Role of epidermal growth factor receptor transactivation in the activation of cytosolic phospholipase A2 in leptin protection of salivary gland acinar cells against ethanol cytotoxicity

• Autorzy: Slomiany B.L. , Slomiany A.
• Języki publikacji: EN

Abstrakty

EN

A pleiotropic hormone, leptin, secreted into saliva by the acinar cells of salivary glands is an important mediator of the processes of oral mucosal defense. Here, we report on the role of epidermal growth factor receptor (EGFR) transactivation in the signaling events that mediate leptin protection of sublingual salivary gland acinar cells against ethanol cytotoxicity. We show that the protective effect of leptin against ethanol cytotoxicity was associated with the increased EGFR protein tyrosine kinase and cytosolic phospholipase A2 (cPLA2) activity, and characterized by a marked increase in matrix metalloproteinase MMP-9 and arachidonic acid (AA) release, and PGE2 generation. The loss in countering capacity of leptin against ethanol cytotoxicity was attained with JAK inhibitor AG490, Src inhibitor PP2, and EGFR inhibitor AG1478, as well as ERK inhibitor PD98059. Moreover, the agents evoked also the inhibition in leptin-induced up-regulation in cPLA2 activity, AA release, and PGE2 generation. The changes caused by leptin in EGFR phosphorylation, MMP-9, and cPLA2 activation were susceptible to suppression by metalloprotease inhibitor GM6001, but the production of MMP-9 was not affected by EGFR inhibitor AG1478 or PKC inhibitor Ro318220. These findings point to the involvement of MMP-9 in the event of leptin-induced EGFR transactivation that results in the signaling cascade leading to cPLA2 activation and up-regulation in PGE2 generation, thus providing new insights into the mechanism of oral mucosal protection against ethanol toxicity.

Słowa kluczowe

EN

acinar cell; prostaglandin E2; epidermal growth factor receptor transactivation; cytosolic phospholipase A2; salivary gland; leptin; activation; ethanol cytotoxicity

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology
• Rocznik: 2009
• Tom: 60
• Numer: 2
• Opis fizyczny: p.49-55,fig.,ref.

Twórcy

autor

Slomiany B.L.

• Research Center University of Medicine and Dentistry of New Jersey, Newark, NJ 07103-2400, USA

autor

Slomiany A.