Rabbit Anti-Human JUN (Phospho-Ser73) polyclonal antibody

Several microRNAs (miRNAs or miRs) regulate cerebral ischemic injury outcomes; however, little is known about the role of miR-539-5p during cerebral ischemic injury or the postischemic state. Cerebral ischemic injury was modeled in vitro by exposing human cortical neurons to oxygen-glucose deprivation (OGD) and in vivo by occluding the middle cerebral artery (MCAO) in a rat model. The effects of miR-539-5p. histone deacetylase 1 (HDAC1), and early growth response 2 (EGR2) on cerebral ischemia were investigated using gain- and loss-of-function experiments. We identified changes in miR-539-5p, HDAC1, EGR2, and phosphorylated c-Jun NH,-terminal kinase (JNK). The interaction among miR-539-5p, HDAC1, and EGR2 was determined by dual luciferase reporter gene assay, chromatin immunoprecipitation, and coimmunoprecipitation. We also investigated the effects on cell viability and apoptosis and changes in inflammatory cytokine expression and spatial memory on MCAO rats. miR-539-5p and EGR2 were poorly expressed, while HDAC1 was highly expressed in OGD-treated HCN-2 cells. miR-539-5p targeted HDAC1, while HDAC1 prevented acetylation of EGR2 resulting in its downregulation and subsequent activation of the JNK pathway. Overexpression of miR-539-5p or EGR2 or silencing HDAC1 improved viability and reduced apoptosis of OGD-treated HCN-2 cells in vitro. Furthermore, overexpression of miR-539-5p improved spatial memory, while decreasing cell apoptosis and inflammation in MCAO rats. Collectively, these data suggest that miR-539-5p targets HDAC1 to upregulate EGR2, thus blocking the JNK signaling pathway, by which cerebral ischemic injury is alleviated.

In ovaries, follicles undergo a periodic process of degeneration, namely atresia, during each stage of development. Granulosa cell (GC) apoptosis is believed as the hallmark of follicular atresia. The avascular environment within the granulosa compartment is supposed to cause hypoxic conditions. The effects of hypoxia on organs, tissues, cells can be either positive or negative, depending on the severity and context. The present study aimed to explore whether and how severe hypoxia under in vitro conditions functions in apoptosis of porcine GCs. The current results showed that the apoptosis in porcine GCs exposed to severe hypoxia (1% O-2) was correlated with enhanced activation of c-Jun N-terminal kinase (JNK), nuclear accumulation of FOXO1, as well as elevated level of cleaved caspase-3 and decreased ratio of BCL-2/BAX. Further investigations revealed that severe hypoxia-mediated JNK activation was required for the apoptotic death of porcine GCs and the nuclear transport of FOXO1. Moreover, inhibition of FOXO1 reduced GCs apoptosis upon severe hypoxia exposure. Together, these findings suggested that severe hypoxia might act through JNK/FOXO1 axis to induce apoptosis in porcine GCs. (C) 2020 Elsevier Inc. All rights reserved.