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31.
32.
Short‐term calorie restriction ameliorates genomewide,age‐related alterations in DNA methylation
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Chul Hong Kim Eun Kyeong Lee Yeon Ja Choi Hye Jin An Hyeong Oh Jeong Daeui Park Byoung Chul Kim Byung Pal Yu Jong Bhak Hae Yung Chung 《Aging cell》2016,15(6):1074-1081
DNA methylation plays major roles in many biological processes, including aging, carcinogenesis, and development. Analyses of DNA methylation using next‐generation sequencing offer a new way to profile and compare methylomes across the genome in the context of aging. We explored genomewide DNA methylation and the effects of short‐term calorie restriction (CR) on the methylome of aged rat kidney. Whole‐genome methylation of kidney in young (6 months old), old (25 months old), and OCR (old with 4‐week, short‐term CR) rats was analyzed by methylated DNA immunoprecipitation and next‐generation sequencing (MeDIP‐Seq). CpG islands and repetitive regions were hypomethylated, but 5′‐UTR, exon, and 3′‐UTR hypermethylated in old and OCR rats. The methylation in the promoter and intron regions was decreased in old rats, but increased in OCR rats. Pathway enrichment analysis showed that the hypermethylated promoters in old rats were associated with degenerative phenotypes such as cancer and diabetes. The hypomethylated promoters in old rats related significantly to the chemokine signaling pathway. However, the pathways significantly enriched in old rats were not observed from the differentially methylated promoters in OCR rats. Thus, these findings suggest that short‐term CR could partially ameliorate age‐related methylation changes in promoters in old rats. From the epigenomic data, we propose that the hypermethylation found in the promoter regions of disease‐related genes during aging may indicate increases in susceptibility to age‐related diseases. Therefore, the CR‐induced epigenetic changes that ameliorate age‐dependent aberrant methylation may be important to CR's health‐ and life‐prolonging effects. 相似文献
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Yen‐Yu Lu Yao‐Chang Chen Yu‐Hsun Kao Yung‐Kuo Lin Yung‐Hsin Yeh Shih‐Ann Chen Yi‐Jen Chen 《Journal of cellular and molecular medicine》2016,20(6):1182-1190
Colchicine is a microtubule disruptor that reduces the occurrence of atrial fibrillation (AF) after an operation or ablation. However, knowledge of the effects of colchicine on atrial myocytes is limited. The aim of this study was to determine if colchicine can regulate calcium (Ca2+) homeostasis and attenuate the electrical effects of the extracellular matrix on atrial myocytes. Whole‐cell clamp, confocal microscopy with fluorescence, and western blotting were used to evaluate the action potential and ionic currents of HL‐1 cells treated with and without (control) colchicine (3 nM) for 24 hrs. Compared with control cells, colchicine‐treated HL‐1 cells had a longer action potential duration with smaller intracellular Ca2+ transients and sarcoplasmic reticulum (SR) Ca2+ content by 10% and 47%, respectively. Colchicine‐treated HL‐1 cells showed a smaller L‐type Ca2+ current, reverse mode sodium–calcium exchanger (NCX) current and transient outward potassium current than control cells, but had a similar ultra‐rapid activating outward potassium current and apamin‐sensitive small‐conductance Ca2+‐activated potassium current compared with control cells. Colchicine‐treated HL‐1 cells expressed less SERCA2a, total, Thr17‐phosphorylated phospholamban, Cav1.2, CaMKII, NCX, Kv1.4 and Kv1.5, but they expressed similar levels of the ryanodine receptor, Ser16‐phosphorylated phospholamban and Kv4.2. Colchicine attenuated the shortening of the collagen‐induced action potential duration in HL‐1 cells. These findings suggest that colchicine modulates the atrial electrical activity and Ca2+ regulation and attenuates the electrical effects of collagen, which may contribute to its anti‐AF activity. 相似文献
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Suresh Anand Sadananthan Mya Thway Tint Navin Michael Izzuddin M. Aris See Ling Loy Kuan Jin Lee Lynette Pei‐Chi Shek Fabian Kok Peng Yap Kok Hian Tan Keith M. Godfrey Melvin Khee‐Shing Leow Yung Seng Lee Michael S. Kramer Peter D. Gluckman Yap Seng Chong Neerja Karnani Christiani Jeyakumar Henry Marielle Valerie Fortier S. Sendhil Velan 《Obesity (Silver Spring, Md.)》2019,27(3):470-478
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Cell adhesion to a scaffold is a prerequisite for tissue engineering. Many studies have been focused on enhancing cell adhesion to synthetic materials that are used for scaffold fabrication. Previously, we showed that immobilization of biotin molecules to chondrocyte surfaces enhanced cell adhesion to avidin-coated biodegradable polymers such as poly-L-lactic acid, poly-D,L-lactic acid and polycaprolactone. However, the endocytosis of cell membrane biotin molecules decreases binding strength between biotinylated-chondrocytes (B-chondrocytes) and avidin-coated substrata, and therefore decreases cell spreading and discourages long-term chondrocytes culture. In this study, we proposed two strategies to solve the shortcoming of the avidin-biotin binding system. First, the avidin-biotin binding system is combined with the intrinsic integrin-dependent adhesion systems in order to enhance long-term cell culture. Second, the incubation temperature is lowered in order to slow down the endocytosis process. We found that the avidin-biotin binding system in combination with FN-integrin binding system enhanced cell adhesion, cell spreading and cell growth. Decrease of cell culture temperature to 4 degrees C enhanced the adhesion of B-chondrocytes to the avidin-coated surfaces, but decreased cell viability and proliferation, compared to culture temperature of 37 degrees C. Whether there is an optimal seeding temperature between 4 and 37 degrees C for both adhesion and proliferation of B-chondrocytes needs further investigation. Our results indicated that modulation of the adhesion conditions could further enhance the efficacy of the avidin-biotin binding system in mediating cell adhesion, and subsequent tissue culture. 相似文献
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Lian Liu Kwang Seok Ahn Muthu K Shanmugam Hong Wang Hongyuan Shen Frank Arfuso Arunachalam Chinnathambi Sulaiman Ali Alharbi Yung Chang Gautam Sethi Feng Ru Tang 《Journal of cellular biochemistry》2019,120(3):4504-4513
Oleuropein is one of the most abundant phenolic compounds found in olives. Epidemiological studies have indicated that an increasing intake of olive oil can significantly reduce the risk of breast cancer. However, the potential effect(s) of oleuropein on estrogen receptor (ER)-negative breast cancer is not fully understood. This study aims to understand the anticancer effects and underlying mechanism(s) of oleuropein on ER-negative breast cancer cells in vitro. The effect of oleuropein on the viability of breast cancer cell lines was examined by mitochondrial dye-uptake assay, apoptosis by flow cytometric analysis, nuclear factor-κB (NF-κB) activation by DNA binding/reporter assays and protein expression by Western blot analysis. In the present report, thiazolyl blue tetrazolium bromide assay results indicated that oleuropein inhibited the viability of breast cancer cells, and its effects were more pronounced on MDA-MB-231 as compared with MCF-7 cells. It was further found that oleuropein increased the level of reactive oxygen species and also significantly inhibited cellular migration and invasion. In addition, the activation of NF-κB was abrogated as demonstrated by Western blot analysis, NF-κB-DNA binding, and luciferase assays. Overall, the data indicates that oleuropein can induce substantial apoptosis via modulating NF-κB activation cascade in breast cancer cells. 相似文献
39.
Hepatitis delta virus (HDV) encodes two isoforms of delta antigens (HDAgs). The small form of HDAg is required for HDV RNA replication, while the large form of HDAg inhibits the viral replication and is required for virion assembly. In this study, we found that the expression of B23, a nucleolar phosphoprotein involved in disparate functions including nuclear transport, cellular proliferation, and ribosome biogenesis, is up-regulated by these two HDAgs. Using in vivo and in vitro experimental approaches, we have demonstrated that both isoforms of HDAg can interact with B23 and their interaction domains were identified as the NH(2)-terminal fragment of each molecule encompassing the nuclear localization signal but not the coiled-coil region of HDAg. Sucrose gradient centrifugation analysis indicated that the majority of small HDAg, but a lesser amount of the large HDAg, co-sedimented with B23 and nucleolin in the large nuclear complex. Transient transfection experiments also indicated that introducing exogenous full-length B23, but not a mutated B23 defective in HDAg binding, enhanced HDV RNA replication. All together, our results reveal that HDAg has two distinct effects on nucleolar B23, up-regulation of its gene expression and the complex formation, which in turn regulates HDV RNA replication. Therefore, this work demonstrates the important role of nucleolar protein in regulating the HDV RNA replication through the complex formation with the key positive regulator being small HDAg. 相似文献
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