title: nSMase2 activation and trafficking are modulated by oxidative stress to induce apoptosis.
abstract: We have previously shown that accumulation of ceramide, triggered by hydrogen peroxide (H(2)O(2)), induces apoptosis of human airway epithelial (HAE) cells. Under oxidant exposure, a lung sphingomyelinase (SMase) is activated and displays continued ceramide generation and pro-apoptotic signaling, thus leading to the pathological apoptosis that causes lung injury. In a search for a specific SMase that is modulated by oxidative stress, we recently cloned nSMase2 from monkey lung tissue and HAE cells. Here, we show that this nSMase2 is up-regulated by an oxidant (H(2)O(2)) and is inhibited by an antioxidant (glutathione (GSH)). Moreover, nSMase2 subcellular localization is governed by oxidant exposure, which leads to its preferential trafficking to the plasma membrane, where it generates ceramide and induces apoptosis. On the other hand, exposure to GSH results in nSMase2 trafficking to the nucleus, where it neither generates ceramide nor induces apoptosis.
authors.affiliation: Signal Transduction Laboratory, Department of Internal Medicine, University of California, School of Medicine, Davis, CA 95616, USA.
authors.forename: Michal
authors.initials: M
authors.lastname: Levy
authors.forename: S Sianna
authors.initials: SS
authors.lastname: Castillo
authors.forename: Tzipora
authors.initials: T
authors.lastname: Goldkorn
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D004789:Enzyme Activation; D006801:Humans; D018384:Oxidative Stress / Q000502:physiology*; D021381:Protein Transport / Q000502:physiology; D020545:Respiratory Mucosa / Q000166:cytology* / Q000201:enzymology*; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism*
chemical_list: C491484:SMPD3 protein, human; D013108:Sphingomyelin Phosphodiesterase