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991.
Zixian Chen Zheng Li Chang Jiang Xiaoxing Jiang Jian Zhang 《Journal of cellular physiology》2019,234(12):23043-23052
Emerging evidence indicates that microRNAs play an important role in neural remodeling, including neurite growth, after acute spinal cord injury (ASCI). This study aims to identify the mechanism by which miR-92b-3p regulates neurite growth in vivo and in vitro. Adult Sprague–Dawley rats were selected to establish the ASCI model, and the expressions of miR-92b-3p and phosphate and tensin homolog deleted on chromosome ten (PTEN) were quantified at different time points. The interaction between miR-92b-3p and PTEN was further detected in the PC12 cell line and dual-luciferase reporter assay. Neurite growth proteins (GAP43 and NF-200) were assessed by western blotting after miR-92b-3p mimics treatment. The PTEN/AKT pathway-related proteins and their roles in miR-92b-3p regulation were also identified using western blotting and immunofluorescence in vitro through LY294002, an AKT inhibitor. The effect of miR-92b-3p was further determined in vivo according to the Basso-Beattie-Bresnahan (BBB) Scale and GAP43 and NF-200 expressions. miR-92b-3p was downregulated after ASCI, while PTEN showed a simultaneous opposing trend. Overexpression of miR-92b-3p downregulated PTEN expression and promoted phosphorylation of AKT, as well as the expression of GAP43 and NF-200 in PC12 cells. Furthermore, the dual-luciferase reporter assay revealed that miR-92b-3p exerted its effect by targeting PTEN's 3ʹ-untranslated regions and that this effect could be counteracted by AKT phosphorylation blocker LY294002 through western blotting and immunofluorescence. Moreover, miR-92b-3p could also improve the BBB scale as well as GAP43 and NF-200 expression levels in vivo. Collectively, these results indicate that miR-92b-3p promotes neurite growth and functional recovery through the PTEN/AKT pathway in ASCI. 相似文献
992.
Ye Yuan Yong-yi Wang Xin Liu Bin Luo Lei Zhang Fei Zheng Xing-Yuan Li Ling-Yun Guo Lu Wang Miao Jiang Ya-mu Pan Yu-wen Yan Jian-ye Yang Shi-You Chen Jia-Ning Wang Jun-Ming Tang 《Journal of cellular physiology》2019,234(12):22921-22934
Bax triggers cell apoptosis by permeabilizing the outer mitochondrial membrane, leading to membrane potential loss and cytochrome c release. However, it is unclear if proteasomal degradation of Bax is involved in the apoptotic process, especially in heart ischemia-reperfusion (I/R)-induced injury. In the present study, KPC1 expression was heightened in left ventricular cardiomyocytes of patients with coronary heart disease (CHD), in I/R-myocardium in vivo and in hypoxia and reoxygenation (H/R)-induced cardiomyocytes in vitro. Overexpression of KPC1 reduced infarction size and cell apoptosis in I/R rat hearts. Similarly, the forced expression of KPC1 restored mitochondrial membrane potential (MMP) and cytochrome c release driven by H/R in H9c2 cells, whereas reducing cell apoptosis, and knockdown of KPC1 by short-hairpin RNA (shRNA) deteriorated cell apoptosis induced by H/R. Mechanistically, forced expression of KPC1 promoted Bax protein degradation, which was abolished by proteasome inhibitor MG132, suggesting that KPC1 promoted proteasomal degradation of Bax. Furthermore, KPC1 prevented basal and apoptotic stress-induced Bax translocation to mitochondria. Bax can be a novel target for the antiapoptotic effects of KPC1 on I/R-induced cardiomyocyte apoptosis and render mechanistic penetration into at least a subset of the mitochondrial effects of KPC1. 相似文献
993.
Xia Zhao Zhiwen Zeng Uma Gaur Jiankang Fang Tangming Peng Shuai Li Wenhua Zheng 《Journal of cellular physiology》2019,234(9):16619-16629
Metformin, a first line anti type 2 diabetes drug, has recently been shown to extend lifespan in various species, and therefore, became the first antiaging drug in clinical trial. Oxidative stress due to excess reactive oxygen species (ROS) is considered to be an important factor in aging and related disease, such as Alzheimer's disease (AD). However, the antioxidative effects of metformin and its underlying mechanisms in neuronal cells is not known. In the present study, we showed that metformin, in clinically relevant concentrations, protected neuronal PC12 cells from H2O2-induced cell death. Metformin significantly ameliorated cell death due to H2O2 insult by restoring abnormal changes in nuclear morphology, intracellular ROS, lactate dehydrogenase, and mitochondrial membrane potential induced by H2O2. Hoechst staining assay and flow cytometry analysis revealed that metformin significantly reduced the apoptosis in PC12 cells exposed to H2O2. Western blot analysis further demonstrated that metformin stimulated the phosphorylation and activation of AMP-activated protein kinase (AMPK) in PC12 cells, while application of AMPK inhibitor compound C, or knockdown of the expression of AMPK by specific small interfering RNA or short hairpin RNA blocked the protective effect of metformin. Similar results were obtained in primary cultured hippocampal neurons. Taken together, these results indicated that metformin is able to protect neuronal cells from oxidative injury, at least in part, via the activation of AMPK. As metformin is comparatively cheaper with much less side effects in clinic, our findings support its potential to be a drug for prevention and treatment of aging and aging-related diseases. 相似文献
994.
Xiaojing Xia Xin Wang Yi Zheng Jinqing Jiang Jianhe Hu 《Journal of cellular physiology》2019,234(6):7885-7892
Pyroptosis, a type of programmed cell death mediated by gasdermin, is characterized by the swelling and rupture of cells, release of cellular contents and a strong inflammatory response, which is critical for controlling microbial infection. Pattern recognition receptors recognize the intracellular and extracellular pathogenic microbial components and stimulate the organism's inflammatory response by activating the pyroptosis signaling pathway and releasing interleukin-1β (IL-1β), IL-18, and other inflammatory factors to promote pathogen clearance and prevent infection. In the process of continuous evolution, pathogens have developed multiple strategies to modulate the occurrence of pyroptosis and thus enhance their ability to induce disease; that is, the competition between host cells and pathogens controls the occurrence of pyroptosis. Competition can directly affect tissue inflammation outbreaks and even alter cell survival. Studies have shown that various bacterial infections, including Shigella flexneri, Salmonella, Listeria monocytogenes, and Legionella pneumophila, can lead to pyroptosis. Pyroptosis is associated with the occurrence and development of various diseases caused by microbial infection, and the identification of molecules related to the pyroptosis signaling pathway may provide new drug targets for the treatment of related diseases. This study reviews the molecular mechanisms of pyroptosis and the role of pyroptosis in microbial infection-related diseases. 相似文献
995.
Ning Sheng Yanyan Wang Ying Xie Sihan Chen Jun Lu Zifeng Zhang Mengqiu Li Qun Shan Dongmei Wu Guihong Zheng Yuanlin Zheng Shaohua Fan 《Journal of cellular physiology》2019,234(8):13001-13013
Homo sapiens longevity assurance homolog 2 of yeast LAG1 (LASS2), is a gene isolated from a human liver complementary DNA library. In this study, we found that LASS2 protein level was positively related to International Federation of Gynecology and Obstetrics (FIGO) stage and LASS2-negative tumors showed significant association with longer disease-free survival (DFS) and overall survival (OS) in ovarian cancer patients. The heterogeneous expression of LASS2 had been exhibited in diverse ovarian cancer cells. A significantly lower messenger RNA (mRNA) and protein level of LASS2 was seen in 3AO cell compared with those in other types of ovarian cancer cells. Meanwhile, the mRNA and protein levels of LASS2 in ES-2 and NIH:OVCAR-3 cells were obviously higher. LASS2 overexpression in 3AO cell could promote migration, invasion, and metastasis abilities in vitro and in vivo, while LASS2 knockdown in ES-2 and NIH:OVCAR-3 cells had the opposite effects. The oncogenic capacity of LASS2 in ovarian cancer may be mediated by increased expression of YAP/TAZ. It is indicated that lowering the expression of LASS2 is likely to serve as an unprecedented approach for the treatment of ovarian cancer. 相似文献
996.
997.
Chunhui Sun Qiaoqiao Diao Jun Lu Zifeng Zhang Dongmei Wu Xingqi Wang Jun Xie Guihong Zheng Qun Shan Shaohua Fan Bin Hu Yuanlin Zheng 《Journal of cellular physiology》2019,234(5):5926-5939
Autophagy is a vital negative factor regulating cellular senescence. Purple sweet potato color (PSPC), one type of flavonoid, has been demonstrated to suppress endothelial senescence and restore endothelial function in diabetic mice by inhibiting the nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing protein 3 (NLRP3) inflammasome. However, the roles of autophagy in the inflammatory response during endothelial senescence are unknown. Here, we found that PSPC augmented autophagy to restrict high-glucose-induced premature endothelial senescence. In addition, PSPC administration impaired endothelium aging in diabetic mice by increasing autophagy. Inhibition of autophagy accelerated endothelial senescence, while enhancement of autophagy delayed senescence. Moreover, deactivation of the NLRP3 inflammasome triggered by PSPC was autophagy-dependent. Autophagy receptor microtubule-associated protein 1 light chain 3 and p62 interacted with the inflammasome component NLRP3, suggesting that autophagosomes target the NLRP3 inflammasome and deliver it to the lysosome for degradation. Altogether, PSPC amplified cellular autophagy, subsequently attenuated NLRP3 inflammasome activity and finally delayed endothelial senescence to ameliorate cardiovascular complication. These results suggest a potential therapeutic target in senescence-related cardiovascular diseases. 相似文献
998.
Fujin Shen Hongyun Zheng Limei Zhou Wei Li Juan Liu Xuexian Xu 《Journal of cellular physiology》2019,234(5):7004-7011
Cervical cancer (CC) is the most common malignant tumor with poor clinical outcome among women. Identification of novel biomarkers could be beneficial for the clinical diagnosis and treatment of CC. This study aimed to identify prognostic biomarkers for the prediction of prognostic status of CC patients, and explore the effect of the corresponding methylated genes in the occurrence and development of CC. The methylation microarray data of CC was extracted from The Cancer Genome Atlas (TCGA) dataset. The methylation genes associated with the prognostic status were identified based on the information of the relapse-free survival (RFS) of the CC patients. The prognostic gene pairs were further identified. Then, the prognostic signature was identified by the forward search algorithm based on the C-index method. The results were validated by independent dataset. Finally, the functional analysis was performed on the methylation genes. A total of 276 methylation genes and 2508 gene pairs associated with the prognostic status of the CC were identified. A signature composed of eight methylation gene pairs was obtained to predict the prognostic status of cervical patients. A series of genes that played an important role in the occurrence and development of CC were obtained by the functional enrichment analysis. To summary, a prognostic signature consisting of eight methylation gene pairs was obtained. Of note, the CD28 and PTEN gene pair were found to play important roles in the occurrence and development of CC. 相似文献
999.
1000.
Yu Wang Ye Liu Junwei Li Yi Yang Xiaomeng Ni Haijiao Cheng Teng Huang Yanmei Guo Hongwu Ma Ping Zheng Meng Wang Jibin Sun Yanhe Ma 《Biotechnology and bioengineering》2019,116(11):i-i
CRISPR/Cas9-guided cytidine deaminase enables C:G to T:A base editing in bacterial genome without introduction of lethal double-stranded DNA break, supplement of foreign DNA template, or dependence on inefficient homologous recombination. However, limited by genome-targeting scope, editing window, and base transition capability, the application of base editing in metabolic engineering has not been explored. Herein, four Cas9 variants accepting different protospacer adjacent motif (PAM) sequences were used to increase the genome-targeting scope of bacterial base editing. After a comprehensive evaluation, we demonstrated that PAM requirement of bacterial base editing can be relaxed from NGG to NG using the Cas9 variants, providing 3.9-fold more target loci for gene inactivation in Corynebacterium glutamicum. Truncated or extended guide RNAs were employed to expand the canonical 5-bp editing window to 7-bp. Bacterial adenine base editing was also achieved with Cas9 fused to adenosine deaminase. With these updates, base editing can serve as an enabling tool for fast metabolic engineering. To demonstrate its potential, base editing was used to deregulate feedback inhibition of aspartokinase via amino acid substitution for lysine overproduction. Finally, a user-friendly online tool named gBIG was provided for designing guide RNAs for base editing-mediated inactivation of given genes in any given sequenced genome ( www.ibiodesign.net/gBIG ). 相似文献