Mitogen-activated protein kinase (p38-, JNK-, ERK-) activation pattern induced by extracellular and intracellular singlet oxygen and UVA

Ultraviolet A (UVA; 320-400 nm) radiation in human skin fibroblasts induces a pattern of mitogen activated protein kinase (MAPK) activation consisting of a rapid and transient induction of p38 and c-Jun-N-terminal kinase (JNK ) activity but not extracellular signal-regulated kinases (ERK). UVA activa tion of p38 can be inhibited by the singlet oxygen (O-1(2)) quenchers azide and imidazole, but not by the hydroxyl radical scavengers mannitol or dime thylsulfoxide, pointing to the involvement of O-1(2). The same effect has b een shown for JNK. Like UVA, O-1(2) generated intracellularly upon photoexc itation of Rose Bengal activates p38 and JNK but not ERK. p38 and JNK activ ation was also elicited by chemiexcitation for the intracellular generation of O-1(2) by the lipophilic 1,4-endoperoxide of N,N'-di(2,3-dihydroxypropy l)-1,4-naphthalene dipropionamide. In contrast, extracellular generation of O-1(2), by irradiation of Rose Bengal immobilized on agarose beads or by c hemiexcitation employing the hydrophilic 1,4-endoperoxide of disodium 3,3'- (1,4-naphthylidene) dipropionate, was ineffective in activating p38 or JNK. These data suggest that the activation of p38 and JNK by O-1(2) occurs onl y when the electronically excited molecule is generated intracellularly.