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Verica Paunovic, Irena Vukovic Petrovic, Marina Milenkovic, Kristina Janjetovic, Vera Pravica, Irena Dujmovic, Emina Milosevic, Vanja Martinovic, Sarlota Mesaros, Jelena Drulovic, Vladimir Trajkovic
Autophagy, a process of controlled self-digestion which regulates cell homeostasis, is involved in innate and adaptive immunity. We investigated the expression of autophagy genes and autophagic activity in distinct lymphocyte populations in treatment-naive MS patients. The mRNA and protein levels of autophagy-related (ATG)5, required for autophagosome formation, were increased in CD4+ and CD4- T cells, but not B cells of MS patients compared to control subjects. The expression of other investigated autophagy genes, as well as the autophagic activity, did not significantly differ between the two groups...
March 5, 2018: Journal of Neuroimmunology
Xi Wu, Xue Xue, Lihui Wang, Wenjing Wang, Jian Han, Xiaoxue Sun, Haotian Zhang, Yueyang Liu, Xiaohang Che, Jingyu Yang, Chunfu Wu
Autophagy, a cellular survival mechanism, is thought to allow the recycling of cellular breakdown products when cancer cells are subjected to chemotherapy, thus decreasing drug-induced apoptosis. Disulfiram (DSF), a drug widely used to control alcoholism, possesses anticancer activity by inducing apoptosis in vitro and in vivo in a copper (Cu)-dependent manner. Our previous studies proved that DSF/Cu exerts increased anti-tumor effects on non-small cell lung cancer (NSCLC) xenograft models, and inhibits NSCLC recurrence driven by ALDH-positive cancer stem cells...
March 13, 2018: European Journal of Pharmacology
Yuan Chen, Kai Leonie Schnitzler, Yunxia Ma, Miljana Nenkov, Bernhard Theis, Iver Petersen
Exploitation of autophagy might potentially improve therapeutic strategy. Here, we analyzed the protein expression of autophagy-associated genes including LC3A, LC3B, Beclin-1, p62, and Atg5 in 88-131 primary lung tumors by immunohistochemistry (IHC) on tissue-microarrays (TMAs). Additionally, the DNA methylation pattern of LC3A was investigated by bisulfite sequencing (BS) and methylation-specific-PCR (MSP). It turned out that the higher expression of LC3A protein was associated with adenocarcinoma compared to squamous cell carcinoma of lung ( p = 0...
2018: Disease Markers
Dengfeng Ding, Shiyuan Xu, Hongfei Zhang, Wei Zhao, Xueping Zhang, Yuanxu Jiang, Ping Wang, Zhongliang Dai, Junzhi Zhang
The aim of the present study was to investigate the effects of 3-methyladenine (3-MA) and dexmedetomidine (DEX) pretreatment on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and the potential mechanism underlying the effects. LPS was instilled into the trachea of BALB/c mice to induce the ALI model. Solutions of 3-MA or DEX were intravenously injected into the mice 1 h later to establish the 3-MA and DEX groups. On days 1, 3 and 5 after the injections, arterial blood gas analysis was conducted, and the lung wet-dry weight ratio (W/D) was determined...
April 2018: Experimental and Therapeutic Medicine
Li Wang, Yang Li, Na Ning, Jin Wang, Zi Yan, Suli Zhang, Xiangying Jiao, Xiaohui Wang, Huirong Liu
It has been recognized that myocardial apoptosis is one major factor in the development of heart dysfunction and autophagy has been shown to influence the apoptosis. In previous studies, we reported that anti-β1 -adrenergic receptor autoantibodies (β1 -AABs) decreased myocardial autophagy, but the role of decreased autophagy in cardiomyocyte apoptosis remains unclear. In the present study, we used a β1 -AAB-immunized rat model to investigate the role of decreased autophagy in cardiomyocyte apoptosis. We reported that the level of autophagic flux increased early and then decreased in an actively β1 -AAB-immunized rat model...
March 14, 2018: Cell Death & Disease
Yumao Jiang, Yue Jiao, Yang Liu, Meiyu Zhang, Zhiguo Wang, Yujuan Li, Tao Li, Xiaoliang Zhao, Danqiao Wang
As shown in our previous study, sinomenine hydrochloride (SH), the major bioactive alkaloid isolated from Sinomenium acutum Rehd. et Wils. (Fam. Menispermaceae ), initiates the autophagy-mediated death of human glioblastoma cells by generating reactive oxygen species and activating the autophagy-lysosome pathway. However, its effects on the migration and invasion of human glioblastoma cells have not yet been elucidated. Therefore, human glioblastoma U87 and SF767 cells were treated with SH (0.125 and 0.25 mM) for 24 h, and cell migration and invasion were assessed using scratch wound healing, migration and invasion assays...
March 14, 2018: International Journal of Molecular Sciences
Jun Ma, Yiping Jia, Bingyan Liu, Shaoqiu Wu, Yan Cao, Xianjun Sun, Xiang Yin, Mingyi Shang, Aiwu Mao
Cholangiocarcinoma (CCA) is a lethal cancer associated with chronic inflammation that has increased in prevalence in recent decades. The dysregulated expression of microRNAs (miRNAs) has been detected in various types of malignancies, and depending on the target genes this can result in miRNAs functioning as tumor suppressors or oncogenes. In this study, we investigated the role of miR-124 in cholangiocarcinoma (CCA) and found that its expression was significantly downregulated in the tumor tissue of patients and in CCA cell lines...
March 9, 2018: Experimental Cell Research
Hong-Ying Chu, Xue Chen, Yu-E Jiang, Wei Wang, Xiao Qi, Zhao-Ming Zhong, Mu-Sheng Zeng, Xiao-Feng Zhu, Chuan-Zheng Sun
The role of autophagy in tongue squamous cell carcinoma (TSCC) cisplatin resistance is unclear. We aimed to identify a possible synergistic effect of autophagy inhibitors and cisplatin in TSCC cells and explore the underlying mechanism. Our results indicate that autophagic flux was high in TSCC cells; Autophagy inhibitor bafilomycin A1 increased cisplatin cytotoxicity in TSCC cells by inhibiting lysosomal uptake of platinum and enhancing intracellular platinum ion binding to DNA; Autophagy gene (Atg5) knockout in TSCC cells did not duplicate the above-mentioned sensitization of bafilomycin A1...
March 7, 2018: Cancer Letters
Xu Yang, Jian Zhang, Qiang Ji, Fan Wang, Miao Song, Yanfei Li
Aluminum (Al) exposure has adverse effects on osteoblasts, and the effect might be through autophagy-associated apoptosis. In this study, we showed that aluminum trichloride (AlCl3 ) could induce autophagy in MC3T3-E1 cells, as demonstrated by monodansylcadaverine (MDC) staining and the expressions of the ATG3, ATG5, and ATG9 genes. We found AlCl3 inhibited MC3T3-E1 cell survival rate and caused apoptosis, as evidenced by CCK-8 assay, Annexin V/PI double staining, and increased expressions of Bcl-2, Bax, and Caspase-3 genes...
March 8, 2018: Biological Trace Element Research
Leonardo Iula, Irene A Keitelman, Florencia Sabbione, Federico Fuentes, Mauricio Guzman, Jeremías Gastón Galletti, Pehuén Pereyra Gerber, Matías Ostrowski, Jorge R Geffner, Carolina C Jancic, Analía S Trevani
Interleukin-1β (IL-1β), a major pro-inflammatory cytokine, is a leaderless cytosolic protein whose secretion does not follow the classical endoplasmic reticulum-to-Golgi pathway, and for which a canonical mechanism of secretion remains to be established. Neutrophils are essential players against bacterial and fungi infections. These cells are rapidly and massively recruited from the circulation into infected tissues and, beyond of displaying an impressive arsenal of toxic weapons effective to kill pathogens, are also an important source of IL-1β in infectious conditions...
2018: Frontiers in Immunology
Shumin Ding, Xuefeng Hou, Gang Wang, Huihui Qiu, Ying Liu, Yuanli Zhou, Mei Du, Xiaobin Tan, Jie Song, Yingjie Wei, Luan Shu, Zhiyong Li, Liang Feng, Xiaobin Jia
Excessive autophagy plays a crucial role in cigarette smoking extract (CSE)-induced inflammation response and oxidative damage of respiratory epithelial cells. The components from Eclipta prostrata L. (CCE) have been shown to be beneficial for CSE-induced epithelial cells injury. However, whether its protection on CSE-stress injury is related to its regulation on autophagy remains still unclear. In this study, CCE, containing mainly wedelolactone of 45.88% and demethylwedelolactone of 23.74%, could improve significantly 10%CSE-induced cell viability of normal human bronchial epithelial (NHBE) cells using CCK-8 kit...
2018: Frontiers in Pharmacology
Jianhua Chen, Lemeng Zhang, Hui Zhou, Wei Wang, Yongzhong Luo, Hua Yang, Huihuang Yi
Recent studies have indicated that autophagy contributes to tumorigenesis and participates in acquired chemotherapeutic resistance. The present study aimed to determine the function and underlying mechanism of cisplatin‑induced autophagy in A549 human lung cancer cells. Autophagy was measured by LC3B‑I/II conversion, LC3B puncta and autophagosomes formation. Apoptotic cell death was measured by caspase‑3 activity, caspase‑3 cleavage and LDH release. The transcriptional and expressional level of autophagy related proteins were measured by reverse transcription-quantitative polymerase chain reaction and western blot analysis...
March 6, 2018: Molecular Medicine Reports
Jiaqi Chu, Yuanyuan Fu, Jiecheng Xu, Xueping Zheng, Qianqian Gu, Xia Luo, Qi Dai, Shuxian Zhang, Peiqing Liu, Liang Hong, Min Li
Atg4 is essential for autophagosome formation and Atg8 recycle with the function of processing the precursor and the lipidated Atg8-family proteins. Abnormal autophagic activity is involved in a variety of pathophysiological diseases and ATG4B is of interest as a potential therapeutic target due to its key roles in autophagy process. So ATG4B inhibitors are highly needed. FMK-9a is the most potent inhibitor reported so far. In this study, we confirmed FMK-9a could suppress ATG4B activity in vitro and in cells, with an IC50 of 260 nM...
March 3, 2018: Archives of Biochemistry and Biophysics
Bing-Xin Chu, Rui-Feng Fan, Shu-Qian Lin, Du-Bao Yang, Zhen-Yong Wang, Lin Wang
Autophagy and apoptosis are two different biological processes that determine cell fates. We previously reported that autophagy inhibition and apoptosis induction are involved in lead(II)-induced cytotoxicity in primary rat proximal tubular (rPT) cells, but the interplay between them remains to be elucidated. Firstly, data showed that lead(II)-induced elevation of LC3-II protein levels can be significantly modulated by 3-methyladenine or rapamycin; moreover, protein levels of Autophagy-related protein 5 (Atg5) and Beclin-1 were markedly up-regulated by lead(II) treatment, demonstrating that lead(II) could promote the autophagosomes formation in rPT cells...
February 24, 2018: Journal of Inorganic Biochemistry
Xuemei Wan, Jeffrey D Serrill, Ian R Humphreys, Michelle Tan, Kerry L McPhail, Ian G Ganley, Jane E Ishmael
Our understanding of autophagy and lysosomal function has been greatly enhanced by the discovery of natural product structures that can serve as chemical probes to reveal new patterns of signal transduction in cells. Coibamide A is a cytotoxic marine natural product that induces mTOR-independent autophagy as an adaptive stress response that precedes cell death. Autophagy-related (ATG) protein 5 (ATG5) is required for coibamide-induced autophagy but not required for coibamide-induced apoptosis. Using wild-type and autophagy-deficient mouse embryonic fibroblasts (MEFs) we demonstrate that coibamide-induced toxicity is delayed in ATG5-/- cells relative to ATG5+/+ cells...
March 1, 2018: Marine Drugs
Ajda Coker Gurkan, Elif Damla Arisan, Pinar Obakan Yerlikaya, Halime Ilhan, Narcin Palavan Unsal
PURPOSE: One of the recently developed polyamine (PA) analogues, N1 ,N11 -diethylnorspermine (DENSpm), has been found to act as an apoptotic inducer in melanoma, breast, prostate and colon cancer cells. Also, its potential to induce autophagy has been established. Unfolded protein responses and starvation of amino acids are known to trigger autophagy. As yet, however, the molecular mechanism underlying PA deficiency-induced autophagy is not fully clarified. Here, we aimed to determine the apoptotic effect of DENSpm after autophagy inhibition by 3-methyladenine (3-MA) or siRNA-mediated Beclin-1 silencing in colon cancer cells...
February 28, 2018: Cellular Oncology (Dordrecht)
Oyuna S Kozhevnikova, Darya V Telegina, Vasiliy A Devyatkin, Nataliya G Kolosova
Age-related macular degeneration (AMD) is a complex neurodegenerative disease resulting in a loss of central vision in the elderly. It is currently assumed that impairment of autophagy may be one of the key mechanisms leading to AMD. Here we estimated the influence of age-related autophagy alterations in the retina on the development of AMD-like retinopathy in senescence-accelerated OXYS rats. Significant changes in the expression of the autophagy proteins were absent at the age preceding the development of retinopathy (age 20 days)...
February 28, 2018: Biogerontology
Yue-Yue Zhang, Man Yang, Jin-Fang Bao, Li-Jie Gu, Hong-Lei Yu, Wei-Jie Yuan
BACKGROUND: Accelerated muscle atrophy is associated with a three-fold increase in mortality in chronic kidney disease (CKD) patients. It is suggested that hyperphosphatemia might contribute to muscle wasting, but the underlying mechanisms remain unclear. Although evidence indicates that autophagy is involved in the maintenance of muscle homeostasis, it is not known if high phosphate levels can result in activation of autophagy, leading to muscle protein loss. METHODS: Immortalized rat L6 myotubes were exposed to a high concentration of phosphate, with or without autophagy inhibition...
February 27, 2018: BMC Nephrology
Jiangang Liu, Yingru Xing, Ling Rong
A number of miRNAs have been found to be abnormally expressed or mutated in numerous cancers and thus, are considered to act as oncogenes or tumor suppressor genes. The aim of the present study was to investigate the effect of miR-181 on cisplatin-resistant non-small cell lung cancer (NSCLC). In patients with cisplatin-resistant NSCLC, miR-181 expression was found to be markedly decreased. In addition, in the cisplatin-resistant human lung adenocarcinoma cell line A549/DDP, miR-181 downregulation promoted cell growth and metastasis and inhibited cell apoptosis, whereas miR-181 overexpression exerted the opposite effects...
February 13, 2018: Oncology Reports
Grant R Campbell, Rachel S Bruckman, Shayna D Herns, Shweta Joshi, Donald Durden, Stephen A Spector
In this study, we investigated the effect of the dual phosphatidylinositol 3-kinase/mechanistic target of rapamycin (PI3K/MTOR) inhibitor dactolisib (NVP-BEZ235), the PI3K/ MTOR/bromodomain-containing protein 4 (BRD4) inhibitor SF2523 and the BET inhibitor JQ1 on the productive infection of primary macrophages with human immunodeficiency type-1 (HIV). These inhibitors did not alter the initial susceptibility of macrophages to HIV infection. However, dactolisib, JQ1 and SF2523 all decreased HIV replication in macrophages in a dose dependent manner via degradation of intracellular HIV through autophagy...
February 23, 2018: Journal of Biological Chemistry
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