Resveratrol reduces store-operated Ca2+ entry and enhances the apoptosis of fibroblast-like synoviocytes in adjuvant arthritis rats model via targeting ORAI1-STIM1 complex

Abstract Background: Resveratrol was reported to trigger the apoptosis of fibroblast-like synoviocytes In adjuvant arthritis rats but the subcellular mechanism remains unclear. Since ER stress, mitochondrial dysfunction and oxidative stress were involved in the effects of resveratrol with imbalance...

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Autores principales: Lu,Jinsen, Yang,Jiazhao, Zheng,Yongshun, Fang,Shiyuan, Chen,Xiaoyu
Lenguaje:English
Publicado: Sociedad de Biología de Chile 2019
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Acceso en línea:http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602019000100242
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spelling oai:scielo:S0716-976020190001002422019-10-10Resveratrol reduces store-operated Ca2+ entry and enhances the apoptosis of fibroblast-like synoviocytes in adjuvant arthritis rats model via targeting ORAI1-STIM1 complexLu,JinsenYang,JiazhaoZheng,YongshunFang,ShiyuanChen,Xiaoyu Resveratrol Apoptosis Store-operated calcium entry STIM1 ORAI1 Abstract Background: Resveratrol was reported to trigger the apoptosis of fibroblast-like synoviocytes In adjuvant arthritis rats but the subcellular mechanism remains unclear. Since ER stress, mitochondrial dysfunction and oxidative stress were involved in the effects of resveratrol with imbalance of calcium bio-transmission, store operated calcium entry (SOCE), a novel intracellular calcium regulatory pathway, may also participate in this process. Results: In the present study, Resveratrol was found to suppress ORAI1 expression of a dose dependent manner while have no evident effects on STIM1 expressive level. Besides, resveratrol had no effects on ATP or TG induced calcium depletion but present partly dose-dependent suppression of SOCE. On the one hand, microinjection of ORAI1 overexpressed vector in sick toe partly counteracted the therapeutic effects of resveratrol on adjuvant arthritis and serum inflammatory cytokine including IL-1, IL-6, IL-8, IL-10 and TNF-α. On the other hand, ORAI1 SiRNA injection provided slight relief to adjuvant arthritis in rats. In addition, ORAI1 overexpression partly diminished the alleviation of hemogram abnormality induced by adjuvant arthritis after resveratrol treatment while ORAI1 knockdown presented mild resveratrol-like effect on hemogram in rats model. Conclusion: These results indicated that resveratrol reduced store-operated Ca2+ entry and enhanced the apoptosis of fibroblast-like synoviocytes in adjuvant arthritis rats model via targeting ORAI1-STIM1 complex, providing a theoretical basis for ORAI1 targeted therapy in future treatment with resveratrol on rheumatoid arthritis.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.52 20192019-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602019000100242en10.1186/s40659-019-0250-7
institution Scielo Chile
collection Scielo Chile
language English
topic Resveratrol
Apoptosis
Store-operated calcium entry
STIM1
ORAI1
spellingShingle Resveratrol
Apoptosis
Store-operated calcium entry
STIM1
ORAI1
Lu,Jinsen
Yang,Jiazhao
Zheng,Yongshun
Fang,Shiyuan
Chen,Xiaoyu
Resveratrol reduces store-operated Ca2+ entry and enhances the apoptosis of fibroblast-like synoviocytes in adjuvant arthritis rats model via targeting ORAI1-STIM1 complex
description Abstract Background: Resveratrol was reported to trigger the apoptosis of fibroblast-like synoviocytes In adjuvant arthritis rats but the subcellular mechanism remains unclear. Since ER stress, mitochondrial dysfunction and oxidative stress were involved in the effects of resveratrol with imbalance of calcium bio-transmission, store operated calcium entry (SOCE), a novel intracellular calcium regulatory pathway, may also participate in this process. Results: In the present study, Resveratrol was found to suppress ORAI1 expression of a dose dependent manner while have no evident effects on STIM1 expressive level. Besides, resveratrol had no effects on ATP or TG induced calcium depletion but present partly dose-dependent suppression of SOCE. On the one hand, microinjection of ORAI1 overexpressed vector in sick toe partly counteracted the therapeutic effects of resveratrol on adjuvant arthritis and serum inflammatory cytokine including IL-1, IL-6, IL-8, IL-10 and TNF-α. On the other hand, ORAI1 SiRNA injection provided slight relief to adjuvant arthritis in rats. In addition, ORAI1 overexpression partly diminished the alleviation of hemogram abnormality induced by adjuvant arthritis after resveratrol treatment while ORAI1 knockdown presented mild resveratrol-like effect on hemogram in rats model. Conclusion: These results indicated that resveratrol reduced store-operated Ca2+ entry and enhanced the apoptosis of fibroblast-like synoviocytes in adjuvant arthritis rats model via targeting ORAI1-STIM1 complex, providing a theoretical basis for ORAI1 targeted therapy in future treatment with resveratrol on rheumatoid arthritis.
author Lu,Jinsen
Yang,Jiazhao
Zheng,Yongshun
Fang,Shiyuan
Chen,Xiaoyu
author_facet Lu,Jinsen
Yang,Jiazhao
Zheng,Yongshun
Fang,Shiyuan
Chen,Xiaoyu
author_sort Lu,Jinsen
title Resveratrol reduces store-operated Ca2+ entry and enhances the apoptosis of fibroblast-like synoviocytes in adjuvant arthritis rats model via targeting ORAI1-STIM1 complex
title_short Resveratrol reduces store-operated Ca2+ entry and enhances the apoptosis of fibroblast-like synoviocytes in adjuvant arthritis rats model via targeting ORAI1-STIM1 complex
title_full Resveratrol reduces store-operated Ca2+ entry and enhances the apoptosis of fibroblast-like synoviocytes in adjuvant arthritis rats model via targeting ORAI1-STIM1 complex
title_fullStr Resveratrol reduces store-operated Ca2+ entry and enhances the apoptosis of fibroblast-like synoviocytes in adjuvant arthritis rats model via targeting ORAI1-STIM1 complex
title_full_unstemmed Resveratrol reduces store-operated Ca2+ entry and enhances the apoptosis of fibroblast-like synoviocytes in adjuvant arthritis rats model via targeting ORAI1-STIM1 complex
title_sort resveratrol reduces store-operated ca2+ entry and enhances the apoptosis of fibroblast-like synoviocytes in adjuvant arthritis rats model via targeting orai1-stim1 complex
publisher Sociedad de Biología de Chile
publishDate 2019
url http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602019000100242
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AT yangjiazhao resveratrolreducesstoreoperatedca2entryandenhancestheapoptosisoffibroblastlikesynoviocytesinadjuvantarthritisratsmodelviatargetingorai1stim1complex
AT zhengyongshun resveratrolreducesstoreoperatedca2entryandenhancestheapoptosisoffibroblastlikesynoviocytesinadjuvantarthritisratsmodelviatargetingorai1stim1complex
AT fangshiyuan resveratrolreducesstoreoperatedca2entryandenhancestheapoptosisoffibroblastlikesynoviocytesinadjuvantarthritisratsmodelviatargetingorai1stim1complex
AT chenxiaoyu resveratrolreducesstoreoperatedca2entryandenhancestheapoptosisoffibroblastlikesynoviocytesinadjuvantarthritisratsmodelviatargetingorai1stim1complex
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