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Huang Bao,He Yongqing,Li Shengwen,Wei Xiaoan,Liu Junhui,Shan Zhi,Huang Yue,Chen Jiang,Zhao Fengdong 생화학분자생물학회 2020 Experimental and molecular medicine Vol.52 No.-
Calcipressin-1, also known as regulator of calcineurin 1 (RCAN1), can specifically bind calcineurin at or near the calcineurin A catalytic domain and downregulate calcineurin activity. However, whether RCAN1 affects the hypoxic intervertebral disc (IVD) phenotype through the calcineurin/NFAT signaling pathway remains unclear. First, we confirmed the characteristics of the degenerative nucleus pulposus (NP) by H&E, safranin O/fast green and Alcian blue staining, and detected increased RCAN1 levels in the degenerative NP by immunohistochemistry. Then, we demonstrated that the protein level of RCAN1.4 was higher than that of RCAN1.1 and progressively elevated from the control group to the Pfirrmann grade V group. In vitro, both hypoxia (1% O2) and overexpression of HIF-1α reduced the protein level of RCAN1.4 in rat NP cells in a dose- and time-dependent manner. We further found that miRNA-124, through a nondegradative pathway (without the proteasome or lysosome), suppressed the expression of RCAN1.4. As expected, calcineurin in NP cells was activated and primarily promoted nuclear translocation of NFATc1 under hypoxia or RCAN1.4 siRNA transfection. Furthermore, SOX9, type II collagen and MMP13 were elevated under hypoxia, RCAN1.4 siRNA transfection or NFATc1 overexpression. Using chromatin immunoprecipitation (ChIP) and a luciferase reporter assay (with mutation), we clarified that NFATc1 increasingly bound the SOX9 promotor region (bp −367~−357). Interaction of HIF-1α and NFATc1 promoted MMP13 transcription. Finally, we found that FK506 reversed hypoxia-induced activation of the calcineurin/NFAT signaling pathway in NP cells and an ex vivo model. Together, these findings show that the RCAN1.4-calcineurin/ NFAT signaling pathway has a vital role in the hypoxic phenotype of NP cells. RCAN1.4 might be a therapeutic target for degenerative disc diseases.
Yue Meng,Shengjie Xia,Guoxiang Pan,Jilong Xue,Junhui Jiang,Zheming Ni 한국화학공학회 2017 Korean Journal of Chemical Engineering Vol.34 No.8
Copper(II) Schiff-base Complexes (Salen-Cu(II)) intercalated zinc-chromium layered double hydroxides (ZnSBCuCr-LDHs) were successfully prepared via coprecipitation. Then, a novel photocatalytic material Zn-Cu-Cr composite oxides (ZnSBCuCr-MO) was prepared after calcination at 500 oC with ZnSBCuCr-LDHs as precursor. The structure and properties of the materials were thoroughly characterized by powder X-ray diffraction (XRD), inductively coupled plasma atomic emission spectrometry (ICP-AES), ultraviolet visible diffuse reflectance spectroscopy (UV-Vis DRS), scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). The photocatalytic activities of the materials were investigated by photodegradation of a cationic dye Rhodamin B (RhB), which was hard to adsorb by LDHs. The effects of the photocatalyst dosage, the initial pH and temperature of RhB solution on the photocatalytic efficiency were discussed. The results showed that ZnSBCuCr-MO displayed higher photocatalytic activity for RhB than calcined ZnCr-LDHs (ZnCr-MO) and calcined ZnCuCr-LDHs (ZnCuCr-MO). Meanwhile, ZnSBCuCr- MO exhibited better stability and reusability. In addition, the possible photocatalytic mechanism and degradation pathway for RhB were studied through density functional theory (DFT) calculation of the RhB molecule, UV-vis absorption variation and LC-MS analyses of the RhB solution.