TY - JOUR
T1 - nSMase2 activation and trafficking are modulated by oxidative stress to induce apoptosis
AU - Levy, Michal
AU - Castillo, S. Sianna
AU - Goldkorn, Tzipora
PY - 2006/6/9
Y1 - 2006/6/9
N2 - We have previously shown that accumulation of ceramide, triggered by hydrogen peroxide (H2O2), 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 (H2O2) 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.
AB - We have previously shown that accumulation of ceramide, triggered by hydrogen peroxide (H2O2), 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 (H2O2) 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.
KW - Apoptosis
KW - Ceramide
KW - Glutathione
KW - Hydrogen peroxide
KW - Lung
KW - Neutral sphingomyelinase 2
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U2 - 10.1016/j.bbrc.2006.04.013
DO - 10.1016/j.bbrc.2006.04.013
M3 - Article
C2 - 16631623
AN - SCOPUS:33646127797
VL - 344
SP - 900
EP - 905
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -