Involvement of endothelins in neuroprotection of valosin-containing protein modulators against retinal ganglion cell damage

Abstract

We have previously shown that Kyoto University Substances (KUSs), valosin-containing protein (VCP) modulators, suppress cell death in retinal ganglion cells of glaucoma mouse models through alterations of various genes expressions. In this study, among the genes whose expression in retinal ganglion cells was altered by KUS treatment in the N-methyl-d-aspartic acid (NMDA) injury model, we focused on two genes, endothelin-1 (Edn1) and endothelin receptor type B (Ednrb), whose expression was up-regulated by NMDA and down-regulated by KUS treatment. First, we confirmed that the expression of Edn1 and Ednrb was upregulated by NMDA and suppressed by KUS administration in mice retinae. Next, to clarify the influence of KUSs on cell viability in relation to the endothelin signaling, cell viability was examined with or without antagonists or agonists of endothelin and with or without KUS in 661W retinal cells under stress conditions. KUS showed a significant protective effect under glucose-free conditions and tunicamycin-induced stress. This protective effect was partially attenuated in the presence of an endothelin antagonist or agonist under glucose-free conditions. These results suggest that KUSs protect cells partially by suppressing the upregulated endothelin signaling under stress conditions.

Protective effect of ginsenoside Rg1 on 661W cells exposed to oxygen-glucose deprivation/reperfusion via keap1/nrf2 pathway

“…Rg1 has been found to have protective effects on various tissues and organs in the human body, with anti-apoptotic, anti-inflammatory and anti-aging effects. Previous studies have shown that Rg1 exerts various pharmacological effects through various mechanisms such as inhibition of apoptosis-related protein levels, downregulation of inflammatory mediators and anti-oxidation, effectively exerting organ-protective effects against I/R induced damage [9][10] . Some studies have reported that Rg1 can reduce the release of reactive oxygen stress and lactate dehydrogenase in a hypoxia-reperfusion model of cardiomyocytes, thereby improving the ability of cardiomyocytes to resist I/R injury.…”