PMID- 17721610
OWN - NLM
STAT- MEDLINE
DCOM- 20071025
LR  - 20220310
IS  - 0340-6245 (Print)
IS  - 0340-6245 (Linking)
VI  - 98
IP  - 2
DP  - 2007 Aug
TI  - CREB binding to the hypoxia-inducible factor-1 responsive elements in the 
      plasminogen activator inhibitor-1 promoter mediates the glucagon effect.
PG  - 296-303
AB  - Plasminogen activator inhibitor-1 (PAI-1) controls the regulation of the 
      fibrinolytic system in blood by inhibiting both urokinase-type and tissue-type 
      plasminogen activators. Enhanced levels of PAI-1 are related to pathological 
      conditions associated with hypoxia or hyperinsulinemia. In this study, we 
      investigated the regulation of PAI-1 expression by glucagon and the cAMP/PKA/CREB 
      signalling pathway in the liver. Stimulation of the cAMP/PKA/CREB signalling 
      cascade by starvation in vivo or glucagon in vitro induced PAI-1 gene expression 
      in liver. Furthermore, this response was associated with enhanced phosphorylation 
      of CREB. By using EMSAs we found that three promoter elements, the HRE2, E-box 4 
      and E-box 5, were able to bind CREB but only the HRE2 and E5 appeared to be 
      functionally active. Reporter gene assays confirmed that cAMP induced PAI-1 gene 
      transcription via the same element in both human and rat promoters. 
      Interestingly, although the HRE2 was involved, the glucagon/cAMP pathway had no 
      influence on hypoxia-inducible factor-1 (HIF-1) mRNA and protein levels. Thus, 
      CREB binding to the HIF-1 responsive elements in PAI-1 promoter mediates the 
      glucagon effect in the liver.
FAU - Dimova, Elitsa Y
AU  - Dimova EY
AD  - Department Chemistry/Biochemistry, University of Kaiserslautern, Kaiserslautern, 
      Germany.
FAU - Jakubowska, Malgorzata M
AU  - Jakubowska MM
FAU - Kietzmann, Thomas
AU  - Kietzmann T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Thromb Haemost
JT  - Thrombosis and haemostasis
JID - 7608063
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Plasminogen Activator Inhibitor 1)
RN  - 0 (RNA, Messenger)
RN  - 9007-92-5 (Glucagon)
RN  - E0399OZS9N (Cyclic AMP)
SB  - IM
MH  - Animals
MH  - Cyclic AMP/pharmacology
MH  - Cyclic AMP Response Element-Binding Protein/*metabolism
MH  - Glucagon/*physiology
MH  - Humans
MH  - Hypoxia-Inducible Factor 1/*genetics
MH  - Liver/metabolism
MH  - Phosphorylation
MH  - Plasminogen Activator Inhibitor 1/*genetics
MH  - *Promoter Regions, Genetic
MH  - Protein Binding
MH  - RNA, Messenger/analysis
MH  - Rats
MH  - *Response Elements
MH  - Transcription, Genetic
EDAT- 2007/08/28 09:00
MHDA- 2007/10/27 09:00
CRDT- 2007/08/28 09:00
PHST- 2007/08/28 09:00 [pubmed]
PHST- 2007/10/27 09:00 [medline]
PHST- 2007/08/28 09:00 [entrez]
AID - 07080296 [pii]
PST - ppublish
SO  - Thromb Haemost. 2007 Aug;98(2):296-303.