UVA Radiation Stimulates Ceramide Production: Relationship to Oxidative Stress and Potential Role in ERK, JNK, and p38 Activation

7-Dehydrocholesterol enhances ultraviolet A-induced oxidative stress in keratinocytes: Roles of NADPH oxidase, mitochondria, and lipid rafts

“…An alternative mechanism involves ceramide because it is released in keratinocytes by UVA [7,57] and has been reported to activate NADPH oxidase in endothelial cells [58]. The reported time course for UVA-stimulated release of ceramide in normal keratinocytes [7,57] appears to be too slow to cause the rapid increase in NADPH oxidase activity that we measured in SLO-HK (Fig. 3), although more rapid kinetics for ceramide release might be found in SLO-HK.…”

“…Activation of growth factor receptors stimulates NADPH oxidase activity in many cells types [54][55][56].However, UVA-induced activation of NADPH oxidase is unlikely to involve activation of EGFR because UVA inhibits signaling via EGFR [54]. An alternative mechanism involves ceramide because it is released in keratinocytes by UVA [7,57] and has been reported to activate NADPH oxidase in endothelial cells [58]. The reported time course for UVA-stimulated release of ceramide in normal keratinocytes [7,57] appears to be too slow to cause the rapid increase in NADPH oxidase activity that we measured in SLO-HK (Fig.…”

Vitamin E prevents the age-dependent and palmitate-induced disturbances of sphingolipid turnover in liver cells

“…Long-term feeding of the old rats with α-tocopherol or addition of the antioxidant to the culture media of hepatocytes significantly increased the level of the newly synthesized SM and reduced the newly synthesized ceramide content in the liver cells. Previous studies have demonstrated that the production of ceramide in [ 14 C]palmitate-labeled human keratinocytes was parallel to the level of reactive oxygen species, and the free radical scavenger vitamin E prevented the pro-oxidant (UVA radiation) effect on sphingolipid accumulation (Mazière et al 2001;Grether-Beck et al 2005). Moreover, UVAinduced ceramide accumulation could be prevented by inhibitors of key enzymes of sphingolipid synthesis de novo (myriocin) and ceramide synthesis (fumonisin B1), but not by glucosylceramide inhibitor (D,L-threo-PDMP; Grether-Beck et al 2005).…”

“…Vitamin E prevents the solar ultraviolet (UVA)-mediated non-enzymatic pathway of ceramide formation in long-term cultured, normal human keratinocytes (Grether-Beck et al 2000). However, under other experimental conditions, a direct cleavage of SM to ceramide by UVA was not observed in the human keratinocytes, while vitamin E pretreatment of the cells prevented UVA-induced ceramide accumulation (Mazière et al 2001). Addition of a high dose of vitamin E to the culture media before reoxygenation and hypoxia of cortical neurons significantly reduced nSMase activity and increased the level of negative regulator of the nSMase, glutathione, in cells of stroke-prone spontaneously hypertensive and Wistar Kyoto rats (Yamagata et al 2009).…”

The role of p38 in UVA-induced cyclooxygenase-2 expression in the human keratinocyte cell line, HaCaT

“…UVA regulates the expression of various genes including heme oxygenase-1, matrix metalloproteinase-1, IL-1a/b, IL-6, intracellular adhesion molecule, STAT3, AP-1 and AP-2 (Basu- Modak and Tyrrell, 1993;Grether-Beck et al, 1996;Klotz et al, 1999;Maziere et al, 2001;Scharffetter-Kochanek et al, 1993;Wlaschek et al, 1997;Zhang et al, 2001b;Silvers and Bowden, 2002). Considerable work is currently underway to elucidate the signal transduction mechanisms that are induced by UVA.…”