Mitogen-activated protein kinase regulates FSH-induced expression of tissue-type plasminogen activator through an activator protein 1 response element

Cui-Ling Lu; Fu-Qing Yu; Tao Liu; Zhao-Yuan Hu; Yi-Xun Liu
December 2008
Endocrine (1355008X);Dec2008, Vol. 34 Issue 1-3, p101
Academic Journal
Abstract  We have analyzed a possible role of mitogen-activated protein kinase (MAPK) and activator protein-1 (AP-1) in the regulation of FSH-induced tissue type plasminogen activator (tPA) production in granulosa cells (GCs) prepared from DES-treated immature rats; Treatment of the cells in the presence of FSH with MAPK inhibitors, such as UO126 or SB203580, significantly decreased the FSH-induced tPA production, suggesting that multiple signaling pathways may be involved in FSH-regulated tPA expression. We further examined possible signaling action involved in FSH-activated ERK1/2 and p38 MAPK on tPA production, and observed that FSH receptor occupancy led to both ERK1/2 and p38 MAPK phosphorylation. Such action might be through a protein kinase A-dependent pathway because the observed activation was destroyed by the addition of its specific inhibitor H89 to the culture. The inhibition of ERK1/2 and p38 MAPK activation by their specific inhibitors remarkably reduced FSH-induced tPA mRNA and its protein production. We further examined whether AP-1 located in the tPA promoter is involved in FSH-regulated tPA production, and demonstrated that FSH significantly stimulated AP-1 expression, whereas inclusion of H89, UO126, or SB20358 in the culture significantly decreased FSH-induced AP-1 expression. In summary, FSH-induced ERK1/2 and p38 MAPK activation is capable of regulating tPA production in cultured primary GCs, and that the transcript factor AP-1 may be important in the regulation of FSH-induced tPA expression.


Related Articles

  • Role of P38 MAPK on MMP Activity in Photothrombotic Stroke Mice as Measured using an Ultrafast MMP Activatable Probe. Chang, Di; Wang, Yuan-Cheng; Bai, Ying-Ying; Lu, Chun-Qiang; Xu, Ting-Ting; Ju, Shenghong; Zhu, Lei // Scientific Reports;11/20/2015, p16951 

    Matrix metalloproteinases (MMPs) exert a dual effect in ischemic stroke and thus represent an ideal target for detection and therapy. However, to date, all clinical trials of MMP inhibitors have failed, and alternative drug candidates and therapeutic targets are urgently required. Nonetheless,...

  • BDNF-TrkB signaling through Erk1/2MAPK phosphorylation mediates the enhancement of fear memory induced by glucocorticoids. Revest, J-M; Le Roux, A; Roullot-Lacarrière, V; Kaouane, N; Vallée, M; Kasanetz, F; Rougé-Pont, F; Tronche, F; Desmedt, A; Piazza, P V // Molecular Psychiatry;Sep2014, Vol. 19 Issue 9, p1001 

    Activation of glucocorticoid receptors (GR) by glucocorticoid hormones (GC) enhances contextual fear memories through the activation of the Erk1/2MAPK signaling pathway. However, the molecular mechanism mediating this effect of GC remains unknown. Here we used complementary molecular and...

  • Plasma Levels of t-PA and PAI-1 Correlate With the Formation of Experimental Post-Surgical Peritoneal Adhesions. Di Filippo, Clara; Falsetto, Alessandro; De Pascale, Vito; Tufariello, Elisabetta; De Lucia, Domenico; Rossi, Francesco; D'Amico, Michele; Cennamo, Antonio // Mediators of Inflammation;1/1/2006, Vol. 2006, Special section p1 

    This study has evaluated whether systemic changes of plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) parallel the adhesions development and whether they could be used as predictors of adhesion risk. This has been studied in an animal model of post-surgical peritoneal...

  • TPA via Infusion Catheters Followed by Continuous IV Infusion for 3 Days Prevents Intimal Hyperplasia After Ballon Injury. Kanamasa, Ken; Inoue, Yoshikazu; Otani, Narutaka; Naito, Norikatsu; Morii, Hideki; Ikeda, Akiko; Taniguchi, Mitsugu; Ishida, Norihiro; Hayashi, Takahiro; Ishikawa, Kinji // Angiology;Dec2001, Vol. 52 Issue 12, p819 

    Examines the effects of tissue plasminogen activator (tPA) on the development of intimal hyperplasia. Observation on the intimal cross-sectional areas of the Dispatch catheterized groups; Comparison of intima ratios; Conclusion on the local delivery of tPA.

  • Pharmaceuticals. Greene, Jan; Serb, Chris // H&HN: Hospitals & Health Networks;04/05/97, Vol. 71 Issue 7, p21 

    Presents good news and bad news in a clinical trial of the cardiac drug digoxin. Medical effectiveness of tissue plasminogen activator (TPA); Treatment of stroke patients with TPA; Cost savings of the treatment.

  • Intravenous tissue plasminogen activator and size of infarct, left ventricular function, and survival in acute myocardial infarction. de Werf, Frans Van; Arnold, Alfred E.R. // BMJ: British Medical Journal (International Edition);11/26/88, Vol. 297 Issue 6660, p1374 

    Assesses the effect of intravenous recombinant tissue type plasminogen activator on the size of infarct, left ventricular function, and survival in acute myocardial infarction. Rate of ejection fraction after intravenous streptokinase; Limitation of expansion of the infarct and cardiac...

  • recombinant tPA.  // Taber's Cyclopedic Medical Dictionary (2009);2009, Issue 21, p1983 

    A definition of the term "recombinant tPA," which refers to tissue plasminogen activator, is presented.

  • In praise of informed scepticism. Godlee, Fiona // BMJ: British Medical Journal;6/22/2013, Vol. 346 Issue 7913, p4 

    An introduction is presented in which the editor discusses various reports within the issue on topics including financial conflicts of interest and physicians, guidelines for use of alteplase, a tissue plasminogen activator and abandoned trials.

  • Alteplase.  // Reactions Weekly;4/17/2010, Issue 1297, p9 

    The article describes the case of a 40-year-old man with end-stage renal disease and a history of coronary artery disease who developed intrapleural haemorrhage while receiving treatment with alteplase for a pleural effusion.


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics