Oxidative stress can activate the epidermal platelet-activating factor receptor

Area of Science:

• Dermatology
• Cell Biology
• Biochemistry

Background:

• Platelet-activating factor (PAF) is a lipid mediator involved in skin inflammation and keratinocyte function.
• Keratinocytes produce PAF and possess functional PAF receptors linked to calcium signaling.
• Oxidative stress can trigger intracellular calcium (Ca2+) release, stimulating PAF biosynthesis.

Purpose of the Study:

• To investigate the role of epidermal PAF receptors in modulating oxidant-induced signaling pathways.
• To determine if PAF receptors influence the cellular response to oxidative stress in keratinocytes.

Main Methods:

• Utilized a cell model by transducing PAF receptor-negative KB epithelial cells with the PAF receptor.
• Exposed cells to the pro-oxidant tert-butyl hydroperoxide (t-BHP) to measure intracellular Ca2+ changes.
• Assessed the effects of PAF receptor antagonists (CV-6209, WEB 2086) and antioxidants (vitamin E, TMTU) on t-BHP-induced signaling.

Main Results:

• Expression of the PAF receptor in KB cells significantly reduced the threshold for t-BHP-induced Ca2+ flux and increased peak Ca2+ levels.
• PAF receptor antagonists and antioxidants inhibited the augmentation of t-BHP-induced Ca2+ mobilization.
• t-BHP treatment stimulated endogenous PAF synthesis in KB cells expressing the PAF receptor.

Conclusions:

• Epidermal PAF receptors play a significant role in mediating cellular responses to oxidative stress.
• PAF receptor signaling can amplify oxidant-induced calcium mobilization in keratinocytes, partly through endogenous PAF production.
• These findings highlight the involvement of PAF receptors in cutaneous responses to oxidative damage.