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• W2072421347 abstract "AbstractCa2+ is an essential second messenger, playing a fundamental role in maintaining cell viability and neuronal activity. Two specific endoplasmic reticulum calcium channels, ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate receptors (IP3Rs) play an important role in Ca2+ regulation. In the present study, we provided a 3D structure of RyR and IP3R by homology modeling, and we predicted their interactions with a known neuroprotective compound, 3-thiomethyl-5,6-(dimethoxyphenyl)-1,2,4-triazine (TDMT), as well as two inhibitors, dantrolene and 2-aminoethoxydiphenyl borate (2-APB). Interestingly, we found that dantrolene and 2-APB can bind to the IP3-binding domain of IP3R and RyR, while TDMT may directly block both channels by interacting with the putative resident domains in the pore. Cell culture experiments showed that these compounds could protect PC12 cells against H2O2-induced apoptosis and activate autophagic pathways. Collectively, our computational (in silico) and cell culture studies suggest that RyR and IP3R are novel and promising targets to be used against neurodegenerative diseases.Keywords: 2-APBapoptosisautophagycalciumdantroleneendoplasmic reticulumIP3RRyRPC12 cells AcknowledgmentsThis study was supported by Shahid Beheshti University of Medical Sciences Research Funds. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." @default.
• W2072421347 created "2016-06-24" @default.
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• W2072421347 date "2013-07-08" @default.
• W2072421347 modified "2023-10-17" @default.
• W2072421347 title "Interaction of 2-APB, dantrolene, and TDMT with IP3R and RyR modulates ER stress-induced programmed cell death I and II in neuron-like PC12 cells: an experimental and computational investigation" @default.
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• W2072421347 doi "https://doi.org/10.1080/07391102.2013.812520" @default.
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