Lipid rafts and the oxidative stress hypothesis.

摘要

Epidermal keratinocytes undergo a complex differentiation program during which their cholesterol synthesis is consistently increased, cholesterol being a crucial element for the elaboration of the epidermal lipid barrier. Cholesterol is also an essential component of all animal plasma membranes and is required for the formation of membrane rafts, which are also named lipid rafts (Valencia et al., 2006). Lipid rafts regroup numerous signaling molecules, and their disruption after cholesterol depletion induces drastic changes in cellular signal transduction (Simons and Toomre, 2000). In previous studies published in this journal, we investigated lipid rafts in keratinocytes by using the cholesterol chelator methyl-beta-cyclodextrin (MBCD) and found that lipid raft perturbation is responsible for an altered epidermal phenotype characterized by accelerated involucrin and delayed keratin 10 expression Cans et al., 2004; Mathay et al., 2008). The activation of p38 mitogen-activated protein kinase was found to be a prerequisite for this alteration. Intriguing parallels in the response of keratinocytes that were either depleted in cholesterol or treated with H_2O_2 were identified; that is, both treatments, in a very similar time-course manner, increased the phosphorylation of p38 mitogen-activated protein kinase and induced the expression of heparin-binding EGF-like growth factor, a growth factor involved in epidermal homeostasis, at messenger RNA and protein levels. These data led us to hypothesize a role of oxidative mechanisms behind MBCD-induced effects (Mathay et al., 2008).