PMID- 18636168
OWN - NLM
STAT- MEDLINE
DCOM- 20080918
LR  - 20080718
IS  - 1107-3756 (Print)
IS  - 1107-3756 (Linking)
VI  - 22
IP  - 2
DP  - 2008 Aug
TI  - Inflammatory cytokine signaling in insulin producing beta-cells enhances the 
      colocalization correlation coefficient between L-type voltage-dependent calcium 
      channel and calcium-sensing receptor.
PG  - 155-63
AB  - The immunological processes in type 1 diabetes and metabolic/inflammatory 
      disorder in type 2 diabetes converge on common signaling pathway(s) leading to 
      beta-cell death in these two diseases. The cytokine-mediated beta-cell death 
      seems to be dependent on voltage-dependent calcium channel (VDCC)-mediated Ca2+ 
      entry. The Ca2+ handling molecular networks control the homeostasis of [Ca2+]i in 
      the beta-cell. The activity and membrane density of VDCC are regulated by several 
      mechanisms including G protein-coupled receptors (GPCRs). CaR is a 123-kDa seven 
      transmembrane extracellular Ca2+ sensing protein that belongs to GPCR family C. 
      Tumor necrosis factor-alpha (TNF-alpha), is a cytokine widely known to activate 
      nuclear factor-kappaB (NF-kappaB) transcription in beta-cells. To obtain a better 
      understanding of TNF-alpha-induced molecular interactions between CaR and VDCC, 
      confocal fluorescence measurements were performed on insulin-producing beta-cells 
      exposed to varying concentrations of TNF-alpha and the results are discussed in 
      the light of increased colocalization correlation coefficient. The insulin 
      producing beta-cells were exposed to 5, 10, 20, 30, and 50 ng/ml TNF-alpha for 24 
      h at 37 degrees . The cells were then immunolabelled with antibodies directed 
      against CaR, VDCC, and NF-kappaB. The confocal fluorescence imaging data showed 
      enhancement in the colocalization correlation coefficient between CaR and VDCC in 
      beta-cells exposed to TNF-alpha thereby indicating increased membrane delimited 
      spatial interactions between these two membrane proteins. TNF-alpha-induced 
      colocalization of VDCC with CaR was inhibited by nimodipine, an inhibitor of 
      L-type VDCC thereby suggesting that VDCC activity is required for spatial 
      interactions with CaR. The 3-D confocal fluorescence imaging data also 
      demonstrated that addition of TNF-alpha to RIN cells led to the translocation of 
      NF-kappaB from the cytoplasm to the nucleus. Such molecular interactions between 
      CaR and VDCC in tissues possibly provide control over Ca2+ channel activity via 
      direct protein-protein contact.
FAU - Parkash, Jai
AU  - Parkash J
AD  - Robert Stempel School of Public Health, Department of Environmental and 
      Occupational Health, Florida International University, Miami, FL 33199, USA. 
      parkashj@fiu.edu
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (Calcium Channels, L-Type)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, Calcium-Sensing)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Active Transport, Cell Nucleus/physiology
MH  - Animals
MH  - Calcium Channels, L-Type/*metabolism
MH  - Cell Line
MH  - Dose-Response Relationship, Drug
MH  - Inflammation/*metabolism
MH  - Insulin-Secreting Cells/cytology/*drug effects/metabolism
MH  - NF-kappa B/metabolism
MH  - Rats
MH  - Receptors, Calcium-Sensing/*metabolism
MH  - Signal Transduction
MH  - Statistics as Topic
MH  - Tumor Necrosis Factor-alpha/metabolism/*pharmacology
EDAT- 2008/07/19 09:00
MHDA- 2008/09/19 09:00
CRDT- 2008/07/19 09:00
PHST- 2008/07/19 09:00 [pubmed]
PHST- 2008/09/19 09:00 [medline]
PHST- 2008/07/19 09:00 [entrez]
PST - ppublish
SO  - Int J Mol Med. 2008 Aug;22(2):155-63.