Ceramide-enhanced urokinase-type plasminogen activator ( uPA) release is mediated by protein kinase C in cultured microglia.
As described previously, a relatively high dose of neurotrophins increased the release of urokinase-type plasminogen activator ( uPA) from cultured microglia. This biological response is suggested to be caused by ceramide, which is a metabolite of nerve growth factor low-affinity receptor (NGFRp75)-associated sphingomyelin turnover. Therefore, in the present study, we examined the effect of ceramide on the release of uPA from cultured microglia. Treatment of the cells with permeable C8-ceramide (D-erythro-Sphingosine, N-octanoyl-) enhanced uPA release in a dose-dependent manner. This effect of C8-ceramide was mimicked by treatment with bacterial sphingomyelinase. A pharmacological study using a specific PKC activator, phorbol-12-myristate-13-acetate, and a protein kinase C ( PKC) inhibitor, bisindolylmaleimide, showed that PKC activation is required in order to release uPA from ceramide-stimulated microglia as well as from nonstimulated microglia. Further study using a specific conventional PKC (cPKC) activator, 1-oleoyl-2-acetyl-sn-glycerol (OAG), and a specific cPKC inhibitor, Gö 6976, suggested that PKC-delta and/or -epsilon is involved in uPA release. As opposed to the apoptotic pathway, however, no activation of c-Jun N-terminal kinase and nuclear factor kappa B was observed in C8-ceramide-stimulated microglia. The findings suggest that uPA release from microglia is regulated by a mechanism in which PKC-delta and/or -epsilon are activated and further signals are transduced subsequently.[1]References
- Ceramide-enhanced urokinase-type plasminogen activator (uPA) release is mediated by protein kinase C in cultured microglia. Nakajima, K., Honda, S., Tohyama, Y., Kurihara, T., Kohsaka, S. Glia (2000) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
