• Title/Summary/Keyword: cellular signaling pathway

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Stem-leaf saponins from Panax notoginseng counteract aberrant autophagy and apoptosis in hippocampal neurons of mice with cognitive impairment induced by sleep deprivation

  • Cao, Yin;Yang, Yingbo;Wu, Hui;Lu, Yi;Wu, Shuang;Liu, Lulu;Wang, Changhong;Huang, Fei;Shi, Hailian;Zhang, Beibei;Wu, Xiaojun;Wang, Zhengtao
    • Journal of Ginseng Research
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    • v.44 no.3
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    • pp.442-452
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    • 2020
  • Backgroud: Sleep deprivation (SD) impairs learning and memory by inhibiting hippocampal functioning at molecular and cellular levels. Abnormal autophagy and apoptosis are closely associated with neurodegeneration in the central nervous system. This study is aimed to explore the alleviative effect and the underlying molecular mechanism of stem-leaf saponins of Panax notoginseng (SLSP) on the abnormal neuronal autophagy and apoptosis in hippocampus of mice with impaired learning and memory induced by SD. Methods: Mouse spatial learning and memory were assessed by Morris water maze test. Neuronal morphological changes were observed by Nissl staining. Autophagosome formation was examined by transmission electron microscopy, immunofluorescent staining, acridine orange staining, and transient transfection of the tf-LC3 plasmid. Apoptotic event was analyzed by flow cytometry after PI/annexin V staining. The expression or activation of autophagy and apoptosis-related proteins were detected by Western blotting assay. Results: SLSP was shown to improve the spatial learning and memory of mice after SD for 48 h, accomanied with restrained excessive autophage and apoptosis, whereas enhanced activation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway in hippocampal neurons. Meanwhile, it improved the aberrant autophagy and apoptosis induced by rapamycin and re-activated phosphoinositide 3-kinase/Akt/mammalian target of rapamycin signaling transduction in HT-22 cells, a hippocampal neuronal cell line. Conclusion: SLSP could alleviate cognitive impairment induced by SD, which was achieved probably through suppressing the abnormal autophagy and apoptosis of hippocampal neurons. The findings may contribute to the clinical application of SLSP in the prevention or therapy of neurological disorders associated with SD.

Beneficial Effects of Acanthopanax senticosus Extract in Type II Diabetes Animal Model via Down-Regulation of Advanced Glycated Hemoglobin and Glycosylation End Products (제2형 당뇨 동물모델에서 가시오가피 추출물의 당화혈색소 및 최종당화산물 억제를 통한 혈당조절 효과)

  • Kwon, Han Ol;Lee, Minhee;Kim, Yong Jae;Kim, Eun;Kim, Ok-Kyung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.7
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    • pp.929-937
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    • 2016
  • The purpose of this study was to investigate the effect of Acanthopanax senticosus extract (ASE) (ethanol : DW=1:1, v/v) on inhibition of type 2 diabetes using an OLETF rat model via regulation of HbA1c and AGEs levels. Supplementation with ASE 0.1% and 0.5% effectively lowered levels of glucose, insulin, oral glucose tolerance test, and Homa-insulin resistance, suggesting reduced insulin resistance. Blood levels of HbA1c and AGEs were significantly reduced in a dose-dependent manner. As oxidative stress plays a key role in accelerating production of HbA1c and AGEs, which worsen symptoms of type 2 diabetes, levels of malonaldehyde and pro-inflammatory cytokines were measured. Lipid peroxidation in both blood and liver tissues was significantly reduced, and induction of pro-inflammatory cytokines interleukin-${\beta}$ and tumor necrosis factor-${\alpha}$, which elevate production of HbA1c and AGEs, was inhibited (P<0.05). To evaluate the possible cellular events after AGEs receptor activation, genetic expression of protein kinase C (PKC)-${\delta}$ and transforming growth factor (TGF)-${\beta}$ was measured by real-time polymerase chain reaction. Supplementation with both ASE 0.1% and 0.5% significantly inhibited mRNA expression of PKC-${\delta}$ and TGF-${\beta}$, indicating that ASE may have beneficial effects on preventing insulin-resistant cells or tissues from progressing to diabetic complications. Taken together, ASE has potential to improve type 2 diabetes by inhibiting insulin resistance and protein glycosylation, including production of HbA1c and AGEs. Anti-oxidative activities of ASE are a main requisite for reducing production of HbA1c and AGEs and are also related to regulation of the PKC signaling pathway, resulting in suppression of TGF-${\beta}$, which increases synthesis of collagen, prostaglandin, and disease-related proteins.

Antioxidant and Cytoprotective Effects of Socheongja and Socheong 2, Korean Black Seed Coat Soybean Varieties, against Hydrogen Peroxide-induced Oxidative Damage in HaCaT Human Skin Keratinocytes (HaCaT 인간 피부 각질세포에서 과산화수소 유도 산화 손상에 대한 소청자 및 소총2호의 항산화 및 세포보호 효능)

  • Choi, Eun Ok;Kwon, Da Hye;Hwang, Hye-Jin;Kim, Kook Jin;Lee, Dong Hee;Choi, Yung Hyun
    • Journal of Life Science
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    • v.28 no.4
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    • pp.454-464
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    • 2018
  • Black soybeans are used as food sources as well as for traditional medicines because they contain an abundance of natural phenolic compounds. In this study, total phenolic contents (TPCs) of Korean black seed coat soybean varieties Socheongja (SCJ), Socheong 2 (SC2) and Cheongja 2 (CJ2) as well as their antioxidant capacities were investigated. Among them, TPCs were abundantly present in the order of CJ2$H_2O_2$-stimulated HaCaT human keratinocytes. Our results revealed that treatment with SCJ and SC2 prior to $H_2O_2$ exposure significantly increases the viability of HaCaT cells, indicating that the exposure of HaCaT cells to SCJ and SC2 conferred a protective effect against oxidative stress. SCJ and SC2 also effectively inhibited $H_2O_2$-induced apoptotic cell death through the blocking of mitochondrial dysfunction. SCJ and SC2 also attenuated the phosphorylation of Histone H2AX. Furthermore, they effectively induced the levels of thioredoxin reductase (TrxR) 1, a potent antioxidant enzyme, which is associated with the induction of nuclear transcription factor erythroid-2-like factor 2 (Nrf2); however, the protective effects of SCJ and SC2 were significantly reversed by Auranofin, a TrxR inhibitor. These results indicate that they have protective activity through the blocking of cellular damage related to oxidative stress via the Nrf2 signaling pathway. In conclusion, our study indicated that SCJ and SC2 might potentially serve as novel agents for the treatment and prevention of skin disorders caused by oxidative stress.

Genome-Wide Analysis of DNA Methylation before- and after Exercise in the Thoroughbred Horse with MeDIP-Seq

  • Gim, Jeong-An;Hong, Chang Pyo;Kim, Dae-Soo;Moon, Jae-Woo;Choi, Yuri;Eo, Jungwoo;Kwon, Yun-Jeong;Lee, Ja-Rang;Jung, Yi-Deun;Bae, Jin-Han;Choi, Bong-Hwan;Ko, Junsu;Song, Sanghoon;Ahn, Kung;Ha, Hong-Seok;Yang, Young Mok;Lee, Hak-Kyo;Park, Kyung-Do;Do, Kyoung-Tag;Han, Kyudong;Yi, Joo Mi;Cha, Hee-Jae;Ayarpadikannan, Selvam;Cho, Byung-Wook;Bhak, Jong;Kim, Heui-Soo
    • Molecules and Cells
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    • v.38 no.3
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    • pp.210-220
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    • 2015
  • Athletic performance is an important criteria used for the selection of superior horses. However, little is known about exercise-related epigenetic processes in the horse. DNA methylation is a key mechanism for regulating gene expression in response to environmental changes. We carried out comparative genomic analysis of genome-wide DNA methylation profiles in the blood samples of two different thoroughbred horses before and after exercise by methylated-DNA immunoprecipitation sequencing (MeDIP-Seq). Differentially methylated regions (DMRs) in the pre-and post-exercise blood samples of superior and inferior horses were identified. Exercise altered the methylation patterns. After 30 min of exercise, 596 genes were hypomethy-lated and 715 genes were hypermethylated in the superior horse, whereas in the inferior horse, 868 genes were hypomethylated and 794 genes were hypermethylated. These genes were analyzed based on gene ontology (GO) annotations and the exercise-related pathway patterns in the two horses were compared. After exercise, gene regions related to cell division and adhesion were hypermethylated in the superior horse, whereas regions related to cell signaling and transport were hypermethylated in the inferior horse. Analysis of the distribution of methylated CpG islands confirmed the hypomethylation in the gene-body methylation regions after exercise. The methylation patterns of transposable elements also changed after exercise. Long interspersed nuclear elements (LINEs) showed abundance of DMRs. Collectively, our results serve as a basis to study exercise-based reprogramming of epigenetic traits.