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Matthew Hoare, Masashi Narita
No abstract text is available yet for this article.
October 20, 2016: Cell Cycle
Joon-Ii Jun, Lester F Lau
The expression of Ccn2 (CTGF) has been linked to fibrosis in many tissues and pathologies, although its activities in fibroblastic cells and precise mechanism of action in fibrogenesis are still controversial. Here, we showed that CCN2 can induce cellular senescence in fibroblasts both in vitro and in vivo, whereupon senescent cells express an anti-fibrotic "senescence-associated secretory phenotype" (SASP) that includes upregulation of matrix metalloproteinases and downregulation of collagen. Mechanistically, CCN2 induces fibroblast senescence through integrin α6β1-mediated accumulation of reactive oxygen species, leading to activation of p53 and induction of p16(INK4a)...
October 18, 2016: Journal of Cell Communication and Signaling
Arif U Hasan, Koji Ohmori, Takeshi Hashimoto, Kazuyo Kamitori, Fuminori Yamaguchi, Kumi Konishi, Takahisa Noma, Junsuke Igarashi, Tetsuo Yamashita, Katsuya Hirano, Masaaki Tokuda, Tetsuo Minamino, Akira Nishiyama, Masakazu Kohno
Deterioration of adipocyte function due to increased oxidative stress predisposes patients to metabolic disorders in advanced age. However, the roles of tumor suppressors in such conditions remain largely unknown. Therefore, we aimed to address their dynamics in aged adipocytes using a long-term culture model. We compared 3T3-L1 adipocytes at 17-19 days (long-term) with those at 8-10 days (short-term) after initiation of adipogenic induction for mimicking 'aged' and 'young' adipocytes, respectively. H2O2 release and dihydroethidium (DHE) staining was increased, while superoxide dismutase (SOD) activity was reduced in long-term cultured adipocytes, which is suggestive of enhanced oxidative stress in this group...
October 12, 2016: Biogerontology
Chunya Ni, Marie-Sophie Narzt, Ionela-Mariana Nagelreiter, Cheng Feng Zhang, Lionel Larue, Heidemarie Rossiter, Johannes Grillari, Erwin Tschachler, Florian Gruber
Autophagy is a recycling program which allows cells to adapt to metabolic needs and to stress. Defects in autophagy can affect metabolism, aging, proteostasis and inflammation. Autophagy pathway genes, including autophagy related 7 (Atg7), have been associated with the regulation of skin pigmentation, and autophagy defects disturb the biogenesis and transport of melanosomes in melanocytes as well as transfer and processing of melanin into keratinocytes. We have previously shown that mice whose melanocytes or keratinocytes lack Atg7 (and thus autophagy) as a result of specific gene knockout still retained functioning melanosome synthesis and transfer, and displayed only moderate reduction of pigmentation...
October 9, 2016: International Journal of Biochemistry & Cell Biology
Grasiella Angelina Andriani, Vinnycius Pereira Almeida, Francesca Faggioli, Maurizio Mauro, Wanxia Li Tsai, Laura Santambrogio, Alexander Maslov, Massimo Gadina, Judith Campisi, Jan Vijg, Cristina Montagna
Age-related accumulation of ploidy changes is associated with decreased expression of genes controlling chromosome segregation and cohesin functions. To determine the consequences of whole chromosome instability (W-CIN) we down-regulated the spindle assembly checkpoint component BUB1 and the mitotic cohesin SMC1A, and used four-color-interphase-FISH coupled with BrdU incorporation and analyses of senescence features to reveal the fate of W-CIN cells. We observed significant correlations between levels of not-diploid cells and senescence-associated features (SAFs)...
October 12, 2016: Scientific Reports
Naoko Ishiguro, Haruhiko Yoshida
Alveolar soft part sarcoma is an extremely rare soft tissue sarcoma with poor prognosis. It is characterized by the unbalanced recurrent chromosomal translocation der(17)t(X;17)(p11;q25), resulting in the generation of an ASPL-TFE3 fusion gene. ASPL-TFE3 oncoprotein functions as an aberrant transcriptional factor and is considered to play a crucial role in the tumorigenesis of alveolar soft part sarcoma. However, the underlying molecular mechanisms are poorly understood. In this study, we identified p21 (p21(WAF1/CIP1)) as a direct transcriptional target of ASPL-TFE3...
October 2016: Neoplasia: An International Journal for Oncology Research
Takuya Yoshino, Makoto Sono, Shujiro Yazumi
BACKGROUND: Patients with refractory-ulcerative colitis (UC) require therapy escalation. Sulfasalazine (SASP) could deliver a high concentration of 5-aminosalicylic acid to the colon. The usefulness of SASP for refractory-UC patients, however, is unclear. AIM: The aim was to evaluate the usefulness of SASP for refractory-UC patients. METHOD: We retrospectively analysed 36 (11.4%) of 316 patients with refractory-UC who had been treated with SASP...
2016: BMJ Open Gastroenterology
Hui Wang, Limin Han, Ganye Zhao, Hong Shen, Pengfeng Wang, Zhaomeng Sun, Chenzhong Xu, Yuanyuan Su, Guodong Li, Tanjun Tong, Jun Chen
Senescent cells display a senescence-associated secretory phenotype (SASP) which contributes to tumor suppression, aging, and cancer. However, the underlying mechanisms for SASP regulation are not fully elucidated. SIRT1, a nicotinamide adenosine dinucleotide-dependent deacetylase, plays multiple roles in metabolism, inflammatory response, and longevity, etc. However, its posttranscriptional regulation and its roles in cellular senescence and SASP regulation are still elusive. Here, we identify the RNA-binding protein hnRNP A1 as a posttranscriptional regulator of SIRT1, as well as cell senescence and SASP regulator...
September 9, 2016: Aging Cell
Keisuke Gotanda, Takeshi Hirota, Jumpei Saito, Masato Fukae, Yu Egashira, Noritomo Izumi, Mariko Deguchi, Miyuki Kimura, Shunji Matsuki, Shin Irie, Ichiro Ieiri
A variant in the breast cancer resistance protein (BCRP) gene, 421C> A is a useful biomarker for describing large inter-individual differences in the pharmacokinetics of sulfasalazine (SASP), a BCRP substrate. However, large intra-genotypic variability still exists in spite of the incorporation of this variant into the pharmacokinetics of SASP. Since miR-328 negatively regulates BCRP expression in human tissues, we hypothesized that exosomal miR-328 in plasma, which leaks from the intestines, is a possible biomarker for estimating BCRP activity in the human intestines...
2016: Scientific Reports
Kanad Ghosh, Brian C Capell
Cellular senescence, a state of stable cell cycle arrest in response to cellular stress, is an indispensable mechanism to counter tumorigenesis by halting the proliferation of damaged cells. However, through the secretion of an array of diverse cytokines, chemokines, growth factors, and proteases known as the senescence-associated secretory phenotype (SASP), senescent cells can paradoxically promote carcinogenesis. Consistent with this, removal of senescent cells delays the onset of cancer and prolongs lifespan in vivo, potentially in part through SASP reduction...
August 17, 2016: Journal of Investigative Dermatology
Chinthalapally V Rao, Adam S Asch, Hiroshi Y Yamada
Aneuploidy was predicted to cause cancer. To test the prediction, various Chromosome Instability (CIN) mice models that carry transgenic mutations in mitotic regulators have been created. The availability of these mice has aided researchers in discovering connections between CIN, cancer, and aging. This review will focus on recent interdisciplinary findings regarding how CIN and aneuploidy affect carcinogenesis, immune dysfunction, and aging. High CIN can be generated in vivo by various intrinsic alterations (e...
August 17, 2016: Molecular Carcinogenesis
Agata Michna, Ulrike Schötz, Martin Selmansberger, Horst Zitzelsberger, Kirsten Lauber, Kristian Unger, Julia Hess
BACKGROUND: Acquired and inherent radioresistance of tumor cells is related to tumor relapse and poor prognosis - not only in head and neck squamous cell carcinoma (HNSCC). The underlying molecular mechanisms are largely unknown. Therefore, systemic in-depth analyses are needed to identify key regulators of radioresistance. In the present study, subclones of the CAL-33 HNSCC cell line with different radiosensitivity were analyzed to identify signaling pathways related to the different phenotypes...
2016: Radiation Oncology
Marina Lesina, Sonja Maria Wörmann, Jennifer Morton, Kalliope Nina Diakopoulos, Olga Korneeva, Margit Wimmer, Henrik Einwächter, Jan Sperveslage, Ihsan Ekin Demir, Timo Kehl, Dieter Saur, Bence Sipos, Mathias Heikenwälder, Jörg Manfred Steiner, Timothy Cragin Wang, Owen J Sansom, Roland Michael Schmid, Hana Algül
Tumor suppression that is mediated by oncogene-induced senescence (OIS) is considered to function as a safeguard during development of pancreatic ductal adenocarcinoma (PDAC). However, the mechanisms that regulate OIS in PDAC are poorly understood. Here, we have determined that nuclear RelA reinforces OIS to inhibit carcinogenesis in the Kras mouse model of PDAC. Inactivation of RelA accelerated pancreatic lesion formation in Kras mice by abrogating the senescence-associated secretory phenotype (SASP) gene transcription signature...
August 1, 2016: Journal of Clinical Investigation
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
Ramkumar Menon
Various endocrine, immune, and mechanical factors produced by feto-maternal compartments at term increase intrauterine inflammatory loads to induce labor. The role of fetal (placental) membranes (amniochorion) as providers of parturition signals has not been well investigated. Fetal membranes line the intrauterine cavity and grow with and protect the fetus. Fetal membranes exist as an entity between the mother and fetus and perform unique functions during pregnancy. Membranes undergo a telomere-dependent p38 MAPK-induced senescence and demonstrate a decline in functional and mechanical abilities at term, showing signs of aging...
August 2016: Placenta
Peixiao Tang, Bin Tang, Qing Wang, Kailin Xu, Xinnuo Xiong, Hui Li
The supramolecular interaction between salazosulfapyridine (SASP) and hydroxypropyl-β-cyclodextrin (HP-β-CD), as well as the influence of HP-β-CD on SASP's binding to human serum albumin (HSA), were investigated. Phase-solubility studies indicate that the HP-β-CD/SASP inclusion complex was formed at a 1:1 host-guest stoichiometry with high stability constant. The HP-β-CD/SASP complex, which was characterized by various techniques, exhibited markedly improves aqueous solubility of SASP. The binding of SASP with HSA in the presence and absence of HP-β-CD were investigated...
July 11, 2016: International Journal of Biological Macromolecules
Li Fang, Jian Liu, Lei Wan, Fubing Zhu, Bing Tan, Pingheng Zhang
Objective To observe the effect of Xinfeng capsule (XFC) on miR-155, nuclear factor kappa B (NF-κB) signal pathway, and indexes related to hypercoagulative state in patients with active ankylosing spondylitis (AS), and investigate the possible mechanism. Methods Fifty-six cases in active AS were randomly divided into XFC group and sulfasalazine (SASP) group. All cases in the XFC group took three capsules three times daily for twelve consecutive weeks. The ones in the SASP group took four tablets two times daily for twelve consecutive weeks...
August 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
Tasnuva D Kabir, Ross J Leigh, Hataitip Tasena, Massimiliano Mellone, Ricardo D Coletta, Eric K Parkinson, Stephen S Prime, Gareth J Thomas, Ian C Paterson, Donghui Zhou, John McCall, Paul M Speight, Daniel W Lambert
Senescent cancer-associated fibroblasts (CAF) develop a senescence-associated secretory phenotype (SASP) that is believed to contribute to cancer progression. The mechanisms underlying SASP development are, however, poorly understood. Here we examined the functional role of microRNA in the development of the SASP in normal fibroblasts and CAF. We identified a microRNA, miR-335, up-regulated in the senescent normal fibroblasts and CAF and able to modulate the secretion of SASP factors and induce cancer cell motility in co-cultures, at least in part by suppressing the expression of phosphatase and tensin homologue (PTEN)...
August 2016: Aging
Joshua N Farr, Daniel G Fraser, Haitao Wang, Katharina Jaehn, Mikolaj B Ogrodnik, Megan M Weivoda, Matthew T Drake, Tamara Tchkonia, Nathan K LeBrasseur, James L Kirkland, Lynda F Bonewald, Robert J Pignolo, David G Monroe, Sundeep Khosla
Cellular senescence is a fundamental mechanism by which cells remain metabolically active yet cease dividing and undergo distinct phenotypic alterations, including upregulation of p16(Ink4a) , profound secretome changes, telomere shortening, and decondensation of peri-centromeric satellite DNA. Because senescent cells accumulate in multiple tissues with aging, these cells and the dysfunctional factors they secrete, termed the senescence-associated secretory phenotype (SASP), are increasingly recognized as promising therapeutic targets to prevent age-related degenerative pathologies, including osteoporosis...
June 24, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Francesco Prattichizzo, Valeria De Nigris, Lucia La Sala, Antonio Domenico Procopio, Fabiola Olivieri, Antonio Ceriello
Aging is a complex phenomenon driven by a variety of molecular alterations. A relevant feature of aging is chronic low-grade inflammation, termed "inflammaging." In type 2 diabetes mellitus (T2DM), many elements of aging appear earlier or are overrepresented, including consistent inflammaging. T2DM patients have an increased death rate, associated with an incremented inflammatory score. The source of this inflammation is debated. Recently, the senescence-associated secretory phenotype (SASP) has been proposed as the main origin of inflammaging in both aging and T2DM...
2016: Oxidative Medicine and Cellular Longevity
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