PMID- 12475794
OWN - NLM
STAT- MEDLINE
DCOM- 20030108
LR  - 20190516
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 51 Suppl 3
DP  - 2002 Dec
TI  - Activation of nuclear factor-kappaB by depolarization and Ca(2+) influx in MIN6 
      insulinoma cells.
PG  - S484-8
AB  - The purpose of the current study was to determine whether nuclear factor-kappaB 
      (NF-kappaB) activation is a component of the depolarization/Ca(2+)-dependent 
      signaling in beta-cells. MIN6 cells were transfected with a plasmid containing 
      five tandem repeats of NF-kappaB binding sites linked to a luciferase reporter. 
      The results of these experiments showed that KCl induced depolarization-activated 
      NF-kappaB-dependent transcription (3.8-fold at 45 mmol/l, P < 0.01) in a 
      concentration-dependent manner. Tumor necrosis factor-alpha (TNF-alpha), a known 
      inducer of NF-kappaB signaling, activated this construct by 3.4-fold (P < 0.01). 
      The response of NF-kappaB to depolarization was inhibited by the Ca(2+)-channel 
      blocker verapamil and by the mitogen-activated protein kinase kinase (MEK) 
      inhibitor PD98059 (70 and 62%, respectively). TNF-alpha, glucose, and KCl 
      treatment resulted in inhibitory kappaBalpha degradation by Western blot 
      analysis. TNF-alpha treatment and depolarization activation of NF-kappaB differed 
      significantly in that TNF-alpha activation was not blocked by PD98059. 
      Transfection with PKA, MEK, and MEK kinase induced NF-kappaB-dependent 
      transcription by 20-, 90-, and 300-fold, respectively, suggesting that these 
      pathways contribute to the activation in the depolarization response. These 
      findings demonstrate that depolarization/Ca(2+) influx, as well as TNF-alpha 
      treatment, can activate NF-kappaB-dependent transcription in pancreatic 
      beta-cells, but by different signaling pathways. The current studies show that 
      Ca(2+) signals in pancreatic beta-cells can activate transcription factors 
      involved in the regulation of cell cycle and apoptosis. These findings now add 
      NF-kappaB to the list of depolarization-induced transcription factors in 
      pancreatic beta-cells.
FAU - Bernal-Mizrachi, Ernesto
AU  - Bernal-Mizrachi E
AD  - Washington University School of Medicine, Division of Endocrinology, Diabetes and 
      Metabolism, St. Louis, Missouri, USA. ebernal@im.wustl.edu
FAU - Wen, Wu
AU  - Wen W
FAU - Shornick, Michael
AU  - Shornick M
FAU - Permutt, M Alan
AU  - Permutt MA
LA  - eng
GR  - DK16746/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Flavonoids)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 660YQ98I10 (Potassium Chloride)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
RN  - IY9XDZ35W2 (Glucose)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium/*metabolism
MH  - Electrophysiology
MH  - Enzyme Inhibitors/pharmacology
MH  - Flavonoids/pharmacology
MH  - Glucose/pharmacology
MH  - I-kappa B Proteins/metabolism
MH  - Insulinoma/genetics/*metabolism/*physiopathology
MH  - Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors
MH  - NF-kappa B/*physiology
MH  - Potassium Chloride/pharmacology
MH  - Time Factors
MH  - Transcription, Genetic/drug effects
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/pharmacology
EDAT- 2002/12/12 04:00
MHDA- 2003/01/09 04:00
CRDT- 2002/12/12 04:00
PHST- 2002/12/12 04:00 [pubmed]
PHST- 2003/01/09 04:00 [medline]
PHST- 2002/12/12 04:00 [entrez]
AID - 10.2337/diabetes.51.2007.s484 [doi]
PST - ppublish
SO  - Diabetes. 2002 Dec;51 Suppl 3:S484-8. doi: 10.2337/diabetes.51.2007.s484.