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P65 And Senescence

Lei Zhang, Jing Zhao, Aditi Gurkar, Laura J Niedernhofer, Paul D Robbins
Nuclear factor κB (NF-κB) is a family of transcription factors important for regulating innate and adaptive immunity, cellular proliferation, apoptosis and senescence. The NF-κB family is comprised of five subunits, RelA/p65, RelB, C-Rel, p50 (p105/NF-κB1), and p52 (p100/NF-κB2). NF-κB activity goes up with age in multiple tissues. The two subunits RelA/p65 and p50 have been implicated in senescence and aging with genetic deletion of p65 and p50 reducing or increasing senescence respectively. Pharmacologic inhibition of NF-κB also extends health span and reduces senescence in mouse models of accelerated aging...
2019: Methods in Molecular Biology
Zhi-Zhun Mo, Zhi-Xiu Lin, Zi-Ren Su, Lin Zheng, Hui-Lin Li, Jian-Hui Xie, Yan-Fang Xian, Tie-Gang Yi, Shui-Qing Huang, Jian-Ping Chen
Angelica sinensis (AS, Danggui in Chinese) is an important herbal component of various traditional formulae for the management of asthenia and its tonic effects. Although AS has been shown to ameliorate cognitive damage and nerve toxicity in D-galactose (D-gal)-elicited senescent mice brain, its effects on liver and kidney injury have not yet been explored. In this work, mice were subjected to hypodermic injection with D-gal (200 mg/kg) and orally gavaged with AS (20, 40, or 80 mg/kg) once a day for 8 successive weeks...
September 2018: Journal of Medicinal Food
Wei Xu, Yue Li, Wei-Wei Yuan, Yuan Yin, Wei-Wei Song, Yu Wang, Qi-Qing Huang, Wei-Hong Zhao, Jian-Qing Wu
BACKGROUND/AIMS: Cellular senescence acts as a barrier against tumorigenesis. The CD40L transgene, expressed in some tumor cells, not only becomes visible to antigen-presenting cells but also actively catalyzes its own termination. Here, we evaluated the effect of a membrane-bound mutant form of human CD40L (CD40L-M) on senescence and the senescence-associated secretory phenotype (SASP) in non-small cell lung cancer (NSCLC). METHODS: CD40 expression levels in the NSCLC cell lines A549/TR, A549/DDP and H460 were examined by flow cytometry...
2018: Cellular Physiology and Biochemistry
Hui Li, Yi-Feng Luo, Yong-Sheng Wang, Qing Yang, Yong-Long Xiao, Hou-Rong Cai, Can-Mao Xie
Pseudomonas aeruginosa (PA) is one of the most prevalent pathogens that cause nosocomial infection in critical patients. However, the mechanisms underlying macrophage growth status and functional changes during PA infection are yet unknown. In the present study, NADPH oxidase, gp91phox (NOX2) mediated macrophage to senescence in a PAO1 colony-dependent manner. gp91phox might regulate the senescence process through mutual interaction with the NF- κ B pathway. During infection, the overexpression or downregulation of gp91phox in macrophage could affect the nuclear activity of NF- κ B p65, while the downregulation of NF- κ B p65 led to a suppressed expression of gp91phox ...
2018: Oxidative Medicine and Cellular Longevity
Shan Liu, Zhaodi Zheng, Shuhua Ji, Tingting Liu, Yanhan Hou, Shasha Li, Guorong Li
Senescent cells display a senescence-associated secretory phenotype (SASP), which contributes to aging. Resveratrol, an activator of SIRT1, has anti-aging, anti-inflammatory, anti-oxidant, anti-free radical and other pharmacological effects. The genus of the annual fish Nothobranchius has become an emerging animal model for studying aging. However, the underlying mechanism for resveratrol to delay aging by SASP regulation has not been elucidated in vertebrates. In this study, the annual fish N. guentheri were fed with resveratrol for long-term treatment...
September 2018: Fish & Shellfish Immunology
Hiroyuki Moriyama, Mariko Moriyama, Toshiyuki Ozawa, Daisuke Tsuruta, Taro Iguchi, Satoshi Tamada, Tatsuya Nakatani, Koichi Nakagawa, Takao Hayakawa
Human adipose-derived mesenchymal stromal cells (hASCs) are attractive for regenerative medicine, but their limited in vitro life span limits their therapeutic applicability. Recent data demonstrate that hypoxia may benefit the ex vivo culture of stem cells. Such cells exhibit a high level of glycolytic metabolism under hypoxic conditions. However, the physiological role of glycolytic activation and its underlying regulatory mechanism are incompletely understood. We have shown that when activated under conditions of 5% O2 , Notch signaling dramatically increases the rate of glycolysis, improves proliferation efficiency, prevents senescence, and maintains the multipotency of hASCs...
July 1, 2018: Stem Cells and Development
Xian Cheng, Xin Yao, Shichen Xu, Jie Pan, Huixin Yu, Jiandong Bao, Haixia Guan, Rongrong Lu, Li Zhang
Papillary thyroid carcinoma (PTC) is the most common endocrine carcinoma. Our previous study revealed that punicalagin (PUN), an active component from pomegranate, triggered autophagic cell death and DNA damage response (DDR) in papillary thyroid carcinoma BCPAP cells. But the detailed anti-cancer mechanisms of punicalagin against PTC still remained to be further explored. DDR activation is a proven cause of cellular senescence, which mediates anti-tumor processes under certain circumstances. In this study, we reported that punicalagin treatment generated a senescent phenotype of BCPAP cells characterized as altered morphology, increased cell granularity and senescence-associated β-galactosidase (SA-β-Gal) staining...
July 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Roshni V Khatiwala, Shuning Zhang, Xiuchun Li, Neil Devejian, Edward Bennett, Chuanxi Cai
Autologous human cardiac stem/progenitor cell (hCPC) therapy is a promising treatment that has come into use in recent years for patients with cardiomyopathy. Though innovative in theory, a major hindrance to the practical application of this treatment is that the hCPCs of elderly patients, who are most susceptible to myocardial disease, are senescent and prone to cell death. Rejuvenating hCPCs from elderly patients may help overcome this obstacle, and can be accomplished by reversing entry into the cellular stage of senescence...
August 2018: Stem Cell Reviews
Guijuan Feng, Ke Zheng, Tong Cao, Jinlong Zhang, Min Lian, Dan Huang, Changbo Wei, Zhifeng Gu, Xingmei Feng
Dental pulp stem cells (DPSCs), one type of mesenchymal stem cells, are considered to be a type of tool cells for regenerative medicine and tissue engineering. Our previous studies found that the stimulation with lipopolysaccharide (LPS) might introduce senescence of DPSCs, and this senescence would have a positive correlation with the concentration of LPS. The β-galactosidase (SA-β-gal) staining was used to evaluate the senescence of DPSCs and immunofluorescence to show the morphology of DPSCs. Our findings suggested that the activity of SA-β-gal has increased after repeated stimulation with LPS and the morphology of DPSCs has changed with the stimulation with LPS...
June 2018: Cytotechnology
Hui Ling Ren, Chao Nan Lv, Ying Xing, Yuan Geng, Feng Zhang, Wei Bu, Ming Wei Wang
BACKGROUND We observed the effects of nuclear factor E2-related factor 2 (Nrf2) downregulation via intrahippocampal injection of a lentiviral vector on cognition in senescence-accelerated mouse prone 8 (SAMP8) to investigate the role of the (Nrf2)/antioxidant response element (ARE) pathway in age-related changes. MATERIAL AND METHODS Control lentivirus and Nrf2-shRNA-lentivirus were separately injected into the hippocampus of 4-month-old SAMR1 and SAMP8 mice and then successfully downregulated Nrf2 expression in this brain region...
February 23, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Anna Strzeszewska, Olga Alster, Grażyna Mosieniak, Agata Ciolko, Ewa Sikora
Senescence of cancer cells is an important outcome of treatment of many cancer types. Cell senescence is a permanent cell cycle arrest induced by stress conditions, including DNA damage. DNA damage activates DNA damage response (DDR), which involves members of the phosphatidylinositol 3-kinase-related kinase (PIKK) superfamily: protein kinases ATM, ATR, and DNA-PKcs. The so-far collected data indicate that ATM, with its downstream targets CHK2, p53, and p21, is the key protein involved in DDR-dependent senescence...
January 19, 2018: Cell Death & Disease
Haibin Wang, Guoxing Xu, Zhengjie Huang, Weizheng Li, Huali Cai, Yunda Zhang, Disheng Xiong, Gang Liu, Shengjie Wang, Zengfu Xue, Qi Luo
NLRP6, a member of the Nod-like receptor family, protects against chemically induced intestinal injury and colitis-associated colon cancer. However, the cellular mechanisms involved in this NLRP6-mediated protection remain unclear. Here, we show that NLRP6 was down-regulated in approximately 75% of primary gastric cancer cases and exhibited significant associations with advanced clinical-stage lymph node metastasis and poor overall survival. Functional studies established that ectopic overexpression or down-regulation of NLRP6 inhibited cancer cell proliferation by inducing cell cycle arrest at the G1 phase via P21 and Cyclin D1 both in vitro and in vivo ...
December 19, 2017: Oncotarget
Min Wang, Yanming Chen, Zhaojun Xiong, Shujie Yu, Bin Zhou, Yesheng Ling, Zhenda Zheng, Guangyao Shi, Yongxiang Wu, Xiaoxian Qian
Free fatty acids (FFAs) increase in visceral fat and are inferred to be one of the underlying inducers of adipose tissue inflammation. In our previous study, it was demonstrated that ginsenoside Rb1 stimulates endothelial nitric oxide synthase (eNOS) and Sirtuin 1 to protect against endothelial cell senescence. In the present study, 3T3‑L1 adipocytes were exposed to 0.5 mM FFAs with or without Rb1 (10‑40 µM). Monocyte chemotactic protein‑1 (MCP‑1) and interleukin‑6 (IL‑6) secretion was measured using ELISA...
December 2017: Molecular Medicine Reports
Chutikorn Nopparat, Puritat Sinjanakhom, Piyarat Govitrapong
Autophagy, a degradation mechanism that plays a major role in maintaining cellular homeostasis and diminishes in aging, is considered an aging characteristic. Melatonin is an important hormone that plays a wide range of physiological functions, including the anti-aging effect, potentially via the regulation of the Sirtuin1 (SIRT1) pathway. The deacetylation ability of SIRT1 is important for controlling the function of several transcription factors, including nuclear factor kappa B (NF-ĸB). Apart from inflammation, NF-ĸB can regulate autophagy by inhibiting Beclin1, an initiator of autophagy...
August 2017: Journal of Pineal Research
Chan Hum Park, Sung Ho Shin, Eun Kyeong Lee, Dae Hyun Kim, Min-Jo Kim, Seong-Soo Roh, Takako Yokozawa, Hae Young Chung
The present study was conducted to examine whether magnesium lithospermate B (MLB) extracted from Salviae miltiorrhizae radix was renoprotective in pathways related to age-related oxidative stress in aged rats. Magnesium lithospermate B was orally administered at a dose of 2- or 8-mg/kg body weight for 16 consecutive days, and the effects were compared with those of vehicle in old and young rats. Magnesium lithospermate B administration to old rats ameliorated renal oxidative stress through reduction of reactive oxygen species...
May 2017: Phytotherapy Research: PTR
Xiao-Zhi Bai, Ting He, Jian-Xin Gao, Yang Liu, Jia-Qi Liu, Shi-Chao Han, Yan Li, Ji-Hong Shi, Jun-Tao Han, Ke Tao, Song-Tao Xie, Hong-Tao Wang, Da-Hai Hu
Acute kidney injury (AKI) is a common complication after severe burns. Melatonin has been reported to protect against multiple organ injuries by increasing the expression of SIRT1, a silent information regulator that regulates stress responses, inflammation, cellular senescence and apoptosis. This study aimed to investigate the protective effects of melatonin on renal tissues of burned rats and the role of SIRT1 involving the effects. Rat severely burned model was established, with or without the administration of melatonin and SIRT1 inhibitor...
September 7, 2016: Scientific Reports
Murray Korc
Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer in which NF-κB pathways promote biological aggressiveness. In this issue of the JCI, Lesina et al. investigated the role of RelA, the p65 partner of p50 that together form the most common NF-κB complex, in the early stages of pancreatic malignant transformation and in established PDAC. By deleting Rela in the context of an oncogenic Kras-driven autochthonous model of PDAC, the authors demonstrated that RelA is a mediator of oncogene-induced senescence (OIS) and the senescence-associated secretory phenotype (SASP) that attenuates acinar-to-ductal metaplasia, pancreatic intraepithelial neoplasia (PanIN) formation, and PanIN progression to PDAC...
August 1, 2016: Journal of Clinical Investigation
Taewon Jin, Min Jeong Kim, Won Il Heo, Kui Young Park, Sun Young Choi, Mi-Kyung Lee, Seung-Phil Hong, Seong-Jin Kim, Myung Im, Nam Ju Moon, Seong Jun Seo
Stress-induced premature senescence or aging causes dysfunction in the human somatic system. Adiponectin (Acrp30) plays a role in functional recovery, especially with adenosine 3',5'-monophosphate (AMP)-activated protein kinase (AMPK) and silent mating type information regulation 2 homolog 1 (SIRT1). Acrp30 stimulation reduced the premature senescence positive ratio induced by hydrogen peroxide (H2O2) and restituted human β-defensin 2 (hBD-2) levels in senescent keratinocytes. Acrp30 recovered AMPK activity in senescent keratinocytes and increased SIRT1 deacetylation activity...
September 2, 2016: Biochemical and Biophysical Research Communications
Vengadeshprabhu Karuppagounder, Vijayasree V Giridharan, Somasundaram Arumugam, Remya Sreedhar, Suresh S Palaniyandi, Prasanna Krishnamurthy, Joao Quevedo, Kenichi Watanabe, Tetsuya Konishi, Rajarajan A Thandavarayan
The aim of this study was to investigate the role of macrophage polarization in aging heart. Macrophage differentiation is pathogenically linked to many inflammatory and immune disorders. It is often preceded by myocardial inflammation, which is characterized by increased cardiac damage and pro-inflammatory cytokine levels. Therefore, we investigated the hypothesis that senescence accelerated-prone (SAMP8) mice cardiac tissue would develop macrophage polarization compared with senescence-resistant control (SAMR1) mice...
2016: PloS One
Mariusz L Hartman, Beata Talar, Malgorzata Sztiller-Sikorska, Dariusz Nejc, Malgorzata Czyz
The activity of the M isoform of microphthalmia-associated transcription factor (MITF-M) has been attributed to regulation of differentiation, proliferation, survival and senescence of melanoma cells. MITF expression was shown to be antagonized by the activation of transcription factor NF-κB. Parthenolide, an inhibitor of NF-κB, has not been yet reported to affect MITF-M expression. Our results obtained in patient-derived melanoma cell populations indicate that parthenolide efficiently decreases the MITF-M level...
February 23, 2016: Oncotarget
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