The First Cellular Step for Chemotherapy Induced Peripheral Neuropathy After Vincristine Treatment May Require Binding to Neuronal Calcium Sensor‐ 1

• DOI: 10.1096/fasebj.30.1_supplement.969.3
• Publication Date: 2023-11-26T16:23:51Z
• Authors: Elisa Viveros Araque; Larry Huynh; Lien Nguyen; Yifei Yang; Juliana Rengifo; Barbara Ehrich
• Keywords: Valproic Acid; Calcium in biology

Many chemotherapy drugs induce peripheral neuropathy (PN), a painful and irreversible side effect. Previous results reported in the literature show that Paclitaxel vincristine, which are anti-microtubule targeting drugs, PN by mechanisms not fully understood. The Ehrlich group has neuronal cell line primary rat dorsal root ganglia, paclitaxel binds to protein calcium sensor-1 (NCS-1) triggers calpain-dependent decrease intracellular signaling via degradation of NCS-1 subsequent dependent inositol trisphosphate receptor release. Other groups have previously disturbed PN. Similar effects also been with vincristine. On other hand, there reports showing pretreatment valproic acid prevents development when it is administered cisplatin, drug. We hypothesized vincristine bind produce their using same cellular cascade as paclitaxel. Specifically our hypothesis was processes while blocks initiated alterations associated expressed recombinantly prokaryotic system. After induction expression, extracted purified hydrophobic interaction chromatography, desalting, dialysis. Interactions between both were measured isothermal titration calorimetry (ITC). First, binding monitored NCS-1-calcium matched published reports. Using ITC, we did observe any reaction Valproic under calcium-free calcium-saturating conditions. In ITC study or without calcium, observed appeared NCS-1. However, conclusive if such heat changes result NCS-1, reason addition alters pH buffer this can create variations results. Our suggest protective do involve direct probably involves pathways. treatment does These important for understanding mechanism induced finding possible drug targets Support Funding Information Acknowledgments: I thank American Physiological Society, Yale University Universidad Icesi economic academic support made realization research project. test ITC. A) Positive control 139 uM, Calcium chloride (CaCl2) 5 mM, T: 28°C, pH: 7,2 Ca+2. B) NCS-1: 139uM plus 5mM CaCl2 (VA) 6mM mM CaCl2, T:28°C, 7,3 VA bind. C) ) 100uM (VC) 10mM, 7,3. There may be VC. D) VC 4mM 6,6.