Ishikawa, Makoto; Takaseki, Sanae; Yoshitomi, Takeshi; Covey, Douglas F.; Zorumski, Charles F.; Izumi, Yukitoshi published the artcile< The neurosteroid allopregnanolone protects retinal neurons by effects on autophagy and GABRs/GABAA receptors in rat glaucoma models>, Quality Control of 1223001-51-1, the main research area is neurosteroid allopregnanolone GABR GABA receptor rat glaucoma model; Allopregnanolone; autophagy; glaucoma; intraocular pressure; neurosteroid.
In an ex vivo rat glaucoma model using dissected retinas, the neurosteroid allopregnanolone (AlloP) protects retinal ganglion cells (RGCs) via GABR/GABAA receptors. To determine the involvement of macroautophagy/autophagy in neuroprotection by AlloP, we examined the effects of autophagy activators, rapamycin and torin 2, and autophagy inhibitors, bafilomycin A1 and SAR405, on retinal retinal morphol. and expression of MAP1 LC3B/LC3B (microtubule-associated protein 1 light chain 3 beta) and SQSTM1 (sequestosome 1). Administration of rapamycin or torin 2 exerted partial histol. neuroprotection, while combined administration of AlloP with bafilomycin A1 or SAR405 induced severe degeneration in a hyperbaric condition. Electron microscopic analyses showed that the addition of AlloP significantly increased autophagosomes and degenerative autophagic vacuoles in the retinal nerve fiber layer. Immunoblotting showed that the addition of AlloP or autophagic activators increased the lipidated form of LC3B (LC3B-II) and suppressed SQSTM1. Moreover, bafilomycin A1 increased LC3B-II and SQSTM1 protein levels in the presence of AlloP without changes in corresponding mRNAs compared to AlloP-treated retinas in a hyperbaric condition. These data indicate that AlloP likely induces a protective form of autophagy in this model. In an in vivo rat model of glaucoma, we also observed neuroprotective effects of AlloP. Injection of polystyrene microbeads into the anterior chamber increased intraocular pressure about 3-fold and induced RGC apoptosis. A single intravitreal injection of AlloP or autophagy activators prevented apoptosis and protected RGCs with autophagy activation. We conclude that AlloP may serve as a potential therapeutic agent for the treatment of glaucoma via diverse mechanisms.
Autophagy published new progress about Apoptosis. 1223001-51-1 belongs to class naphthyridine, and the molecular formula is C24H15F3N4O, Quality Control of 1223001-51-1.
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1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem