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https://www.readbyqxmd.com/read/29321472/desumoylase-senp6-maintains-osteochondroprogenitor-homeostasis-by-suppressing-the-p53-pathway
#1
Jianshuang Li, Di Lu, Hong Dou, Huadie Liu, Kevin Weaver, Wenjun Wang, Jiada Li, Edward T H Yeh, Bart O Williams, Tao Yang, Ling Zheng
The development, growth, and renewal of skeletal tissues rely on the function of osteochondroprogenitors (OCPs). Protein sumoylation/desumoylation has emerged as a pivotal mechanism for stem cell/progenitor homeostasis, and excessive sumoylation has been associated with cell senescence and tissue aging, but its role in regulating OCP function is unclear. Here we show that postnatal loss of the desumoylase SUMO1/sentrin-specific peptidase 6 (SENP6) causes premature aging. OCP-specific SENP6 knockout mice exhibit smaller skeletons, with elevated apoptosis and cell senescence in OCPs and chondrocytes...
January 10, 2018: Nature Communications
https://www.readbyqxmd.com/read/29311642/hsp90-inhibition-alters-the-chemotherapy-driven-rearrangement-of-the-oncogenic-secretome
#2
Simona di Martino, Carla Azzurra Amoreo, Barbara Nuvoli, Rossella Galati, Sabrina Strano, Francesco Facciolo, Gabriele Alessandrini, Harvey I Pass, Gennaro Ciliberto, Giovanni Blandino, Ruggero De Maria, Mario Cioce
Adaptive resistance to therapy is a hallmark of cancer progression. To date, it is not entirely clear how microenvironmental stimuli would mediate emergence of therapy-resistant cell subpopulations, although a rearrangement of the cancer cell secretome following therapy-induced stress can be pivotal for such a process. Here, by using the highly chemoresistant malignant pleural mesothelioma (MPM) as an experimental model, we unveiled a key contribution of the chaperone HSP90 at assisting a chemotherapy-instigated Senescence-Associated-Secretory-Phenotype (SASP)...
January 9, 2018: Oncogene
https://www.readbyqxmd.com/read/29258883/cartilage-regeneration-and-ageing-targeting-cellular-plasticity-in-osteoarthritis
#3
REVIEW
Marta Varela-Eirin, Jesus Loureiro, Eduardo Fonseca, Silvia Corrochano, Jose R Caeiro, Manuel Collado, Maria D Mayan
Ageing processes play a major contributing role for the development of Osteoarthritis (OA). This prototypic degenerative condition of ageing is the most common form of arthritis and is accompanied by a general decline, chronic pain and mobility deficits. The disease is primarily characterized by articular cartilage degradation, followed by subchondral bone thickening, osteophyte formation, synovial inflammation and joint degeneration. In the early stages, osteoarthritic chondrocytes undergo phenotypic changes that increase cell proliferation and cluster formation and enhance the production of matrix-remodelling enzymes...
December 16, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/29206223/a-model-of-the-onset-of-the-senescence-associated-secretory-phenotype-after-dna-damage-induced-senescence
#4
Patrick Meyer, Pallab Maity, Andre Burkovski, Julian Schwab, Christoph Müssel, Karmveer Singh, Filipa F Ferreira, Linda Krug, Harald J Maier, Meinhard Wlaschek, Thomas Wirth, Hans A Kestler, Karin Scharffetter-Kochanek
Cells and tissues are exposed to stress from numerous sources. Senescence is a protective mechanism that prevents malignant tissue changes and constitutes a fundamental mechanism of aging. It can be accompanied by a senescence associated secretory phenotype (SASP) that causes chronic inflammation. We present a Boolean network model-based gene regulatory network of the SASP, incorporating published gene interaction data. The simulation results describe current biological knowledge. The model predicts different in-silico knockouts that prevent key SASP-mediators, IL-6 and IL-8, from getting activated upon DNA damage...
December 4, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/29201428/effect-of-aging-on-the-female-reproductive-function
#5
REVIEW
Koumei Shirasuna, Hisataka Iwata
Aging is a complex biological process that involves the accrual of bodily changes over a long life span. In humans, advanced maternal age is associated with infertility and adverse pregnancy complications. Cellular and organic senescence is hypothesized to contribute to the age-related decline in reproductive function. Accumulating evidence suggests that immune cells play pivotal roles in physiological reproductive function and pregnancy. The concept of "inflammaging" has recently emerged- an age-dependent, low-grade, chronic, and systemic inflammatory state induced by the senescence-associated secretory phenotype (SASP), which is produced by the innate immune, parenchymal, and nonparenchymal cells within the organs...
2017: Contraception and Reproductive Medicine
https://www.readbyqxmd.com/read/29201175/anti-inflammatory-effects-of-fagopyrum-cymosum-administered-as-a-potential-drug-for-ulcerative-colitis
#6
Fei Ge, Shilin Zhu, Lina Liu, Jing Yan, Yu Ji, Zhiguang Sun
Fagopyrum cymosum (Trev.) Meisn (Fag), which belongs to the Polygonaceae family, has been widely used to treat inflammatory diseases. Previous studies have revealed that Fag components exhibit anti-inflammatory activities; however, their potential use in treating inflammatory bowel disease (IBD) has not been explored. In the present study, mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis were used as a model of IBD. Fag extract was orally administered for 3 days following the induction of colitis and the conventional drug, salicylazosulfapyridine (SASP), was used as a control...
November 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29197623/dual-effects-of-sulfasalazine-on-rat-sperm-characteristics-spermatogenesis-and-steroidogenesis-in-two-experimental-models
#7
Mohammad Mehdi Ommati, Reza Heidari, Akram Jamshidzadeh, Mohammad Javad Zamiri, Zilong Sun, Samira Sabouri, Jundong Wang, Fatemeh Ahmadi, Nafiseh Javanmard, Kazem Seifi, Saeed Mousapour, Babak Shirazi Yeganeh
There are reports of sulfasalazine (Salazosulfapyridine; SASP)-induced reproductive toxicity, but there it is not known whether the SASP molecule or its intestinal metabolites are responsible for this effect. Rats received SASP (150, 300, and 600mg/kg) for 60 consecutive days (in vivo). Additionally, epididymal sperm was isolated and incubated with SASP (10μM-1600μM) (in vitro). Markers of oxidative stress, mitochondrial function, and sperm functionality, along with testis histopathology as well as several steroidogenic genes and proteins, including steroidogenic acute regulatory (StAR) protein, cytochrome P450 side chain cleavage enzyme (P450scc; Cyp11a), 3β-hydroxysteroid dehydrogenase (3β-HSD), 17β-hydroxysteroid dehydrogenase (17β-HSD) were measured...
November 29, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29186801/epigenetic-basis-of-cellular-senescence-and-its-implications-in-aging
#8
REVIEW
(no author information available yet)
Cellular senescence is a tumor suppressive response that has become recognized as a major contributor of tissue aging. Senescent cells undergo a stable proliferative arrest that protects against neoplastic transformation, but acquire a secretory phenotype that has long-term deleterious effects. Studies are still unraveling the effector mechanisms that underlie these senescence responses with the goal to identify therapeutic interventions. Such effector mechanisms have been linked to the dramatic remodeling in the epigenetic and chromatin landscape that accompany cellular senescence...
November 24, 2017: Genes
https://www.readbyqxmd.com/read/29180744/stem-cell-senescence-drives-age-attenuated-induction-of-pituitary-tumours-in-mouse-models-of-paediatric-craniopharyngioma
#9
Jose Mario Gonzalez-Meljem, Scott Haston, Gabriela Carreno, John R Apps, Sara Pozzi, Christina Stache, Grace Kaushal, Alex Virasami, Leonidas Panousopoulos, Seyedeh Neda Mousavy-Gharavy, Ana Guerrero, Mamunur Rashid, Nital Jani, Colin R Goding, Thomas S Jacques, David J Adams, Jesus Gil, Cynthia L Andoniadou, Juan Pedro Martinez-Barbera
Senescent cells may promote tumour progression through the activation of a senescence-associated secretory phenotype (SASP), whether these cells are capable of initiating tumourigenesis in vivo is not known. Expression of oncogenic β-catenin in Sox2+ young adult pituitary stem cells leads to formation of clusters of stem cells and induction of tumours resembling human adamantinomatous craniopharyngioma (ACP), derived from Sox2- cells in a paracrine manner. Here, we uncover the mechanisms underlying this paracrine tumourigenesis...
November 28, 2017: Nature Communications
https://www.readbyqxmd.com/read/29174037/cellular-senescence-and-liver-disease-mechanisms-and-therapeutic-strategies
#10
REVIEW
Mei Guo
Cellular senescence is a fundamental cell fate caused by several cellular injuries which results in irreversible cell cycle arrest yet remaining metabolically active across all species. Cellular senescence not only can prevent tumor occurrence by inhibiting the proliferation of injured cells, but also can affect the surrounding cells through the senescence-associated secretory phenotype (SASP). Attractively, accumulating evidence shows that cellular senescence is closely related to various liver diseases. Therapeutic opportunities based on targeting senescent cells and the SASP are considered to be potential strategy for liver diseases...
November 22, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29146100/emerging-role-of-extracellular-vesicles-as-a-senescence-associated-secretory-phenotype-insights-into-the-pathophysiology-of-lung-diseases
#11
REVIEW
Tsukasa Kadota, Yu Fujita, Yusuke Yoshioka, Jun Araya, Kazuyoshi Kuwano, Takahiro Ochiya
Aging is a major risk factor for the development of chronic lung diseases such as chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and lung cancer. A main aspect of aging is the impaired function of maintaining homeostasis in the organs and body, which is associated with cellular senescence. Cellular senescence is recognized as the state of irreversible cell cycle arrest in response to a variety of cellular stresses. Senescent cells are not simply cell cycle-arrested cells; they also affect bystander cells through the secretion of bioactive molecules, termed the senescence-associated secretory phenotype (SASP)...
November 17, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/29143360/identification-of-a-pyridine-derivative-inducing-senescence-in-ovarian-cancer-cell-lines-via-p21-activation
#12
Dongsheng Shang, Yanfang Wu, Ya Ding, Ziwen Lu, Yanting Shen, Feifei Zhu, Hanqing Liu, Chunyin Zhu, Zhigang Tu
Cellular senescence is a state of irreversible cell growth arrest. Increasing evidence suggests that cellular senescence contribute to tumor suppression in vivo. However, only a few anti-cancer drugs have been discovered to induce cellular senescence. Searching for new compounds which can inhibit cancer cell growth by inducing senescence is becoming one of the most attractive research fields. To test the effects of candidate compounds on cancer cell growth, cell proliferation assays, senescence associated β-galactosidase (SA-β-gal) staining, and flow cytometry assay were performed...
November 16, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29138277/coupling-shrna-screens-with-single-cell-rna-seq-identifies-a-dual-role-for-mtor-in-reprogramming-induced-senescence
#13
Marieke Aarts, Athena Georgilis, Meryam Beniazza, Patrizia Beolchi, Ana Banito, Thomas Carroll, Marizela Kulisic, Daniel F Kaemena, Gopuraja Dharmalingam, Nadine Martin, Wolf Reik, Johannes Zuber, Keisuke Kaji, Tamir Chandra, Jesús Gil
Expression of the transcription factors OCT4, SOX2, KLF4, and cMYC (OSKM) reprograms somatic cells into induced pluripotent stem cells (iPSCs). Reprogramming is a slow and inefficient process, suggesting the presence of safeguarding mechanisms that counteract cell fate conversion. One such mechanism is senescence. To identify modulators of reprogramming-induced senescence, we performed a genome-wide shRNA screen in primary human fibroblasts expressing OSKM. In the screen, we identified novel mediators of OSKM-induced senescence and validated previously implicated genes such as CDKN1A We developed an innovative approach that integrates single-cell RNA sequencing (scRNA-seq) with the shRNA screen to investigate the mechanism of action of the identified candidates...
November 14, 2017: Genes & Development
https://www.readbyqxmd.com/read/29133134/sensing-the-breaks-cytosolic-chromatin-in-senescence-and-cancer
#14
Raffaella Di Micco
Cellular senescence constitutes a stable growth arrest characterized by DNA damage response (DDR) activation and by the senescence-associated secretory phenotype (SASP). SASP, through its paracrine effects, stimulates the immune system for senescence eradication. Similarly, chemotherapy-treated cancers activate an interferon-mediated response to induce anti-tumor immunity. Recent studies now uncover a new role for the innate DNA sensing pathway in the recognition of cytosolic chromatin in senescence and cancer...
November 10, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29089421/genetic-interrogation-of-replicative-senescence-uncovers-a-dual-role-for-usp28-in-coordinating-the-p53-and-gata4-branches-of-the-senescence-program
#15
Anna E Mazzucco, Agata Smogorzewska, Chanhee Kang, Ji Luo, Michael R Schlabach, Qikai Xu, Rupesh Patel, Stephen J Elledge
Senescence is a terminal differentiation program that halts the growth of damaged cells and must be circumvented for cancer to arise. Here we describe a panel of genetic screens to identify genes required for replicative senescence. We uncover a role in senescence for the potent tumor suppressor and ATM substrate USP28. USP28 controls activation of both the TP53 branch and the GATA4/NFkB branch that controls the senescence-associated secretory phenotype (SASP). These results suggest a role for ubiquitination in senescence and imply a common node downstream from ATM that links the TP53 and GATA4 branches of the senescence response...
October 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/29084133/modulation-of-the-senescence-associated-inflammatory-phenotype-in-human-fibroblasts-by-olive-phenols
#16
Beatrice Menicacci, Caterina Cipriani, Francesca Margheri, Alessandra Mocali, Lisa Giovannelli
Senescent cells display an increase in the secretion of growth factors, inflammatory cytokines and proteolytic enzymes, termed the "senescence-associated-secretory-phenotype" (SASP), playing a major role in many age-related diseases. The phenolic compounds present in extra-virgin olive oil are inhibitors of oxidative damage and have been reported to play a protective role in inflammation-related diseases. Particularly, hydroxytyrosol and oleuropein are the most abundant and more extensively studied. Pre-senescent human lung (MRC5) and neonatal human dermal (NHDF) fibroblasts were used as cellular model to evaluate the effect of chronic (4-6 weeks) treatment with 1 μM hydroxytyrosol (HT) or 10 μM oleuropein aglycone (OLE) on senescence/inflammation markers...
October 30, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29074538/tgf-%C3%AE-promotes-genomic-instability-after-loss-of-runx3
#17
Vaidehi Krishnan, Yu Lin Chong, Tuan Zea Tan, Madhura D Kulkarni, Muhammad Bakhait Bin Rahmat, Lavina Sierra Tay, Doorgesh S Jokhun, Amudha Ganesan, Linda Shyue Huey Chuang, Dominic Chih-Cheng Voon, Shivashankar Gv, Jean Paul Thiery, Yoshiaki Ito
Studies of genomic instability have historically focused on intrinsic mechanisms rather than extrinsic mechanisms based on the tumor microenvironment (TME). TGF-β is the most abundantly secreted cytokine in the TME where it imparts various aggressive characteristics including invasive migration, drug resistance and epithelial-to-mesenchymal transition (EMT). Here we show that TGF-β also promotes genomic instability in the form of DNA double strand breaks (DSB) in cancer cells which lack the tumor suppressor gene RUNX3...
October 26, 2017: Cancer Research
https://www.readbyqxmd.com/read/29052866/runx-mediated-growth-arrest-and-senescence-are-attenuated-by-diverse-mechanisms-in-cells-expressing-runx1-fusion-oncoproteins
#18
Gail Anderson, Nancy Mackay, Kathryn Gilroy, Jodie Hay, Gillian Borland, Alma McDonald, Margaret Bell, Siti Ayuni Hassanudin, Ewan Cameron, James C Neil, Anna Kilbey
RUNX gene over-expression inhibits growth of primary cells but transforms cells with tumor suppressor defects, consistent with reported associations with tumor progression. In contrast, chromosomal translocations involving RUNX1 are detectable in utero, suggesting an initiating role in leukemias. How do cells expressing RUNX1 fusion oncoproteins evade RUNX-mediated growth suppression? Previous studies showed that the TEL-RUNX1 fusion from t(12;21) B-ALLs is unable to induce senescence-like growth arrest (SLGA) in primary fibroblasts while potent activity is displayed by the RUNX1-ETO fusion found in t(8;21) AMLs...
October 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29044508/differentially-regulated-gene-expression-in-quiescence-vs-senescence-and-identification-of-arid5a-as-a-quiescence-associated-marker
#19
Tarique Anwar, Bijoya Sen, Savera Aggarwal, Rhisita Nath, Ajay Katoch, Mohamed Aiyaz, Nirupma Trehanpati, Sanjeev Khosla, Gayatri Ramakrishna
In multicellular organisms majority of the cells remain in a non-dividing states of either fully differentiated or quiescence (reversible) or senescence (irreversible) conditions. In the present study, gene expression signatures unique to quiescence and senescence were identified using microarray in osteosarcoma cell line, U2OS. Besides, it was also noted that certain genes and pathways like NOD pathway was shared by both the growth arrest conditions. A major highlight of the present study was increased expression of number of chemokines and cytokines in both quiescence and senescence...
October 17, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29041897/small-molecule-modulation-of-splicing-factor-expression-is-associated-with-rescue-from-cellular-senescence
#20
Eva Latorre, Vishal C Birar, Angela N Sheerin, J Charles C Jeynes, Amy Hooper, Helen R Dawe, David Melzer, Lynne S Cox, Richard G A Faragher, Elizabeth L Ostler, Lorna W Harries
BACKGROUND: Altered expression of mRNA splicing factors occurs with ageing in vivo and is thought to be an ageing mechanism. The accumulation of senescent cells also occurs in vivo with advancing age and causes much degenerative age-related pathology. However, the relationship between these two processes is opaque. Accordingly we developed a novel panel of small molecules based on resveratrol, previously suggested to alter mRNA splicing, to determine whether altered splicing factor expression had potential to influence features of replicative senescence...
October 17, 2017: BMC Cell Biology
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