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A previous study by our group indicated that receptor-interacting proteins (RIPs) are crucial in mediating necroptosis in developing neurons. However, whether this mechanism is involved in OPCs death is unclear. We aimed to explore the mechanisms of RIP-mediated oligodendrocytes (OLs) death in the developing brain. Oligodendrocytes necroptosis was induced by oxygen-glucose deprivation plus caspase inhibitor zVAD treatment (OGD\/zVAD) <jats:italic>in vitro<\/jats:italic>. Western blotting and immunofluorescence were used to detect RIPK1, RIPK3, mixed lineage kinase domain-like protein (MLKL), and Ca<jats:sup>2+<\/jats:sup> and calmodulin-dependent protein kinase II<jats:italic>\u03b4<\/jats:italic> (CaMKII<jats:italic>\u03b4<\/jats:italic>). Immunoprecipitation was used to assess the interactions between RIPK3 and RIPK1, MLKL, and CaMKII<jats:italic>\u03b4<\/jats:italic>. Necrostatin-1 was used to disturb the RIPK3\u2013RIPK1 interaction, and siRNA was used to inhibit RIPK3 or MLKL expression. Oligodendrocytes death was examined using PI staining, EM, and cell membrane leakage assays. <jats:italic>In vivo<\/jats:italic>, brain damage in neonatal rats was induced by hypoxia\u2013ischemia (HI). This was followed by an examination of myelin development. We found that OGD\/zVAD treatment upregulates the expression of RIPK3 and the interaction of RIPK3 with RIPK1, MLKL, and CaMKII<jats:italic>\u03b4<\/jats:italic>. Inhibition of the RIPK3-MLKL or RIPK3-CaMKII<jats:italic>\u03b4<\/jats:italic> interaction attenuates OLs death induced by OGD\/zVAD. These protective mechanisms involve the translocation of MLKL to the OLs membrane, and the phosphorylation of CaMKII<jats:italic>\u03b4<\/jats:italic>. However, inhibition of the RIPK3\u2013RIPK1 interaction did not protect OLs death induced by OGD\/zVAD. <jats:italic>In vivo<\/jats:italic> studies indicated that the disrupted development of myelin was attenuated after the inhibition of RIPK3-MLKL or RIPK3-CaMKII<jats:italic>\u03b4<\/jats:italic> interaction. Taken together, our data indicate that RIPK3 is a key factor in protection against OLs death and abnormal myelin development via its interaction with MLKL and CaMKII<jats:italic>\u03b4<\/jats:italic> after HI. This suggests that RIPK3 may be a potential target for the treatment of WMI in neonates.<\/jats:p>","DOI":"10.1038\/cddis.2017.54","type":"journal-article","created":{"date-parts":[[2017,2,23]],"date-time":"2017-02-23T13:47:22Z","timestamp":1487857642000},"page":"e2629-e2629","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["RETRACTED ARTICLE: RIPK3 interactions with MLKL and CaMKII mediate oligodendrocytes death in the developing brain"],"prefix":"10.1038","volume":"8","author":[{"given":"Yi","family":"Qu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huiqing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiping","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fengyan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Q","family":"Richard Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dezhi","family":"Mu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,2,23]]},"reference":[{"key":"BFcddis201754_CR1","doi-asserted-by":"publisher","first-page":"e7976","DOI":"10.1136\/bmj.e7976","volume":"345","author":"KL Costeloe","year":"2012","unstructured":"Costeloe KL, Hennessy EM, Haider S, Stacey F, Marlow N, Draper ES . 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