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目的 探讨特立帕肽对高糖微环境下小鼠胚胎成骨细胞(MC3T3-E1)分化的影响及作用机制。方法 将MC3T3-E1细胞分为正常糖组(NG,5.5 mmol/L葡萄糖)、NG+特立帕肽组(5.5 mmol/L葡萄糖+10 nmol/L特立帕肽)、高糖组(HG,25 mmol/L葡萄糖)、HG+特立帕肽组(25 mmol/L葡萄糖+10 nmol/L特立帕肽)和HG+特立帕肽+PKA抑制剂组(25 mmol/L葡萄糖+10 nmol/L特立帕肽+20 μmol/L H-89)。CCK-8法检测细胞增殖;ELISA实验检测各组cAMP水平;试剂盒检测碱性磷酸酶(ALP)活性;茜素红染色检测细胞矿化结节生成情况;鬼笔环肽染色后观察细胞骨架;Real-time PCR检测细胞中PKA、CREB、RUNX2和Osx的mRNA表达水平。结果 各组细胞增殖能力差异无统计学意义(P>0.05)。与NG组相比,NG+特立帕肽组细胞cAMP水平升高(P<0.05),ALP活性增强(P<0.05),茜素红矿化结节生成能力增强(P<0.05),细胞骨架清晰程度有所提升,PKA、CREB、RUNX2和Osx的mRNA表达上调(P<0.05);与NG组相比,HG组的上述检测结果则呈减弱趋势。与HG组相比,HG+特立帕肽组细胞cAMP水平上升(P<0.05),ALP活性增强(P<0.05),茜素红矿化结节生成能力增强(P<0.05),细胞骨架清晰程度有所提升,PKA、CREB、RUNX2和Osx的mRNA表达上调(P<0.05)。与HG+特立帕肽组相比,HG+特立帕肽+H-89组细胞cAMP水平下降(P<0.05),ALP活性减弱(P<0.05),茜素红矿化结节生成能力减弱(P<0.05),细胞骨架清晰程度下降,PKA、CREB、RUNX2和Osx的mRNA表达下调(P<0.05)。结论 特立帕肽可通过激活cAMP/PKA/CREB信号通路有效改善高糖微环境对MC3T3-E1细胞分化的抑制作用。 相似文献
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c AMP反应成分结合蛋白 (c AMP response elem ent-binding protein,CREB)是一种转录因子 ,它在磷酸化之后可调节靶基因的转录。 CREB在 13 3位置的丝氨酸的磷酸化 ,与脊髓中伤害性传入的处理有关 ,本文作者等用特殊抗体对此进行了免疫细胞化学研究。在正常大鼠 ,虽然几乎所有脊髓神经元的核中都可见 CREB的轻度着色 ,但磷酸化的 CREB仅见于双侧腰段脊髓的 ~ 层 (75± 15 vs60± 18)和 层 (9± 3 )。用福尔马林注射引起一侧后脚掌出现炎症时 ,可在双侧腰段脊髓看到磷酸化CREB细胞核的快速 (小于 5 min)和节段性的显著增多 ;它们主要分布在双侧背角表层 ~ 层 (2 5 4± 2 0 vs 2 62± 2 3 )、 层(115± 13 )和双侧 ~ 层 (3 46± 2 0 vs3 2 8± 2 6) ;而在对照和炎症组大鼠的胸段脊髓中均未见磷酸化 CREB的增加。在注射CFA诱发一侧炎症或切断一侧坐骨神经的实验组大鼠 ,也可看到至少延续到第三天的强而双侧性的 CREB的磷酸化。这种由一侧后肢伤害性传入引致腰段脊髓中镜像式双侧 CREB磷酸化的出现 ,与一般看到的损伤传入只在同侧脊髓背角引起某些神经化学改变的结果不同 ,可能是人神经损伤后或在实验动物中出现对侧镜像式疼痛过敏现象的基础 相似文献
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NGF对局灶性脑缺血再灌注大鼠海马CREB表达的上调作用 总被引:1,自引:0,他引:1
目的探讨外源性神经生长因子(NGF)对局灶性脑缺血再灌注大鼠海马CREB和磷酸化的CREB(p-CREB)表达的影响。方法用线栓法阻塞大鼠大脑中动脉制作局灶性脑缺血再灌注模型,应用免疫组织化学、W estern B loting和图像分析方法检测大鼠海马CA1区CREB和磷酸化CREB表达。结果假手术组海马CA1区CREB有明显表达,缺血再灌注组CA1区表达较假手术组减少,NGF组CA1区的CREB表达多于缺血再灌注组(P<0.05)。假手术组海马CA1区p-CREB表达很少,缺血再灌注组p-CREB表达多于假手术组,NGF组p-CREB表达多于缺血再灌注组(P<0.05)。结论NGF上调海马CREB和p-CREB的表达,对缺血神经元起保护作用,CREB和p-CREB参与NGF对缺血神经元的保护作用机制。 相似文献
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Wen Jie Tian Seung Hwan Jeon Guan Qun Zhu Eun Bi Kwon Ga Eun Kim Woong Jin Bae Hyuk Jin Cho U-Syn Ha Sung-Hoo Hong Ji Youl Lee Kang Sup Kim Sae Woong Kim 《Translational andrology and urology》2021,10(1):345
BackgroundThe purpose of this study is to explore the effects of high-BDNF microenvironment produced by engineered immortalized mesenchymal stem cells (imMSCs) on the neurogenic bladder (NB) and investigate underlying mechanism.MethodsMale Sprague-Dawley rat (12-week-old, weighing about 370–400 g) were purchased from a Korean company (Orient Bio Co. Seongnam, Korea) and divided into the following groups (n=32): sham control group (n=8), NB group (n=8), NB + ImMSCs group (n=8), NB + ImMSCs (BDNF) group (n=8). The major pelvic ganglion (MPG) was observed under anesthesia. Three NB groups of rats were then subjected to bilateral MPG injury. The sham control group of rats was treated with sham surgery. Cystometry were performed before the rats were sacrificed, and then MPG and bladder were collected for histochemical and Western blot analysis.ResultsMSCs treatment improves lower urinary tract function, and the NB + ImMSCs (BDNF) group is better than the NB + ImMSCs group (P<0.01). MSCs treatment accelerates recovery of injured nerve tissue, and the NB + ImMSCs (BDNF) group is better than the NB + ImMSCs group (P<0.01). In high BDNF environment, apoptosis was reduced more significantly and muscle tissue recovered more rapidly (P<0.01). High-BDNF microenvironment activates more BDNF/TrkB/CREB signaling pathways (P<0.01).ConclusionsIn a rat NB model caused by nerve injury, imMSCs have certain effects on nerve tissue repair. At the same time, it was proved that increasing the expression of BDNF which had specific effect on nerve injury repair could more effectively repair injured MPG in local microenvironment. The mechanism may be related to the activation of the BDNF/TrkB/CREB signaling pathway and the reduction of apoptosis by highly expressed BDNF. 相似文献
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SooHyun Kim Zsuzsanna Barad Rachel Y. Cheong Istvn M. brahm 《Journal of neuroendocrinology》2020,32(1)
Rapid nonclassical effects of 17β‐oestradiol (E2) on intracellular signalling have been identified in the basal forebrain, although the extent to which these actions may be different in males and females is unknown. Previous work has shown that E2 rapidly phosphorylates cAMP responsive element binding protein (CREB) via ΕRα in female cholinergic neurones. Using this indicator, the present study examined whether nonclassical actions of E2 occur in a sexually dimorphic manner within basal forebrain cholinergic neurones in mice. In addition, we investigated the expression and intracellular distribution of oestrogen receptor (ΕR)α in cholinergic neurones in female and male mice. Animals were gonadectomised and treated 2 weeks later with E2. The number of CREB‐expressing cholinergic neurones was not altered in any of the brain regions after E2 treatment in both males and females. However, E2 treatment rapidly (< 15 minutes) increased (P < 0.05) the number of cholinergic neurones expressing phosphorylated CREB (pCREB) in the substantia innominata and medial septum but not in the striatum in female mice. By contrast, E2 did not change pCREB expression in cholinergic neurones in male mice at any time point (15 minutes, 1 hour, 4 hours), irrespective of the neuroanatomical location. We also observed that, in females, more cholinergic neurones expressed nuclear ΕRα in all regions, whereas males showed more cholinergic neurones with cytoplasmic or both nuclear and cytoplasmic expression of ΕRα. Taken together, these results demonstrate a marked sex difference in the E2‐induced nonclassical effect and intracellular distribution of ΕRα in basal forebrain cholinergic neurones in vivo. 相似文献
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Jan Detka Joanna Ślusarczyk Anna Kurek Mateusz Kucharczyk Tomasz Adamus Paweł Konieczny Marta Kubera Agnieszka Basta-Kaim Władysław Lasoń Bogusława Budziszewska 《Pharmacological reports : PR》2019,71(2):338-346