UV-C Light Induces Raft-associated Acid Sphingomyelinase and JNK Activation and Translocation Independently on a Nuclear Signal

Abstract

The initiation of UV light-induced signaling in mammalian cells is largely considered to be subsequent to DNA damage. Several studies have also described ceramide (CER), a lipid second messenger, as a major contributor in mediating UV light-induced c-Jun N-terminal kinase (JNK) activation and cell death. It is demonstrated here that UV-C light irradiation of U937 cells results in the activation and translocation of a Zn 2؉ -independent acid sphingomyelinase, leading to CER accumulation in raft microdomains. These CERenriched rafts aggregate and play a functional role in JNK activation. The observation that UV-C light also induced CER generation and the externalization of acid sphingomyelinase and JNK in human platelets conclusively rules out the involvement of a nuclear signal generated by DNA damage in the initiation of a UV light response, which is generated at the plasma membrane.

Signaling pathways from membrane lipid rafts to JNK1 activation in reactive nitrogen species-induced non-apoptotic cell death

“…Such observations are consistent with recent findings that translocation of JNK toward lipid raft microdomains occurred when U937 cell was treated with UV-C. 35 In addition, redistribution of MAP kinases, including extracellular signal-regulated kinase and p38, to lipid raft structures in stimulated neutrophils has also been reported, 38 suggesting that membrane lipid rafts may play a role in action of the MAPK family, depending on the study context, such as cell type and the nature of the stimulus. Apoptosis and non-apoptotic cell death/necrosis are two distinct forms of cell death and both are closely implicated in the pathological processes of human diseases.…”

“…Although TRAF2 is one of the key molecules in TNFR1 signaling pathway, 11,31 it appears that RNS acts on TRAF2 independent of TNFR1, based on our preliminary observation that tnfr1À/À MEF are as susceptible as WT MEF to RNSinduced cell death (data not shown). Lipid rafts, the liquidordered phase microdomains existing within membranes, have been reported involved in various signaling pathways triggered by numbers of stimuli, such as H 2 O 2 , 12,34 ultraviolet light (UV) 35 and TNFa. 36 Data from our study clearly support the notion that RNS promote the recruitment of TRAF2 into lipid rafts and then mediates JNK activation and subsequent cell death.…”

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

“…However, it has been recently shown that generation of reactive oxygen species an important step for aSMase activation in cells (Dumitru and Gulbins 2006;Charruyer et al 2005).The aSMase could be activated by the protein kinase Cδ (PKCδ), which is overexpressed under oxidative stress (Zeidan and Hannun 2007) and a premature aging disorderWerner syndrome (Massip et al 2010). Based on these results, reasonable assumption can be made that α-tocopherol prevents ceramide accumulation in the liver of old rats, at least in part, via the glutathionedependent nSMase and PKCδ-dependent aSMase inhibition.…”

Types A and B Niemann-Pick disease

“…Notably, when cells are subjected to stress, ASM rapidly translocates from lysosomes to the outer leaflet of the plasma membrane, where it also can hydrolyze sphingomyelin into ceramide [39,40]. This causes reorganization of membrane lipid microdomains, or "raft" structures, and stimulates downstream signaling events.…”