Store-operated Ca2+ entry(SOCE) controls intracellular Ca2+ homeostasis and regulates a wide range of cellular events including proliferation,migration and invasion.The discovery of STIM proteins as Ca2+ sensors and O...Store-operated Ca2+ entry(SOCE) controls intracellular Ca2+ homeostasis and regulates a wide range of cellular events including proliferation,migration and invasion.The discovery of STIM proteins as Ca2+ sensors and Orai proteins as Ca2+ channel pore forming units provided molecular tools to understand the physiological function of SOCE.Many studies have revealed the pathophysiological roles of Orai and STIM in tumor cells.This review focuses on recent advances in SOCE and its contribution to tumorigenesis.Altered Orai and/or STIM functions may serve as biomarkers for cancer prognosis,and targeting the SOCE pathway may provide a novel means for cancer treatment.展开更多
OBJECTIVE:To determine the effect of Wenyang Huazhuo Fang(WHF),a Traditional Chinese Medicine decoction,on renal function in a rat model of doxorubicin-induced nephropathy,and to elucidate the underlying mechanism.MET...OBJECTIVE:To determine the effect of Wenyang Huazhuo Fang(WHF),a Traditional Chinese Medicine decoction,on renal function in a rat model of doxorubicin-induced nephropathy,and to elucidate the underlying mechanism.METHODS:Sprague-Dawley rats were randomly divided into six groups:control,doxorubicin-nephropathy,and prednisone-treated(6.45 mg·kg^-1·d^-1)doxorubicin nephropathy groups,as well as high-(7.26 g·kg^-1·d^-1),medium-(2.42 g·kg-1·d-),and low-dose(0.81 g·kg^-1·d^-1)WHF-treated doxorubicin-nephropathy groups.The nephropathy rat model was established by two tail vein injections of doxorubicin,followed by prednisone or WHF treatment for 8 weeks.Body weights were monitored and urinary protein was measured every 2 weeks.After the end of the treatment period,the rats were euthanized.Serum biochemical indicators were determined and renal morphological alterations were assessed using histological staining.The expression of transient receptor potential cation channel subfamily C member 6(TRPC6),stromal interaction molecule 1(STIM1),and calcium release-activated calcium channel protein 1(Orai1)was detected using western blotting,and their mRNA levels were examined using quantitative real-time reverse transcription-polymerase chain reaction.RESULTS:WHF treatment was found to significantly ameliorate weight loss,proteinuria,hypoalbuminemia,and dyslipidemia in doxorubicin-nephropathy rats.The protein and mRNA levels of TRPC6,STIM1,and Orai1 were partially,but significantly suppressed by prednisone or WHF treatment.CONCLUSION:Treatment with WHF significantly ameliorates renal injury in a rat model of doxorubicin-induced nephropathy,which could be at least partially related to repression of the TRPC6 pathway.展开更多
文摘Store-operated Ca2+ entry(SOCE) controls intracellular Ca2+ homeostasis and regulates a wide range of cellular events including proliferation,migration and invasion.The discovery of STIM proteins as Ca2+ sensors and Orai proteins as Ca2+ channel pore forming units provided molecular tools to understand the physiological function of SOCE.Many studies have revealed the pathophysiological roles of Orai and STIM in tumor cells.This review focuses on recent advances in SOCE and its contribution to tumorigenesis.Altered Orai and/or STIM functions may serve as biomarkers for cancer prognosis,and targeting the SOCE pathway may provide a novel means for cancer treatment.
基金grants from Knowlodge Innovation Projectof The Chinese Academy of Sciences(KSCX2-SW- 224, Y2004018)National Basic Research Program of China(2004CB720000)~~
基金the Key Research and Development Projects of Shaanxi Province(Study on the Effect of Wenyanghuazhuo Method on Autophagy-related Proteins in Adriamycin Nephropathy Rat Model,No.2020SF-340)a Grant from the Sci-tech Project of Shaanxi Province(Study on the Expression Regulation of STIM1/Orail and TRPC-related Channel Proteins in Renal Tissues of Adriamycin Nephropathy Rats by Aconiti Lateralis Radix and Wenyanghuazhuofang,No.2016SF-068)。
文摘OBJECTIVE:To determine the effect of Wenyang Huazhuo Fang(WHF),a Traditional Chinese Medicine decoction,on renal function in a rat model of doxorubicin-induced nephropathy,and to elucidate the underlying mechanism.METHODS:Sprague-Dawley rats were randomly divided into six groups:control,doxorubicin-nephropathy,and prednisone-treated(6.45 mg·kg^-1·d^-1)doxorubicin nephropathy groups,as well as high-(7.26 g·kg^-1·d^-1),medium-(2.42 g·kg-1·d-),and low-dose(0.81 g·kg^-1·d^-1)WHF-treated doxorubicin-nephropathy groups.The nephropathy rat model was established by two tail vein injections of doxorubicin,followed by prednisone or WHF treatment for 8 weeks.Body weights were monitored and urinary protein was measured every 2 weeks.After the end of the treatment period,the rats were euthanized.Serum biochemical indicators were determined and renal morphological alterations were assessed using histological staining.The expression of transient receptor potential cation channel subfamily C member 6(TRPC6),stromal interaction molecule 1(STIM1),and calcium release-activated calcium channel protein 1(Orai1)was detected using western blotting,and their mRNA levels were examined using quantitative real-time reverse transcription-polymerase chain reaction.RESULTS:WHF treatment was found to significantly ameliorate weight loss,proteinuria,hypoalbuminemia,and dyslipidemia in doxorubicin-nephropathy rats.The protein and mRNA levels of TRPC6,STIM1,and Orai1 were partially,but significantly suppressed by prednisone or WHF treatment.CONCLUSION:Treatment with WHF significantly ameliorates renal injury in a rat model of doxorubicin-induced nephropathy,which could be at least partially related to repression of the TRPC6 pathway.
