 May;189(1):201-208. doi: 10.1007/s12011-018-1444-5. 
      Epub 2018 Jul 19.