To demonstrate a direct interaction between USP8 and HIF-1α in OGD-treated PC12 cells, we performed co-immunoprecipitation assays and found that HIF-1α was precipitated by antibody against USP8, but not by control rabbit IgG (Figure 5B). Moreover, under OGD conditions, overexpression of Nrdp1 by Ad-Nrdp1 reduced co-immunoprecipitation between USP8 and HIF-1α, while knockdown of Nrdp1 by Ad-si-Nrdp1 enhanced the interaction between these two proteins (Figure 5C). These data indicate that under ischemic conditions, Nrdp1 upregulation may hinder the stabilization of HIF-1α in neurons via promoting ubiquitin-mediated degradation of USP8, thus attenuating cellular adaptive response to hypoxia/ischemia.