PMID- 18190941
OWN - NLM
STAT- MEDLINE
DCOM- 20080505
LR  - 20161124
IS  - 0041-008X (Print)
IS  - 0041-008X (Linking)
VI  - 227
IP  - 3
DP  - 2008 Mar 15
TI  - Orai1-STIM1 formed store-operated Ca2+ channels (SOCs) as the molecular 
      components needed for Pb2+ entry in living cells.
PG  - 430-9
LID - 10.1016/j.taap.2007.11.025 [doi]
AB  - Heavy metal lead (Pb2+) is a pollutant and causes severe toxicity when present in 
      human tissues especially the nervous system. Recent reviews have suggested that 
      Pb2+ can target Ca2+-related proteins within neurons and that Ca2+ channels might 
      be a candidate for Pb2+ entry. This study's main aim was to identify the 
      functional entry pathway of Pb2+ into living cells. We firstly characterized the 
      endogenous expression of Orai1 and STIM1 mRNA together with the level of 
      thapsigargin (TG) stimulated capacitative Ca2+ entry in PC12 and HeLa cells; this 
      was done by RT-PCR and time-lapse Ca2+ imaging microscopy, respectively. Our data 
      supported Orai1 and STIM1 as contributing to store-operated Ca2+ channel (SOC) 
      basal activity. Secondly, using the indo-1 quenching method with the SOC blocker 
      2-APB, we observed that Pb2+ was able to enter cells directly through unactivated 
      SOCs without TG pretreatment. Thirdly, we further demonstrated that co-expression 
      of Orai1 and STIM1 differentially enhanced SOC functional activity (4-fold with 
      PC12 and 5-fold with HeLa cells) and Pb2+ entry (5- to 7-fold with PC12 and 
      2-fold with HeLa cells). Furthermore, after a 1 h of Pb2+ exposure, the 
      depolarization- and histamine-induced Ca2+ responses were significantly decreased 
      in both PC12 and HeLa cells in a dose-dependent manner. This result indicated 
      that the decreased Ca2+ responses were, in part, due to Pb2+ entry. In summary, 
      our results suggest that SOCs are responsible for Pb2+ permeation and that the 
      Orai1-STIM1 protein complex formed by functional SOCs is one of the molecular 
      components involved in Pb2+ entry.
FAU - Chang, Yu-Fen
AU  - Chang YF
AD  - Department of Medical Research and Education, Taipei Veterans General Hospital, 
      Taiwan, Republic of China.
FAU - Teng, Hsiao-Chuan
AU  - Teng HC
FAU - Cheng, Sha-Yen
AU  - Cheng SY
FAU - Wang, Chin-Tien
AU  - Wang CT
FAU - Chiou, Shi-Hwa
AU  - Chiou SH
FAU - Kao, Lung-Sen
AU  - Kao LS
FAU - Kao, Fu-Jen
AU  - Kao FJ
FAU - Chiou, Arthur
AU  - Chiou A
FAU - Yang, De-Ming
AU  - Yang DM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071204
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Boron Compounds)
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Calcium Channels)
RN  - 0 (Cations, Divalent)
RN  - 0 (Membrane Proteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (ORAI1 Protein)
RN  - 0 (ORAI1 protein, human)
RN  - 0 (STIM1 protein, human)
RN  - 0 (Stromal Interaction Molecule 1)
RN  - 2P299V784P (Lead)
RN  - E4ES684O93 (2-aminoethoxydiphenyl borate)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Biological Transport
MH  - Boron Compounds/pharmacology
MH  - Calcium/metabolism
MH  - Calcium Channel Blockers/pharmacology
MH  - Calcium Channels/analysis/drug effects/*metabolism
MH  - Cations, Divalent/metabolism
MH  - HeLa Cells
MH  - Humans
MH  - Lead/*metabolism
MH  - Membrane Proteins/analysis/*metabolism
MH  - Neoplasm Proteins/analysis/*metabolism
MH  - ORAI1 Protein
MH  - PC12 Cells
MH  - Rats
MH  - Stromal Interaction Molecule 1
EDAT- 2008/01/15 09:00
MHDA- 2008/05/06 09:00
CRDT- 2008/01/15 09:00
PHST- 2007/08/27 00:00 [received]
PHST- 2007/11/15 00:00 [revised]
PHST- 2007/11/16 00:00 [accepted]
PHST- 2008/01/15 09:00 [pubmed]
PHST- 2008/05/06 09:00 [medline]
PHST- 2008/01/15 09:00 [entrez]
AID - S0041-008X(07)00519-4 [pii]
AID - 10.1016/j.taap.2007.11.025 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2008 Mar 15;227(3):430-9. doi: 
      10.1016/j.taap.2007.11.025. Epub 2007 Dec 4.