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Meiqing Liu, Hening Li, Qun Zhou, Hong Zhao, Deguan Lv, Jiangang Cao, Jinyong Jiang, Mingzhu Tang, Di Wu, Jiaqi Liu, Lele Wu, Haoliang Hu, Lu He, Shifang Huang, Zhe Chen, Lanfang Li, Linxi Chen
Apelin is the endogenous ligand of APJ receptor. Both monocytes (MCs) and human umbilical vein endothelial cells (HUVECs) express apelin and APJ, which play important roles in the physiological processes of atherosclerosis. Our previous research indicated that apelin-13 promoted MCs-HUVECs adhesion. Here, we further explore the mechanism responsible for MCs-HUVECs adhesion induced by apelin-13. Apelin-13 promoted reactive oxygen species (ROS) generation and NOX4 expression in HUVECs. Apelin-13 inducedautophagy, increased proteins beclin1 and LC3-II/I expression and induced autophagy flux in HUVECs, which was blocked by NAC, catalase and DPI...
April 24, 2018: Journal of Cellular Physiology
Li Zhu, Xiuping Liu, Dongmei Li, Shuhong Sun, Yue Wang, Xianghong Sun
BACKGROUND: Ovarian cancer is one of the most prevalent gynecological malignancies and thus the development of novel therapeutic agents for managing ovarian cancer is imperative. Euxanthone, a xanthone derived from Polygala caudata, has been found to exert cytotoxic effects on cancerous cells. This study was designed to assess the role of euxanthone in ovarian cancer. METHODS AND MATERIALS: Cell Counting Kit-8 (CCK-8) assay was utilized to assess the viability of human ovarian cancer SKOV3 and OVCAR3 cell lines...
April 19, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Jing Wang, Li Long, Yongzheng Chen, Yingshu Xu, Lei Zhang
To overcome cancer drug resistance, in present study, a series of podophyllotoxin-indirubin hybrids were designed, synthesized, and evaluated for anticancer efficacy against two human chronic myeloid leukemia cell cultures. Among them, compound Da-1 was the most potent in resistent K562/VCR cells with an IC50 value of 0.076 ± 0.008 μM. Preliminary mechanism studies showed that Da-1 significantly induced apoptosis and cell cycle arrest at the G2 phase. Decrease in mitochondrial membrane potential, accompanied by activated PARP cleavage, was observed in K562/VCR cells after incubation with Da-1...
April 10, 2018: Bioorganic & Medicinal Chemistry Letters
Yong Chul Jang, Dong Joo Hwang, Jung Hoon Koo, Hyun Seob Um, Nam Hee Lee, Dong Cheol Yeom, Youngil Lee, Joon Yong Cho
PURPOSE: We investigated whether treadmill exercise (TE)-induced neuroprotection was associated with enhanced autophagy and reduced apoptosis in a mouse model of pharmacologically induced Parkinson's disease (PD). METHODS: PD was induced via the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). C57BL/6 male mice were randomly assigned to the following three groups: control (C57BL, n=10), MPTP with probenecid (MPTP/C, n=10), and MPTP/ C plus exercise (MPTP-TE, n=10)...
March 30, 2018: Journal of Exercise Nutrition & Biochemistry
Pablo Garnica, Ignacio Encío, Daniel Plano, Juan A Palop, Carmen Sanmartín
A series of 16 new diselenide-acylselenourea conjugates have been designed following the fragment-based drug strategy. Compound in vitro cytotoxic potential was evaluated against six human cancer cell lines and two nonmalignant derived cell lines with the aim of determining their potency and selectivity. Nine derivatives exhibited GI50 values under 10 μM in at least four cancer cell lines. A clear gap situated phenyl substitution over heterocyclic moieties in terms of selectivity. Among carbocyclic compounds, derivatives 2 and 7 significantly inhibited cell growth of breast adenocarcinoma cells with GI50 values of 1...
April 12, 2018: ACS Medicinal Chemistry Letters
Xiaolu Duan, Zhenzhen Kong, Xin Mai, Yu Lan, Yang Liu, Zhou Yang, Zhijian Zhao, Tuo Deng, Tao Zeng, Chao Cai, Shujue Li, Wen Zhong, Wenqi Wu, Guohua Zeng
Hyperoxaluria-induced oxidative injury of renal tubular epithelial cell is a casual and essential factor in kidney calcium oxalate (CaOx) stone formation. Autophagy has been shown to be critical for the regulation of oxidative stress-induced renal tubular injury; however, little is known about its role in kidney CaOx stone formation. In the present study, we found that the autophagy antagonist chloroquine could significantly attenuate oxalate-induced autophagy activation, oxidative injury and mitochondrial damage of renal tubular cells in vitro and in vivo, as well as hyperoxaluria-induced CaOx crystals depositions in rat kidney, whereas the autophagy agonist rapamycin exerted contrasting effects...
June 2018: Redox Biology
Fan Yang, Jianzhao Liao, Ruonan Pei, Wenlan Yu, Qingyue Han, Ying Li, Jianying Guo, Lianmei Hu, Jiaqiang Pan, Zhaoxin Tang
Copper (Cu) is an essential trace element that is required for the catalysis of several cellular enzymes. Excessive Cu could induce hepatotoxicity in humans and multiple animals. The purpose of this study was to investigate the effects of autophagy machinery on Cu-induced hepatotoxicity. Chicken hepatocytes were cultured in medium in the absence and presence of Cu sulfate (CuSO4 ) (0, 10, 50, and 100 μM) for 0, 6, 12, and 24 h, and in the combination of CuSO4 and N-acetyl-l-cysteine (NAC) (1 mM), rapamycin (10 nM), and 3-methyladenine (3-MA) (5 mM) for 24 h...
March 29, 2018: Chemosphere
Nina Brandt, Thomas P Gunnarsson, Jens Bangsbo, Henriette Pilegaard
Moderately trained male subjects (mean age 25 years; range 19-33 years) completed an 8-week exercise training intervention consisting of continuous moderate cycling at 157 ± 20 W for 60 min (MOD; n = 6) or continuous moderate cycling (157 ± 20 W) interspersed by 30-sec sprints (473 ± 79 W) every 10 min (SPRINT; n = 6) 3 days per week. Sprints were followed by 3:24 min at 102 ± 17 W to match the total work between protocols. A muscle biopsy was obtained before, immediately and 2 h after the first training session as well as at rest after the training session...
April 2018: Physiological Reports
Qiuhui Yao, Min Feng, Bo Yang, Zhimin Long, Shifang Luo, Min Luo, Guiqiong He, Kejian Wang
Epidemiologic studies have demonstrated that women account for two-thirds of Alzheimer's disease (AD) cases, for which the decline in circulating gonadal hormone is considered to be one of the major risk factors. In addition, ovarian hormone deficiency may affect β-amyloid (Aβ) deposition, which has a close relationship with autophagic flux. In this study, we investigated the impact of short-term or long-term ovarian hormone deprivation on two mouse models, the non-transgenic (wild-type) and the APP/PS1 double-transgenic AD (2×TgAD) model...
March 29, 2018: Acta Biochimica et Biophysica Sinica
Dolors Puigoriol-Illamola, Christian Griñán-Ferré, Foteini Vasilopoulou, Rosana Leiva, Santiago Vázquez, Mercè Pallàs
Elevated glucocorticoid (GC) exposure is widely accepted as a key factor in the age-related cognitive decline in rodents and humans. 11β-HSD1 is a key enzyme in the GCs pathway, catalyzing the conversion of 11β-dehydrocorticosterone to corticosterone in mice, with possible implications in neurodegenerative processes and cognitive impairment. Here, we determined the effect of a new 11β-HSD1 inhibitor, RL-118, administered to 12-month-old senescence-accelerated mouse-prone 8 (SAMP8) mice with neuropathological AD-like hallmarks and widely used as a rodent model of cognitive dysfunction...
April 2, 2018: Molecular Neurobiology
Mohadeseh Hasanpourghadi, Nazia Abdul Majid, Mohd Rais Mustafa
We recently reported that methyl 2-(-5-fluoro-2-hydroxyphenyl)-1H-benzo[d]imidazole-5-carboxylate (MBIC) is a microtubule targeting agent (MTA) with multiple mechanisms of action including apoptosis in two human breast cancer cell-lines MCF-7 and MDA-MB-231. In the present study, investigation of early molecular events following MBIC treatment demonstrated the induction of autophagy. This early (< 24 h) response to MBIC was characterized by accumulation of autophagy markers; LC3-II, Beclin1, autophagic proteins (ATGs) and collection of autophagosomes but with different variations in the two cell-lines...
March 30, 2018: Biochemical Pharmacology
Carmela Fusco, Barbara Mandriani, Martina Di Rienzo, Lucia Micale, Natascia Malerba, Dario Cocciadiferro, Eva Sjøttem, Bartolomeo Augello, Gabriella Squeo, Maria Teresa Pellico, Ashish Jain, Terje Johansen, Gian Maria Fimia, Giuseppe Merla
Autophagy is a catabolic process needed for maintaining cell viability and homeostasis in response to numerous stress conditions. Emerging evidence indicates that the ubiquitin system has a major role in this process. TRIMs, an E3 ligase protein family, contribute to selective autophagy acting as receptors and regulators of the autophagy proteins recognizing endogenous or exogenous targets through intermediary autophagic tags, such as ubiquitin. Here we report that TRIM50 fosters the initiation phase of starvation-induced autophagy and associates with Beclin1, a central component of autophagy initiation complexes...
March 28, 2018: Biochimica et Biophysica Acta
Qiu-Li Zhai, Xiang-Dan Hu, Jing Xiao, Dong-Qing Yu
This study aimed to investigate the possible sensitivity of Astragalus polysaccharides, in order to improve the chemosensitivity of cervical cancer HeLa cells to cisplatin by regulating the cell autophagy, and explore its possible mechanism. In this study, HeLa cells were divided into control group, cisplatin group, Astragalus polysaccharide group, and Astragalus polysaccharide combined with cisplatin group. MTT assay was used to detect the proliferation of cervical cancer HeLa cells. Flow cytometry was used to detect the apoptosis and cycle of HeLa cells in each experimental group...
February 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Sei Sai, Masao Suzuki, Eun Ho Kim, Mitsuhiro Hayashi, Guillaume Vares, Naoyoshi Yamamoto, Tadaaki Miyamoto
Malignant mesothelioma (MM) is extremely aggressive and a typical refractory cancer. In this study we investigated how effective on killing MM cells by carbon ion beam alone or in combination with cisplatin (CDDP) in vitro . Carbon ion beam (at the center of SOBP with 50 keV/µm of average LET) dose-independently suppressed MM cells MESO-1 and H226 cell viability and in combination with CDDP (25 μM) significantly enhanced its action. Relative biological effectiveness (RBE) values at 73 keV/μm and 13 keV/μm portion of carbon ion beam was estimated as 2...
March 13, 2018: Oncotarget
Fangfang Li, Changwei Zhang, Yinzi Li, Guanwei Wu, Xilin Hou, Xueping Zhou, Aiming Wang
Autophagy emerges as an essential immunity defense against intracellular pathogens. Here we report that turnip mosaic virus (TuMV) infection activates autophagy in plants and that Beclin1 (ATG6), a core component of autophagy, inhibits virus replication. Beclin1 interacts with NIb, the RNA-dependent RNA polymerase (RdRp) of TuMV, via the highly conserved GDD motif and the interaction complex is targeted for autophagic degradation likely through the adaptor protein ATG8a. Beclin1-mediated NIb degradation is inhibited by autophagy inhibitors...
March 28, 2018: Nature Communications
Abhishek Vats, Mandaville Gourie-Devi, Kavita Ahuja, Ankkita Sharma, Saima Wajid, Nirmal Kumar Ganguly, Vibha Taneja
Misfolded protein aggregates are the hallmark of Amyotrophic Lateral Sclerosis (ALS) which suggests involvement of protein homeostasis pathways in etiology of ALS. However, status of protein homeostasis in peripheral blood of ALS is not well established. We analyzed expression levels of key genes of proteostasis pathways in peripheral blood mononuclear cells (PBMCs) of sporadic ALS (sALS) patients and healthy controls. Increased protein carbonylation was observed in patients reflecting oxidative damage in PBMCs...
April 15, 2018: Journal of the Neurological Sciences
Chunxiao Zhang, Xiuyuan Yu, Jiahao Gao, Qianqian Zhang, Shuqiang Sun, Hua Zhu, Xinjun Yang, Hongtao Yan
Hematotoxicity of benzene is derived mainly from its active metabolite, 1,4-Benzoquinone (1,4-BQ), which induces cell apoptosis and mitochondrial damage. Damaged mitochondria are degraded through a specialized autophagy pathway, called mitophagy, which is driven by PINK1/Parkin signaling. However, whether mitophagy is involved in 1,4-BQ-induced toxicity remains unclear. This study was designed to investigate whether PINK1/Parkin-mediated mitophagy is activated in 1,4-BQ-treated HL-60 cells, and the roles mitophagy plays in 1,4-BQ-induced apoptosis...
March 20, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Yongchul Jang, Insu Kwon, Wankeun Song, Ludmila M Cosio-Lima, Youngil Lee
Parkinson's disease (PD) is a neurodegenerative disorder caused by loss of dopaminergic neurons in the substantia nigra, leading to motor dysfunction. Growing evidence has demonstrated that endurance exercise (EE) confers neuroprotection against PD; However, the exact molecular mechanisms responsible for exercise-induced protection of dopaminergic neurons in PD remain unclear. Since oxidative stress plays a key role in the degenerative process of PD. We investigated whether EE-induced neuroprotection is associated with enhanced antioxidative capacity and autophagy, using a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration...
March 17, 2018: Neuroscience
Dongjia Lin, Yan Gao, Luodan Zhao, Yanhuo Chen, Shaofeng An, Zhixiang Peng
Enterococcus faecalis (E. faecalis) infection is considered an important etiological factor for the development of persistent apical periodontitis (PAP), but the exact mechanisms of autophagy between E. faecalis and immune cells remain unknown. In this study, we elucidated how E. faecalis lipoteichoic acid (LTA) is associated with macrophages autophagy. We found that E. faecalis LTA apparently activated macrophage autophagy with significant increase of autophagosomes and autophagy relative protein. Meanwhile, we noticed significantly decreasing expression of p-Akt and p-mTOR...
March 15, 2018: Biochemical and Biophysical Research Communications
Myosotys Rodriguez, Jessica Lapierre, Chet Raj Ojha, Ajeet Kaushik, Elena Batrakova, Fatah Kashanchi, Seth M Dever, Madhavan Nair, Nazira El-Hage
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
March 14, 2018: Scientific Reports
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