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Resveratrol reduces store-operated Ca2+ entry and enhances the apoptosis of fibroblast-like synoviocytes in adjuvant arthritis rats model via targeting ORAI1-STIM1 complex
Lu, Jinsen; Yang, Jiazhao; Zheng, Yongshun; Fang, Shiyuan; Chen, Xiaoyu.
  • Lu, Jinsen; Anhui Medical University. Anhui Provincial Hospital. Department of Orthopaedics. Anhui. CN
  • Yang, Jiazhao; Anhui Medical University. Anhui Provincial Hospital. Department of Orthopaedics. Anhui. CN
  • Zheng, Yongshun; Anhui Medical University. Anhui Provincial Hospital. Department of Orthopaedics. Anhui. CN
  • Fang, Shiyuan; Anhui Medical University. Anhui Provincial Hospital. Department of Orthopaedics. Anhui. CN
  • Chen, Xiaoyu; Anhui Medical University. Department of Histology and Embryology. Hefei. CN
Biol. Res ; 52: 45, 2019. tab, graf
Article in English | LILACS | ID: biblio-1019509
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.
Subject(s)


Full text: Available Index: LILACS (Americas) Main subject: Arthritis, Experimental / Calcium Channels / Apoptosis / Fibroblasts / Synoviocytes / Stromal Interaction Molecule 1 / ORAI1 Protein / Resveratrol Limits: Animals Language: English Journal: Biol. Res Journal subject: Biology Year: 2019 Type: Article Affiliation country: China Institution/Affiliation country: Anhui Medical University/CN

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Full text: Available Index: LILACS (Americas) Main subject: Arthritis, Experimental / Calcium Channels / Apoptosis / Fibroblasts / Synoviocytes / Stromal Interaction Molecule 1 / ORAI1 Protein / Resveratrol Limits: Animals Language: English Journal: Biol. Res Journal subject: Biology Year: 2019 Type: Article Affiliation country: China Institution/Affiliation country: Anhui Medical University/CN