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Related Experiment Videos

Mitogen-activated protein kinases regulate platelet-activating factor-induced hyperpermeability.

Peng Yu1, Takuya Hatakeyama, Haruo Aramoto

  • 1Division of Vascular Surgery, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Microcirculation (New York, N.Y. : 1994)
|November 15, 2005
PubMed
Summary

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Platelet-activating factor (PAF) triggers microvascular hyperpermeability. This study shows that extracellular signal-regulated kinases (ERK-1/2) and p38-mitogen-activated protein kinases (MAPK) are key regulators in this PAF-induced signaling cascade.

Area of Science:

  • Physiology
  • Molecular Biology
  • Pharmacology

Background:

  • Platelet-activating factor (PAF) is a potent lipid mediator.
  • PAF plays a critical role in inflammatory responses, including microvascular hyperpermeability.
  • The specific signaling pathways regulating PAF-induced microvascular leakage in vivo are not fully elucidated.

Purpose of the Study:

  • To investigate the role of p42/44- (ERK-1/2) and p38-mitogen-activated protein kinases (MAPK) in the PAF signaling cascade.
  • To determine if these kinases are in vivo regulatory elements in PAF-induced microvascular hyperpermeability.

Main Methods:

  • Utilized FITC-dextran 70 as a macromolecular tracer to assess microvascular permeability in mouse mesenteric fat tissue.
  • Measured interstitial integrated optical intensity (IOI) as an index of microvascular permeability.

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  • Employed specific inhibitors for ERK-1/2 (AG126) and p38-MAPK (SB203580) to evaluate their effects on PAF-induced hyperpermeability.

    • Main Results:

    • PAF application (10(-7) M) significantly increased IOI, indicating enhanced microvascular permeability.
    • Inhibition of ERK-1/2 with AG126 dose-dependently reduced PAF-induced IOI.
    • Inhibition of p38-MAPK with SB203580 also dose-dependently reduced PAF-induced IOI.

    Conclusions:

    • ERK-1/2 and p38-MAPK are integral components of the signaling pathway regulating PAF-induced microvascular hyperpermeability.
    • These findings highlight the involvement of specific MAPK pathways in PAF-mediated vascular leakage in vivo.
    • The study provides in vivo evidence for the regulatory role of ERK-1/2 and p38-MAPK in PAF signaling.