Zhiyun Wang

To explore the protection of naringenin against oxygen-glucose deprivation/reperfusion (OGD/R)-induced HT22 cell injury, a cell model of cerebral ischemia/reperfusion (I/R) injury in vitro, focusing on SIRT1/FOXO1 signaling pathway. Cytotoxicity, apoptosis, reactive oxygen species (ROS) generation, malondialdehyde (MDA) content, 4-hydroxynonenoic acid (4-HNE) level, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities were measured by commercial kits. Inflammatory cytokines levels were determined by enzyme-linked immunosorbent assay (ELISA). The protein expressions were monitored by Western blot analysis. Naringenin significantly ameliorated OGD/R-induced cytotoxicity and apoptosis in HT22 cells. Meanwhile, naringenin promoted SIRT1 and FOXO1 protein expressions in OGD/R-subjected HT22 cells. In addition, naringenin attenuated OGD/R-induced cytotoxicity, apoptosis, oxidative stress (the increased ROS, MDA and 4-HNE levels, and the decreased SOD, GSH-Px and CAT activities) and inflammatory response (the increased tumor necrosis factor-α, interleukin [IL]-1β, and IL-6 levels and the decreased IL-10 level), which were blocked by the inhibition of the SIRT1/FOXO1 signaling pathway induced by SIRT1-siRNA transfection. Naringenin protected HT22 cells against OGD/R injury depending on its antioxidant and anti-inflammatory activities via promoting the SIRT1/FOXO1 signaling pathway.

Death associated protein kinase 1 (DAPK1) was initially discovered in the progress of gamma‐interferon induced programmed cell death, it is a key factor in the central nervous system, including Parkinson's disease (PD). However, the underlying mechanisms of DAPK1 in PD remain unclear and this research work aims to explore the potential mechanisms of DAPK1 in PD. In the study, we exposed SH‐SY5Y cells to MPP⁺ and treated mice with MPTP to investigate the roles of DAPK1 in PD and the underlying mechanisms. The results indicated that the expression of DAPK1 is significantly upregulated and negatively correlated with miR‐124‐3p levels in SH‐SY5Y cells treated by MPP⁺, and miR‐124‐3p mimics could effectively inhibit DAPK1 expressions and alleviate MPP⁺‐induced cell apoptosis. In addition, knockdown MALAT1 reduces the levels of DAPK1 and the ratio of SH‐SY5Y cell apoptosis, which is reversed via miR‐124‐3p inhibitor in vitro. Similarly, knockdown MALAT1 could improve behavioral changes and reduce apoptosis by miR‐124‐3p upregulation and DAPK1 downregulation in MPTP induced PD mice. Taken together, our data showed that lncRNA MALAT1 positively regulates DAPK1 expression by targeting miR‐124‐3p, and mediates cell apoptosis and motor disorders in PD. In summary, these results suggest that MALAT1/miR‐124‐3p /DAPK1 signaling cascade mediates cell apoptosis in vitro and in vivo, which may provide experimental evidence of developing potential therapeutic strategies for PD.