Martin D.,Kings College London |
Li Y.,Kings College London |
Yang J.,Kings College London |
Wang G.,Xian Jiaotong University |
And 7 more authors.
Journal of Biological Chemistry | Year: 2014
It is well known that at herosclerosis occurs geographically at branch points where disturbed flow predisposes to the development of plaque via triggering of oxidative stress and inflammatory reactions. In this study, we found that disturbed flow activated antioxidative reactions via up-regulating heme oxygenase 1 (HO-1) in an X-box-binding protein 1 (XBP1) and histone deacetylase 3 (HDAC3)-dependent manner. Disturbed flow concomitantly up-regulated the unspliced XBP1 (XBP1u) and HDAC3 in a VEGFreceptor and PI3K/Akt-dependent manner. The presence of XBP1 was essential for the up-regulation of HDAC3 protein. Overexpression of XBP1u and/or HDAC3 activated Akt1 phosphorylation, Nrf2 protein stabilization and nuclear translocation, and HO-1 expression. Knockdown of XBP1u decreased the basal level and disturbed flow-induced Akt1 phosphorylation, Nrf2 stabilization, and HO-1 expression. Knockdown of HDAC3 ablated XBP1u-mediated effects. The mammalian target of rapamycin complex 2 (mTORC2) inhibitor, AZD2014, ablated XBP1u or HDAC3 or disturbed flow-mediated Akt1 phosphorylation, Nrf2 nuclear translocation, and HO-1 expression. Neither actinomycin D nor cycloheximide affected disturbed flow-induced up-regulation of Nrf2 protein. Knockdown of Nrf2 abolished XBP1u or HDAC3 or disturbed flow-induced HO-1 up-regulation. Co-immunoprecipitation assays demonstrated that XBP1u physically bound to HDAC3 and Akt1. The region of amino acids 201 to 323 of the HDAC3 protein was responsible for the binding to XBP1u. Double immunofluorescence staining revealed that the interactions between Akt1 and mTORC2, Akt1 and HDAC3, Akt1 and XBP1u, HDAC3, and XBP1u occurred in the cytosol. Thus, we demonstrate that XBP1u and HDAC3 exert a protective effect on disturbed flow-induced oxidative stress via up-regulation of mTORC2-dependent Akt1 phosphorylation and Nrf2-mediated HO-1 expression. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
Huang D.-H.,Huazhong University of Science and Technology |
Zhang S.-W.,Center Laboratory |
Zhao H.,Huazhong University of Science and Technology |
Zhang L.,Huazhong University of Science and Technology
Asian Journal of Andrology | Year: 2011
C-type natriuretic peptide (CNP) is a 22-amino acid peptide and act as a local paracrine or autocrine regulator. There is growing evidence that CNP is involved in male reproductive processes. To investigate the role of CNP during spermatogenesis, we measured the mRNA expression of CNP and its specific membrane-bound natriuretic peptide receptor-B (NPR-B) using real-time RT-PCR in the testes of normal rats on different postnatal days. After that spermatogenesis dysfunction model induced by ornidazole was established with the aim to study the correlation of CNP with spermatogenic dysfunction. Then, Sertoli cells from 18-to 22-day-old healthy male rats were cultured in the presence of different CNP concentrations (1×10-6, 1×10-7 and 1×10-8 moll-1), and the mRNA expression levels of androgen-binding protein, inhibin B and transferrin were examined at 0min, 30min, 1h, 2h, 4h, 8h, 12h, 24h and 48h. During the postnatal development of rat testes, the highest mRNA expression levels of CNP and NPR-B were found at postnatal D 0, and the levels then declined gradually, with a second CNP peak at postnatal D 35. In the ornidazole-induced infertile rat testes, CNP gene expression was lower than in the uninduced rats (P0.05), while NPR-B gene expression was greater (P0.05). In cultured Sertoli cells, supplementation with CNP stimulated the gene expression of androgen-binding protein/inhibin B/transferrin, particularly at 12h, and 1×10-7 mol l-1 CNP had the highest upregulation effect. The gene expression levels of CNP/NPR-B in rat testes at different postnatal stages and in infertile rat testes indicated that CNP may participate in the physiology and/or pathology related to spermatogenesis. Moreover, CNP regulated endocrine function in Sertoli cells. Taken together, these results showed that CNP is closely tied to spermatogenesis. © 2011 AJA, SIMM & SJTU. All rights reserved.
Kocabas H.,Konya Teaching and Research Hospital |
Kocabas V.,Center Laboratory |
Buyukbas S.,Selcuk University |
Melikoglu M.A.,Erzurum Teaching and Research Hospital |
And 2 more authors.
Rheumatology International | Year: 2012
Resistin is a recently described adipokine which is a member of cysteine-rich secretory protein family. Although it has been primarily defined in human adipocytes, it has been identified that its level was higher in mononuclear leukocytes, macrophages, spleen, and bone marrow cells. Because ankylosing spondylitis is an inflammatory disease, it is suspected that upregulation of proinflammatory cytokines is effective in its immunopathogenesis. The aim of our study is to determine the serum resistin levels in patients with AS and to research the relationship with disease activity markers. A total of 30 patients with AS and 30 healthy controls were included in this study. Serum resistin concentrations, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Bath AS Disease Activity Index (BASDAI) were evaluated. In results resistin levels in ankylosing spondylitis group were significantly higher than in control group. But, there was no correlation between resistin and ESR, CRP, BASDAI. In conclusion, higher serum resistin levels in patients with AS compared to healthy subjects give clues that resistin could have a role in the pathogenesis of AS. © Springer-Verlag 2010.
Su J.,Jiangsu Provincial Hospital of Traditional Chinese Medicine |
Yin L.P.,Jiangsu Provincial Hospital of Traditional Chinese Medicine |
Zhang X.,Jiangsu Provincial Hospital of Traditional Chinese Medicine |
Li B.B.,Jiangsu Provincial Hospital of Traditional Chinese Medicine |
And 2 more authors.
Transplantation Proceedings | Year: 2013
Aim In this study, we investigated the therapeutic efficacy and potential mechanisms of rhein to mitigate chronic allograft nephropathy (CAN) in rats. Materials and Methods Fisher rat donors and Lewis rat recipients were used to establish the CAN model. Thirty rats with transplanted kidneys were randomly divided into two groups: 16 untreated and 14 rhein = treated rats. Five Lewis rat controls underwent removal of their right kidneys. The Intervention group was administered rhein oral solution (100 mg kg-1 d-1) by gavage after transplantation. The untreated and control groups were given 0.5% sodium carboxymethyl cellulose. Blood and urine samples were collected at 4, 8, and 16 weeks to examine renal function and total urine protein. Half of the rats in each group were sacrifice at 8 or 16 weeks to examine renal pathology. Immunohistochemical examination and real-time polymerase chain reaction of renal tissues were performed to detect expressions of transforming growth-β1(TGF-β1), hepatic growth factor (HGF), bone morphogenetic protein 7 (BMP7), frobronectin, and collgen IV. Results Rhein improved renal function and significantly reduced renal fibrosis and interstitial inflammation. The levels of BMP7 and HGF were significantly elevated in the renal tissues of the rhein intervention group. In the meantime, fibronectin and collagen IV were decreased in the extracellular matrix. The expression of TGF-β1 was similar between these two groups. Conclusion Rhein improved renal function and reduced renal fibrosis and interstitial inflammation by inducing production of HGF and BMP7. © 2013 Elsevier Inc.
He Y.-J.,Xuzhou Medical College |
Wu J.-Z.,Center Laboratory |
Ji M.-H.,Jiangsu Cancer Hospital |
Ma T.,Nanjing Medical University |
And 3 more authors.
Experimental and Therapeutic Medicine | Year: 2013
Estrogen receptor-α (ERα) is essential for estrogen-dependent growth and its level of expression is a crucial determinant of response to endocrine therapy and prognosis in ERα-positive breast cancer. Breast cancer patients show a wide range of ERα expression levels which change in individual patients during disease progression and in response to systemic therapies. However, little is known concerning how the expression of ERα is regulated in human breast cancer. Recently, several microRNAs (miRNAs) have been identified to regulate ERα expression and to predict ER, progesterone receptor (PR) and human epidermal growth factor 2 (HER2) status. The expression levels of miR-342 and ERα mRNA were analyzed in human breast cancer samples and cell lines by quantitative reverse transcription (RT)-PCR analysis. The correlations between the expression levels of miR-342 and clinicopathological factors were analyzed. Statistically significant associations were observed between miR-342 and ER, HER2 and vascular endothelial growth factor (VEGF) status in the human breast cancer samples and the levels of miR-342 gradually increased as ERα mRNA expression increased. Moreover, ectopic overexpression of miR-342 upregulated the expression levels of the ERα mRNA and significantly sensitized the MCF-7 cells to tamoxifen-induced apoptosis and inhibition of cellular proliferation. These results suggested that miR-342 expression is positively correlated with ERα mRNA expression in human breast cancer and that it may be a significant marker for predicting tamoxifen sensitivity in ERα-positive breast cancer and a potential target for restoring ERα expression and responding to antiestrogen therapy.