2005
DOI: 10.1074/jbc.m414361200
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Abstract: CD95 ligand (CD95L) triggers a rapid formation of reactive oxygen species (ROS) as an upstream event of CD95 activation and apoptosis induction in rat hepatocytes. This ROS response was sensitive to inhibition by diphenyleneiodonium, apocynin, and neopterin, suggestive of an involvement of NADPH oxidases. In line with this, hepatocytes expressed mRNAs not only of the phagocyte gp91 phox (Nox 2), but also of the homologs Nox 1 and 4 and Duox 1 and 2, as well as the regulatory subunit p47 phox . gp91 phox (Nox 2… Show more

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Cited by 222 publications
(207 citation statements)
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References 83 publications
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“…This notion is consistent with a previous biochemical study (Qiu et al, 2003) indicating that oxidation of purified ASM at cysteine 629 results in stimulation and a disulfide bond-mediated dimerization A central role of ROS for the induction of apoptosis by CD95 has been previously reported (Gulbins et al, 1996;Um et al, 1996) and was recently confirmed by several studies (Reinehr et al, 2005;Yin, 2005). Experiments on hepatocytes demonstrated that an inhibitor of the ASM blocks the release of ROS suggesting that ROS functions downstream of the ASM (Reinehr et al, 2005;Yin, 2005). However, this is not in contrast to the present data, as we have previously shown that CD95 primarily induces a very weak stimulation of caspase 8 that results within seconds in the translocation and activation of the ASM and the formation of ceramide-enriched membrane domains that cluster CD95 .…”
Section: Discussionsupporting
confidence: 92%
See 1 more Smart Citation
“…This notion is consistent with a previous biochemical study (Qiu et al, 2003) indicating that oxidation of purified ASM at cysteine 629 results in stimulation and a disulfide bond-mediated dimerization A central role of ROS for the induction of apoptosis by CD95 has been previously reported (Gulbins et al, 1996;Um et al, 1996) and was recently confirmed by several studies (Reinehr et al, 2005;Yin, 2005). Experiments on hepatocytes demonstrated that an inhibitor of the ASM blocks the release of ROS suggesting that ROS functions downstream of the ASM (Reinehr et al, 2005;Yin, 2005). However, this is not in contrast to the present data, as we have previously shown that CD95 primarily induces a very weak stimulation of caspase 8 that results within seconds in the translocation and activation of the ASM and the formation of ceramide-enriched membrane domains that cluster CD95 .…”
Section: Discussionsupporting
confidence: 92%
“…Next, we aimed to identify molecular mechanisms of ASM-activation by TRAIL. Previous studies demonstrated a role of reactive oxygen species in the induction apoptosis by CD95 (Gulbins et al, 1996;Liu et al, 1996;Um et al, 1996;Yin, 2005;Reinehr et al, 2005). To test the hypothesis that the ASM is regulated by a redoxmechanism in vivo, we determined the release of reactive oxygen species (ROS) upon stimulation of BJAB or splenocytes with TRAIL for 1 min.…”
Section: Resultsmentioning
confidence: 99%
“…As noted above, PKC-phosphorylates the p47 phox subunit of NADPH oxidase, causing it to translocate to the membrane-bound NADPH oxidase components (11,12,42). We found that expression of a constitutively active PKCenhanced the expression of the p22 phox subunit of NADPH oxidase.…”
Section: Discussionmentioning
confidence: 65%
“…It could also involve PKC isozymes. Conventional PKC isozymes, PKC-␣ and -␤, novel PKC-␦, and atypical PKC-, phosphorylate the NADPH subunit, p47 phox , causing it to translocate to the membrane-bound NADPH subunits and activate NADPH oxidase (11,12,24,42). We and others have reported that high glucose increases the expression of the NADPH oxidase subunits, p22 phox and p47 phox , in mesangial cells in vitro and in vivo, in a PKCdependent manner (10,16,24,63).…”
mentioning
confidence: 99%
“…All these different challenges trigger the activation of the Src family kinase Yes in liver parenchymal cells (10,54,89) . The detailed mechanisms of hyperosmolarity-induced ROS formation have been discussed in detail above (see also Figure 2A) and resemble those triggered by CD95L (89) or hydrophobic bile acids (75,76) .…”
Section: Src Family Kinases and Apoptosismentioning
confidence: 99%