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Jilong Zhou, Chengyu Li, Wang Yao, Alsiddig M A, Lijun Huo, Honglin Liu, Yi-Liang Miao
Autophagy is an essential cellular mechanism that degrades cytoplasmic proteins and organelles to recycle their components. Here we showed that autophagy was essential for the glycolysis switch and energy homeostasis in mouse granulosa cells (MGCs) under hypoxic condition. Our data indicated that hypoxia inducible factor-1α (HIF-1α) could be largely increased in developing follicles and this remarkable upregulation of HIF-1α triggered cell autophagy and glucose uptake. We found that blocking autophagy by Atg7 knockdown and 3-methyladenine (3-MA) treatment affected the glucose metabolism, with increased glycolytic enzyme activity and decreased ATP production...
March 13, 2018: Biology of Reproduction
Qiujun Liu, Xianyao Zhou, Chuan Li, Xuemei Zhang, Chang Long Li
There is limited knowledge regarding the influence of autophagy on the anticancer effect of dihydroartemisinin (DHA). The present study aimed to investigate this influence within human breast cancer cells. Changes in cell viability, cell cycle distribution, apoptosis and associated genes were analyzed in MDA-MB-231 cells subjected to DHA following alteration in autophagy levels; the autophagy level was decreased following autophagy-related 7 (Atg7) knockdown or increased using rapamycin. The data indicated that rapamycin had the ability to notably enhance the anticancer effect of DHA on MDA-MB-231 cells...
April 2018: Oncology Letters
Jing Sun, Yarong Mu, Yuanyuan Jiang, Ruilong Song, Jianxin Yi, Jingsong Zhou, Jun Sun, Xinan Jiao, Richard A Prinz, Yi Li, Xiulong Xu
Autophagy plays a central role in degrading misfolded proteins such as mutated superoxide dismutase 1 (SOD1), which forms aggregates in motor neurons and is involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). Autophagy is activated when UNC-51-like kinase 1 (ULK1) is phosphorylated at S555 and activated by AMP-activated protein kinase (AMPK). Autophagy is suppressed when ULK1 is phosphorylated at S757 by the mechanistic target of rapamycin (mTOR). Whether p70 S6 kinase 1 (S6K1), a serine/threonine kinase downstream of mTOR, can also regulate autophagy remains uncertain...
March 14, 2018: Cell Death & Disease
Keiji Kuba
Cardiovascular diseases are major increasing causes of death in developed countries. Coordinated transcriptional and post-transcriptional regulation of gene expression is crucial to maintain normal heart physiology. Dysregulation of these processes causes and/or accompanies multiple pathologies, such as cardiomyopathy and myocardial infarction. The exonuclease-mediated shortening of the mRNA poly(A) tail, a process called deadenylation, is a key step in regulated mRNA degradation, and deadenylation is mostly executed by the CCR4-NOT complex...
2018: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
Lunming Liu, Weifeng Shen, Zhihui Zhu, Jinxiong Lin, Qingxia Fang, Yeping Ruan, Huajun Zhao
Fulvestrant is the FDA-approved "pure anti-estrogen" agent for malignant breast cancer therapy. But endocrine resistance causes drug failure. A new approach is desired for fulvestrant-resistant breast cancer (FRBC) therapy. This study aims to find an effective approach to inhibit FRBC for patients with advanced breast cancer. MTT assay was first performed to detect the effect of inhibitors of c-ABL (imatinib) and EGFR (lapatinib) on FRBC cells. Microarray analysis was carried out to identify microRNA which is significantly changed between parental and FRBC cells...
March 6, 2018: Biochemical and Biophysical Research Communications
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
Deng Qian, Liang Liang, Liu Quanhai, Duan Wanli, Jiang Yazhuo, Zhang Liandong
The aim of this study was to explore the effects of curcumin on renal cell carcinoma(RCC) through regulating autophagy. Cell viabilities were determined by MTT assay in RCC cells after treatment with curcumin at different concentrations for various durations. ATG7 silencing RCC cells were established to test the role of autophagy. The levels of key proteins on autophagy pathway were analyzed by Western blot. We found out that following 24h curcumin treatment, the viability of RCC cells had an increase at 5μM and no significant change at 20μM but a decrease at 80μM...
March 1, 2018: European Journal of Pharmacology
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
Javad Alizadeh, Aleksandra Glogowska, James Thliveris, Forouh Kalantari, Shahla Shojaei, Sabine Hombach-Klonisch, Thomas Klonisch, Saeid Ghavami
Lung cancer is considered one of the most frequent causes of cancer-related death worldwide and Non-Small Cell Lung Cancer (NSCLC) accounts for 80% of all lung cancer cases. Autophagy is a cellular process responsible for the recycling of damaged organelles and protein aggregates. Transforming growth factor beta-1 (TGFβ1 ) is involved in Epithelial to Mesenchymal Transition (EMT) and autophagy induction in different cancer models and plays an important role in the pathogenesis of NSCLC. It is not clear how autophagy can regulate EMT in NSCLC cells...
February 23, 2018: Biochimica et Biophysica Acta
Jing Liu, Man J Livingston, Guie Dong, Chengyuan Tang, Yunchao Su, Guangyu Wu, Xiao-Ming Yin, Zheng Dong
Histone deacetylase inhibitors (HDACi) have therapeutic effects in models of various renal diseases including acute kidney injury (AKI); however, the underlying mechanism remains unclear. Here we demonstrate that two widely tested HDACi (suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA)) protect the kidneys in cisplatin-induced AKI by enhancing autophagy. In cultured renal proximal tubular cells, SAHA and TSA enhanced autophagy during cisplatin treatment. We further verified the protective effect of TSA against cisplatin-induced apoptosis in these cells...
February 23, 2018: Cell Death & Disease
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
Wei He, Aiqing Zhang, Lei Qi, Chen Na, Rui Jiang, Zhining Fan, Jianping Chen
BACKGROUND/AIMS: Autophagy is an evolutionarily conserved catabolic mechanism to maintain energy homeostasis and to remove damaged cellular components, which plays an important role in the survival of various cells. Inhibiting autophagy is often applied as a new strategy to halt the growth of cancer cells. METHODS: The effect of FOXO1 gene on cellular function and apoptosis and its underlying mechanisms were investigated in cultured QBC939 cells by the methylthiazoletetrazolium (MTT) assay, western blot, DCFDA mitochondrial membrane potential, and ATP content measurement...
February 16, 2018: Cellular Physiology and Biochemistry
Zhiping Fu, Cheng Xi, Jie Kuang, Haoran Feng, Lingxie Chen, Juyong Liang, Xiaonan Shen, Stanley Yuen, Peng Chenghong, Shen Baiyong, Jin Zhijian, Weihua Qiu
As an established anti-cancer drug, gemcitabine (GEM) is an effective systemic treatment for advanced pancreatic cancer (PC). However, little is known about the potential effectors that may modify tumour cell sensitivity towards GEM. Autophagy, as a physiological cellular mechanism, is involved in both cell survival and cell death. In this study, we found that exposure to GEM induced a significant increase in autophagy in a dose-dependent manner in PANC-1 and BxPC-3 cells. Inhibition of autophagy by chloroquine (CQ) and ATG7 siRNA increased GEM-induced cytotoxicity, and CQ was more effective than ATG7 siRNA...
February 17, 2018: Molecular Oncology
Changmeng Xu, Mi Wang, Zhongbao Song, Zhijian Wang, Qianyu Liu, Ping Jiang, Juan Bai, Yufeng Li, Xianwei Wang
Autophagy of cytoplasmic components plays an essential role in the pathogenic infection process. Furthermore, research suggests that autophagy is an extremely important component of the innate immune response. Our study aimed to reveal the effect of virus-induced autophagy on pseudorabies virus (PRV) replication. Our results confirmed that light chain 3 (LC3)-I was converted into LC3-II after PRV infection; this transition is considered an important indicator of autophagy. Transmission electron microscopy (TEM) revealed that PRV infection could notably increase the number of autophagosomes in mouse neuro-2a (N2a) cells...
February 13, 2018: Virus Research
Tomokazu Yamaguchi, Takashi Suzuki, Teruki Sato, Akinori Takahashi, Hiroyuki Watanabe, Ayumi Kadowaki, Miyuki Natsui, Hideaki Inagaki, Satoko Arakawa, Shinji Nakaoka, Yukio Koizumi, Shinsuke Seki, Shungo Adachi, Akira Fukao, Toshinobu Fujiwara, Tohru Natsume, Akinori Kimura, Masaaki Komatsu, Shigeomi Shimizu, Hiroshi Ito, Yutaka Suzuki, Josef M Penninger, Tadashi Yamamoto, Yumiko Imai, Keiji Kuba
Shortening and removal of the polyadenylate [poly(A)] tail of mRNA, a process called deadenylation, is a key step in mRNA decay that is mediated through the CCR4-NOT (carbon catabolite repression 4-negative on TATA-less) complex. In our investigation of the regulation of mRNA deadenylation in the heart, we found that this complex was required to prevent cell death. Conditional deletion of the CCR4-NOT complex components Cnot1 or Cnot3 resulted in the formation of autophagic vacuoles and cardiomyocyte death, leading to lethal heart failure accompanied by long QT intervals...
February 6, 2018: Science Signaling
Tie-Feng Song, Li-Wen Huang, Ying Yuan, Hui-Qin Wang, Hong-Peng He, Wen-Jian Ma, Li-Hong Huo, Hao Zhou, Nan Wang, Tong-Cun Zhang
Vascular smooth muscle cells (VSMCs), switching from a differentiated to a proliferative phenotype, contribute to various vascular diseases. However, the role of long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 MALAT1 in the phenotype switching of VSMCs remains unclear. Here, we report that the knockdown of MALAT1 promotes the transformation of smooth muscle cells from a proliferative phenotype to a differentiated phenotype. MALAT1 knockdown inhibited cellular proliferation and migration, leading to significant cell cycle arrest in the G2 phase...
January 12, 2018: Oncotarget
Z-L Wang, Q Deng, T Chong, Z-M Wang
OBJECTIVE: To investigate the effetcs of autophagy on the proliferation of renal carcinoma (RCCs). MATERIALS AND METHODS: Authophagy related protein 7 (Atg7)-overexpressing and knockdown RCC cell lines were established using lentiviral transfection and shRNA interference, respectively. (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) (MTT) was used to determine the Cell growth rate, and western blot was used to determine the expression of protein...
January 2018: European Review for Medical and Pharmacological Sciences
Rui Li, Xin Yi, Xiang Wei, Bo Huo, Xian Guo, Cai Cheng, Ze-Min Fang, Jing Wang, Xin Feng, Ping Zheng, Yun-Shu Su, Jackson Ferdinand Masau, Xue-Hai Zhu, Ding-Sheng Jiang
Enhancer of zeste homolog 2 (EZH2), a methyltransferase that di- and tri-methylates lysine-27 of histone H3, largely functions as a transcriptional repressor, and plays a critical role in various kinds of cancers. Here we report a novel function of EZH2 in regulating autophagic cell death (ACD) of vascular smooth muscle cells (VSMCs) that affect aortic dissection (AD). Inhibition of EZH2 activity by UNC1999 or knockdown EZH2 resulted in VSMC loss, while overexpression of EZH2 facilitated VSMC growth, and these effects of EZH2 on VSMCs were independent of proliferation and apoptosis...
February 7, 2018: Cell Death & Disease
Weiwei Chen, Zili Zhang, Zhen Yao, Ling Wang, Feng Zhang, Jiangjuan Shao, Anping Chen, Shizhong Zheng
Liver fibrosis is a reversible pathophysiological process correlated with intense repair and cicatrization mechanisms, and its end-stage cirrhosis is responsible for high morbidity and mortality worldwide. Interestingly, the use of natural products as a realistic option for the treatment of liver fibrosis has broadly been accepted. Oroxylin A, a safe and natural product, shows a wide range of pharmacological activities such as anti-inflammatory, anti-oxidant, and anti-tumor properties. However, the effects of Oroxylin A on liver fibrosis remain poorly understood...
January 24, 2018: International Immunopharmacology
Toni L Speacht, Andrew R Krause, Jennifer L Steiner, Charles H Lang, Henry J Donahue
Astronauts in space experience a unique environment that causes the concomitant loss of bone and muscle. However, the interaction between these tissues and how osteopenia and sarcopenia affect each other is unclear. We explored this relationship by exaggerating unloading-induced muscle loss using a unilateral casting model in conjunction with hindlimb suspension (HLS). Five-month-old, male C57Bl/6J mice subjected to HLS for 2 weeks displayed a significant decrease in gastrocnemius and quadriceps weight (-9-10%), with a two-fold greater decrease in muscle mass observed in the HLS + casted limb...
February 2, 2018: Bone
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