國家衛生研究院 NHRI:Item 3990099045/12262
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    題名: Cathepsin S inhibition alleviates oxaliplatin-induced peripheral neuropathy through regulation of Ca2+homeostasis
    作者: Chen, SJ;Shen, MR;Chen, LH;Lin, HH;Hsu, SH;Chang, JY
    貢獻者: National Institute of Cancer Research
    摘要: Chemotherapeutic drug oxaliplatin is frequently causing chemotherapy-induced peripheral neuropathy. Currently, there is no effective drug to prevent neuropathy in the clinic. Therefore, identification of the potential target to treat to alleviate oxaliplatin-induced neuropathy is urgent. Previously, the release of cathepsin S (CTSS) from microglial cells, which causes neuropathic pain, has been reported, but the detailed mechanism remains unclear. In this study, we discovered that oxaliplatin treatment triggers CTSS expression accompanies with prompted calcium influx from SOCE in vitro. And, the oxaliplatin treated mice displayed increased tail-withdrawal temperature hyperalgesia and impaired locomotor activity along with the loss of neuromuscular function. Furthermore, oxaliplatin-induced peripheral neuropathy was inhibited by the highly selective CTSS inhibitor, 58, which significantly improved the thermal sensitivity and alleviated mechanical allodynia on the heat tail-withdrawal and von Frey tests in oxaliplatin-treated mice, respectively. The grip strength test showed that 58 significantly improved the motor strength and neuromuscular function of oxaliplatin-treated mice. The ultrastructure of sciatic nerve myelin integrity through G ratio quantification supported the observations in our oxaliplatin-induced peripheral neuropathy mouse behavioral tests. Also, inhibition of CTSS enzymatic activity by 58 resulted in the suppression of STIM1 aggregation and decreasing the oxaliplatin-induced calcium influx from SOCE. These results revel a novel molecular mechanism of CTSS in the involvement of oxaliplatin-induced peripheral neuropathy.
    日期: 2019-07
    關聯: Cancer Research. 2019 Jul;79(13, Suppl.):Abstract number 2942.
    Link to: http://dx.doi.org/10.1158/1538-7445.Sabcs18-2942
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0008-5472&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000488279401390
    顯示於類別:[張俊彥] 會議論文/會議摘要

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