Rabbit Anti-Human JUN (Phospho-Thr91) polyclonal antibody

Parkinson's disease is a progressive neurodegenerative disease for which prevention and effective treatments are lacking. The pathogenesis of Parkinson's disease is not clearly understood. It is thought to be caused by oxidative stress-dependent loss of dopamine neurons in the substantia nigra and the promotion of inflammatory responses by microglia at the lesion site. In addition, cell loss occurs in the hypothalamus of Parkinson's disease patients. Carnosine is an endogenous dipeptide that can exert many beneficial effects, including an antioxidant action, metal ion chelation, proton buffering capacity, and inhibition of protein carbonylation and glycolysis. Previously, we found that carnosine inhibits trace metal-induced death of immortalized hypothalamic neuronal GT1-7 cells. In this study, we analyzed the efficacy of carnosine on 6-hydroxydopamine (6-OHDA)-dependent GT1-7 cell death and inflammatory responses. We found that carnosine significantly prevented 6-OHDA-dependent GT1-7 cell death in a dose-dependent manner. Moreover, carnosine significantly suppressed the expression of 6-OHDA-induced integrated stress response (ISR)-related factors and pro-inflammatory cytokines. Carnosine also significantly inhibited 6-OHDA-dependent reactive oxygen species (ROS) production and c-Jun amino-terminal kinase (JNK) pathway activation in GT1-7 cells. These results indicate that carnosine inhibits hypothalamic neuronal cell death and inflammatory responses by inhibiting the ROS-JNK pathway. We therefore suggest that carnosine may be effective in preventing the onset or the exacerbation of Parkinson's disease.

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.