PMID- 10955916
OWN - NLM
STAT- MEDLINE
DCOM- 20001204
LR  - 20211203
IS  - 0931-041X (Print)
IS  - 0931-041X (Linking)
VI  - 14
IP  - 8-9
DP  - 2000 Aug
TI  - Isoproterenol inhibits fibroblast growth factor-2-induced growth of renal 
      epithelial cells.
PG  - 726-34
AB  - The signal transduction pathways modulating bFGF effects in renal tubular 
      epithelial cells (RTEc) are not completely understood. Since the cAMP and the 
      mitogen-activated protein kinase (MAPK) pathways can modulate the growth of RTEc, 
      we studied whether two cAMP elevating agents, isoproterenol and 8-bromo-cAMP, 
      would modulate basic fibroblast growth factor (bFGF) induction of MAPK activity 
      (ERK-2) and cell proliferation in human renal proximal tubular epithelial cells 
      (RPTEc) and Madin-Darby canine kidney cells (MDCK clone EI1). Isoproterenol, but 
      not bFGF, stimulated cAMP production in RPTEc and MDCKEI1 cells. bFGF, 
      isoproterenol, and 8-bromo-cAMP alone increased ERK-2 activity in both cell 
      types. However, isoproterenol and 8-bromo-cAMP partially inhibited the bFGF 
      induction of ERK-2 activity, but only isoproterenol inhibited the proliferation 
      of both cell types. PD098059 (25 microM), an inhibitor of MAPK kinase (MEK 1/2), 
      blocked the bFGF mitogenic effects, but did not affect the 8-bromo-cAMP-induced 
      mitogenic effects in MDCKEI1 cells. These findings suggest that activation of 
      ERK-2 is required but not sufficient for mitogenesis in RTEc. We conclude that 
      isoproterenol inhibits the growth-promoting effects of bFGF in RTEc via 
      MEK-dependent and -independent pathways.
FAU - Izevbigie, E B
AU  - Izevbigie EB
AD  - Children's Research Institute, Children's National Medical Center, The George 
      Washington University, Washington, DC 20010, USA.
FAU - Gutkind, J S
AU  - Gutkind JS
FAU - Ray, P E
AU  - Ray PE
LA  - eng
GR  - DK49419-S1/DK/NIDDK NIH HHS/United States
GR  - R0-1DK 4919/DK/NIDDK NIH HHS/United States
GR  - R0-1HL 55605/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Germany
TA  - Pediatr Nephrol
JT  - Pediatric nephrology (Berlin, Germany)
JID - 8708728
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Flavonoids)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
RN  - 23583-48-4 (8-Bromo Cyclic Adenosine Monophosphate)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.1.- (MAP2K2 protein, human)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 1)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 2)
RN  - EC 2.7.12.2 (MAP2K1 protein, human)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
RN  - L628TT009W (Isoproterenol)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - 8-Bromo Cyclic Adenosine Monophosphate/pharmacology
MH  - Animals
MH  - Cell Division/drug effects
MH  - Cell Line
MH  - Cells, Cultured
MH  - Cyclic AMP/*metabolism
MH  - Dogs
MH  - Enzyme Inhibitors/pharmacology
MH  - Fibroblast Growth Factor 2/antagonists & inhibitors/*pharmacology
MH  - Flavonoids/pharmacology
MH  - Humans
MH  - Isoproterenol/*pharmacology
MH  - Kidney/cytology/*drug effects/metabolism
MH  - MAP Kinase Kinase 1
MH  - MAP Kinase Kinase 2
MH  - Mitogen-Activated Protein Kinase Kinases/metabolism
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Protein-Tyrosine Kinases/metabolism
MH  - Urothelium/cytology/drug effects/metabolism
EDAT- 2000/08/24 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/08/24 11:00
PHST- 2000/08/24 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/08/24 11:00 [entrez]
AID - 10.1007/pl00013426 [doi]
PST - ppublish
SO  - Pediatr Nephrol. 2000 Aug;14(8-9):726-34. doi: 10.1007/pl00013426.