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https://www.readbyqxmd.com/read/29164996/cptp-a-sphingolipid-transfer-protein-that-regulates-autophagy-and-inflammasome-activation
#1
Shrawan Kumar Mishra, Yong-Guang Gao, Yibin Deng, Charles E Chalfant, Edward H Hinchcliffe, Rhoderick E Brown
The macroautophagy/autophagy and inflammasome pathways are linked through their roles in innate immunity and chronic inflammatory disease. Ceramide-1-phosphate (C1P) is a bioactive sphingolipid that regulates pro-inflammatory eicosanoid production. Whether C1P also regulates autophagy and inflammasome assembly/activation is not known. Here we show that CPTP (a protein that traffics C1P from its site of phosphorylation in the trans-Golgi to target membranes) regulates both autophagy and inflammasome activation...
November 22, 2017: Autophagy
https://www.readbyqxmd.com/read/29154199/ultraviolet-b-radiation-down-regulates-ulk1-and-atg7-expression-and-impairs-the-autophagy-response-in-human-keratinocytes
#2
Xu Chen, Li Li, Song Xu, Wenbo Bu, Kun Chen, Min Li, Heng Gu
Autophagy is a self-digestive pathway that helps to maintain cellular homeostasis, and many autophagy-related gene (ATG)s involved the regulation of the autophagy process. Ultraviolet light is a common stressor of skin, but it is unclear how autophagy is regulated after ultraviolet exposure in epidermal keratinocytes. Here, we found that the mRNAs of some key ATG genes such as ULK1, ATG5 and ATG7 exhibited significantly lower levels in the skin tissues of the face and chest with solar ultraviolet exposure, compared with perineal skin...
September 4, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/29146131/dysregulation-of-autophagy-in-melanocytes-contributes-to-hypopigmented-macules-in-tuberous-sclerosis-complex
#3
Fei Yang, Lingli Yang, Mari Wataya-Kaneda, Junya Hasegawa, Tamotsu Yoshimori, Atsushi Tanemura, Daisuke Tsuruta, Ichiro Katayama
BACKGROUND: Tuberous sclerosis complex (TSC) gene mutations lead to constitutive activation of the mammalian target of rapamycin (mTOR) pathway, resulting in a broad range of symptoms. Hypopigmented macules are the earliest sign. Although we have already confirmed that topical rapamycin treatment (an mTOR inhibitor) protects patients with TSC against macular hypopigmentation, the pathogenesis of such lesions remains poorly understood. OBJECTIVE: Recently emerging evidence supports a role for autophagy in skin pigmentation...
November 11, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/29142990/the-chemical-chaperone-pba-reduces-er-stress-and-autophagy-and-increases-collagen-iv-%C3%AE-5-expression-in-cultured-fibroblasts-from-men-with-x-linked-alport-syndrome-and-missense-mutations
#4
Dongmao Wang, Mardhiah Mohammad, Yanyan Wang, Rachel Tan, Lydia S Murray, Sharon Ricardo, Hayat Dagher, Tom van Agtmael, Judy Savige
Introduction: X-linked Alport syndrome (OMIM 301050) is caused by COL4A5 missense variants in 40% of families. This study examined the effects of chemical chaperone treatment (sodium 4-phenylbutyrate) on fibroblast cell lines derived from men with missense mutations. Methods: Dermal fibroblast cultures were established from 2 affected men and 3 normals. Proliferation rates were examined, the collagen IV α5 chain localized with immunostaining, and levels of the intra- and extracellular chains quantitated with an in-house enzyme-linked immunosorbent assay...
July 2017: KI Reports
https://www.readbyqxmd.com/read/29138806/effect-of-bis-hydroxymethyl-alkanoate-curcuminoid-derivative-mth-3-on-cell-cycle-arrest-apoptotic-and-autophagic-pathway-in-triple-negative-breast-adenocarcinoma-mda-mb-231-cells-an-in-vitro-study
#5
Ling-Chu Chang, Min-Tsang Hsieh, Jai-Sing Yang, Chi-Cheng Lu, Fuu-Jen Tsai, Je-Wei Tsao, Yu-Jen Chiu, Sheng-Chu Kuo, Kuo-Hsiung Lee
Curcumin has been shown to exert potential antitumor activity in vitro and in vivo involved in multiple signaling pathways. However, the application of curcumin is still limited because of its poor hydrophilicity and low bio-availability. In the present study, we investigated the therapeutic effects of a novel and water soluble bis(hydroxymethyl) alkanoate curcuminoid derivative, MTH-3, on human breast adenocarcinoma MDA-MB-231 cells. This study investigated the effect of MTH-3 on cell viability, cell cycle and induction of autophagy and apoptosis in MDA-MB-231 cells...
November 14, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29137257/kaempferol-induces-hepatocellular-carcinoma-cell-death-via-endoplasmic-reticulum-stress-chop-autophagy-signaling-pathway
#6
Haiqing Guo, Wei Lin, Xiangying Zhang, Xiaohui Zhang, Zhongjie Hu, Liying Li, Zhongping Duan, Jing Zhang, Feng Ren
Kaempferol is a flavonoid compound that has gained widespread attention due to its antitumor functions. However, the underlying mechanisms are still not clear. The present study investigated the effect of kaempferol on hepatocellular carcinoma and its underlying mechanisms. Kaempferol induced autophagy in a concentration- and time-dependent manner in HepG2 or Huh7 cells, which was evidenced by the significant increase of autophagy-related genes. Inhibition of autophagy pathway, through 3-methyladenine or Atg7 siRNA, strongly diminished kaempferol-induced apoptosis...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136784/the-alternation-of-autophagy-apoptosis-in-cd4-cd25-foxp3-tregs-on-the-developmental-stages-of-atherosclerosis
#7
Yuling Tian, Xiao Liang, Yue Wu
Naturally regulatory T cells (Tregs) play a critical role in the regulation of T cell-mediated immune responses in atherosclerosis. However, the regulatory mechanism underlying Tregs upon long-term development of atherosclerosis remains unknown. Therefore, in this study, atherosclerotic model was induced in ApoE-/- mice by feeding fat-diet for 10 weeks. Quantification of atherosclerotic lesions was done by calculating the lesion size in the aortic sinus every 2 weeks. The lipid levels and inflammatory mediators were detected in serum sample...
November 8, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29130967/endoplasmic-reticulum-stress-promotes-autophagy-and-apoptosis-and-reduces-chemotherapy-resistance-in-mutant-p53-lung-cancer-cells
#8
Ping-Ping Gan, Yang-Ying Zhou, Mei-Zuo Zhong, Yun Peng, Li Li, Jian-Huang Li
BACKGROUND/AIMS: Lung cancer (LC) continues to be one of the most prevalent cancers around the world. During this study we aimed to investigate the involvement of endoplasmic reticulum stress (ERS) in autophagy, apoptosis, and chemotherapy resistance of mutant p53 LC cells. METHODS: Immunohistochemistry was employed to help determine the p53 mutation status of cancer cells from 92 primary LC patients, who were subsequently assigned to either the mutant p53 (n = 39) or wild-type p53 group (n = 53)...
November 6, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29130361/mta1-is-a-novel-regulator-of-autophagy-that-induces-tamoxifen-resistance-in-breast-cancer-cells
#9
Min-Ho Lee, Dahae Koh, Hyelin Na, Na-Lee Ka, Seungsu Kim, Hyeon-Ji Kim, Sungyoul Hong, Young Kee Shin, Je Kyung Seong, Mi-Ock Lee
Tamoxifen is commonly used to treat patients with ESR/ER-positive breast cancer, but its therapeutic benefit is limited by the development of resistance. Recently, alterations in macroautophagy/autophagy function were demonstrated to be a potential mechanism for tamoxifen resistance. Although MTA1 (metastasis-associated 1) has been implicated in breast tumorigenesis and metastasis, its role in endocrine resistance has not been studied. Here, we report that the level of MTA1 expression was upregulated in the tamoxifen resistant breast cancer cell lines MCF7/TAMR and T47D/TR, and knockdown of MTA1 sensitized the cells to 4-hydroxytamoxifen (4OHT)...
November 13, 2017: Autophagy
https://www.readbyqxmd.com/read/29130102/knockdown-of-lncrna-xist-enhances-the-chemosensitivity-of-nsclc-cells-via-suppression-of-autophagy
#10
Wei Sun, Yukun Zu, Xiangning Fu, Yu Deng
Drug resistance is the major factor contributing to the failure of chemotherapy in non-small cell lung cancer (NSCLC) patients. Emerging evidence suggests that autophagy plays a vital role in the chemoresistance of many types of tumors. However, the exact mechanism underlying the chemoresistance of NSCLC is still elusive, and it is unclear whether lncRNA-XIST is involved in autophagy and chemoresistance of NSCLC. In the present study, we demonstrated that lncRNA-XIST was overexpressed in NSCLC tumor samples, and knockdown of lncRNA-XIST significantly decreased autophagy by regulation of ATG7 as determined by qPCR and by western blotting...
December 2017: Oncology Reports
https://www.readbyqxmd.com/read/29125039/astrocyte-autophagy-flux-protects-neurons-against-oxygen-glucose-deprivation-and-ischemic-reperfusion-injury
#11
Xue Liu, Fengfeng Tian, Shiquan Wang, Feng Wang, Lize Xiong
The role of autophagy varies with the type of acute brain injury. In general, autophagy mediates a clear neuroprotective effect in intoxication caused by various psychoactive agents, subarachnoid hemorrhage and spinal cord injury. In contrast, autophagic cell death has also been reported to actively contribute to neuronal loss in neonatal hypoxic ischemic encephalopathy. However, it still remains to be determined whether autophagy pays a cytoprotective or a cytotoxic role in stroke. Previous studies focused primarily on the role of neurons rather than the role of astrocytes in brain injury...
November 10, 2017: Rejuvenation Research
https://www.readbyqxmd.com/read/29123153/a-genome-wide-association-study-links-small-vessel-ischemic-stroke-to-autophagy
#12
Tsong-Hai Lee, Tai-Ming Ko, Chien-Hsiun Chen, Yeu-Jhy Chang, Liang-Suei Lu, Chien-Hung Chang, Kuo-Lun Huang, Ting-Yu Chang, Jiann-Der Lee, Ku-Chou Chang, Jen-Tsung Yang, Ming-Shien Wen, Chao-Yung Wang, Ying-Ting Chen, Tsai-Chuan Chen, Shu-Yu Chou, Ming-Ta Michael Lee, Yuan-Tsong Chen, Jer-Yuarn Wu
Genome-wide association studies (GWAS) can serve as strong evidence in correlating biological pathways with human diseases. Although ischemic stroke has been found to be associated with many biological pathways, the genetic mechanism of ischemic stroke is still unclear. Here, we performed GWAS for a major subtype of stroke-small-vessel occlusion (SVO)-to identify potential genetic factors contributing to ischemic stroke. GWAS were conducted on 342 individuals with SVO stroke and 1,731 controls from a Han Chinese population residing in Taiwan...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29122566/mutations-of-candidate-tumor-suppressor-genes-at-chromosome-3p-in-intrahepatic-cholangiocarcinoma
#13
Huey-Ling You, Wan-Ting Huang, Ting-Ting Liu, Shao-Wen Weng, Hock-Liew Eng
The genetic status of candidate tumor suppressor genes (TSGs) at chromosome 3p has not yet been elucidated in intrahepatic cholangiocarcinoma (iCCA). Herein, we retrospectively investigated 32 fresh iCCA case samples from a single medical institution to clarify mutations of 11 TSGs by next-generation sequencing. Validation of the mutations was performed on the MassARRAY platform or by high-resolution melting curve analysis. We then integrated the gene mutations into copy number alterations at chromosome 3p that had been generated in a previous study using the same fresh iCCA samples, and correlated the integration results with the clinicopathologic features...
November 7, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29115429/resveratrol-mediated-apoptosis-in-renal-cell-carcinoma-via-the-p53-amp%C3%A2-activated-protein-kinase-mammalian-target-of-rapamycin-autophagy-signaling-pathway
#14
Qingjun Liu, Qiang Fang, Shiqi Ji, Zhixing Han, Wenlong Cheng, Haijian Zhang
Resveratrol, known as phytoalexin, is a natural compound. Clinical studies have revealed that resveratrol has a variety of effects including anti‑inflammatory, antivirus and tumor suppressor activities. It has been reported that it may serve an important role in renal cell carcinoma (RCC) however, the molecular mechanism underlying resveratrol‑induced apoptosis in RCC is still unclear. The aim of the present study was to determine whether resveratrol could suppress RCC progression. Analysis of apoptosis demonstrated that resveratrol may act as a RCC suppressor in a dose‑ and time‑dependent manner...
October 25, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29107181/antimony-trichloride-induces-a-loss-of-cell-viability-via-reactive-oxygen-species-dependent-autophagy-in-a549-cells
#15
Xinyuan Zhao, Fengjun Xing, Yewen Cong, Yin Zhuang, Muxi Han, Zhiqiang Wu, Shali Yu, Haiyan Wei, Xiaoke Wang, Gang Chen
Antimony (Sb) is one of the most prevalent heavy metals and frequently leads to biological toxicity. Although autophagy is believed to be involved in metal-associated cytotoxicity, there is no evidence of its involvement following exposure. Moreover, the underlying mechanism of autophagy remains unclear. In this study, treatment with antimony trichloride caused autophagy in a dose- and time-dependent manner in A549 cells but did not affect the level of Atg5 or Atg7 mRNA expression. Furthermore, Sb enhanced autophagic flux while upregulating p62 gene and protein levels...
October 26, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29099309/the-autophagy-inducing-kinases-ulk1-and-ulk2-regulate-axon-guidance-in-the-developing-mouse-forebrain-via-a-noncanonical-pathway
#16
Bo Wang, Rekha Iyengar, Xiujie Li-Harms, Joung Hyuck Joo, Christopher Wright, Alfonso Lavado, Linda Horner, Mao Yang, Jun-Lin Guan, Sharon Frase, Douglas R Green, Xinwei Cao, Mondira Kundu
Mammalian ULK1 (unc-51 like kinase 1) and ULK2, Caenorhabditis elegans UNC-51, and Drosophila melanogaster Atg1 are serine/threonine kinases that regulate flux through the autophagy pathway in response to various types of cellular stress. C. elegans UNC-51 and D. melanogaster Atg1 also promote axonal growth and defasciculation; disruption of these genes results in defective axon guidance in invertebrates. Although disrupting ULK1/2 function impairs normal neurite outgrowth in vitro, the role of ULK1 and ULK2 in the developing brain remains poorly characterized...
November 3, 2017: Autophagy
https://www.readbyqxmd.com/read/29091873/autophagy-participates-in-isoliquiritigenin-induced-melanin-degradation-in-human-epidermal-keratinocytes-through-pi3k-akt-mtor-signaling
#17
Zhibo Yang, Biyun Zeng, Yi Pan, Pan Huang, Chang Wang
Melanin is the pigment responsible for the color of human skin and hair. Melanin serves as a double-edge sword which can exert both protective and spot-causing effects on skin. Although melanin has an important role in protecting the skin against UV damage, an excessive or uneven melanin production can lead to the formation of freckles and age spots. Isoliquiritigenin (ISL) has been reported to inhibit melanin synthesis; however, its role in melanin degradation remains unclear. In the present study, we evaluated the detailed function of ISL in melanin degradation in human epidermal keratinocytes...
October 26, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29089548/hla-dmb-restricts-human-t-cell-leukemia-virus-type-1-htlv-1-protein-expression-via-regulation-of-atg7-acetylation
#18
Jie Wang, Di Song, Yanzi Liu, Guangjian Lu, Shuai Yang, Lu Liu, Zhitao Gao, Lingling Ma, Zhixiang Guo, Chenguang Zhang, Hui Wang, Bo Yang
The roles of autophagy in viral infection are complicated. While autophagy has been shown to function in host antiviral defense by eliminating intracellular viruses and regulating adaptive immunity, several viruses have evolved molecular mechanisms to get benefits from it. The deltaretrovirus human T-cell leukemia virus type-1 (HTLV-1) has been reported to profit its replication from enhancing autophagosome accumulation. Here, we reported that HLA-DMB (generally referred to here as DMB), the beta chain of the non-classical MHC-II protein HLA-DM, had strong expression in HTLV-1-transformed T-cell lines and could be induced in Hela, PMA-differentiated THP1 (PMA-THP1) or primary human monocytes by HTLV-1 infection...
October 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29078374/taurine-ameliorates-particulate-matter-induced-emphysema-by-switching-on-mitochondrial-nadh-dehydrogenase-genes
#19
Xiaobo Li, Hongbao Yang, Hao Sun, Runze Lu, Chengcheng Zhang, Na Gao, Qingtao Meng, Shenshen Wu, Susanna Wang, Michael Aschner, Jiong Wu, Boping Tang, Aihua Gu, Steve A Kay, Rui Chen
Chronic obstructive pulmonary disease (COPD) has been linked to particulate matter (PM) exposure. Using transcriptomic analysis, we demonstrate that diesel exhaust particles, one of the major sources of particulate emission, down-regulated genes located in mitochondrial complexes I and V and induced experimental COPD in a mouse model. 1-Nitropyrene was identified as a major toxic component of PM-induced COPD. In the panel study, COPD patients were found to be more susceptible to PM than individuals with normal lung function due to an increased inflammatory response...
November 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29068103/desipramine-induced-lysosomal-vacuolization-is-independent-of-autophagy
#20
Hirofumi Sawai
Desipramine, a commonly used antidepressant drug, induced cytosolic vacuolization in L929 cells. The level of LC3-II was elevated and that of p62 was reduced in desipramine-treated L929 cells, indicating the induction of autophagy by desipramine. Surprisingly, massive vacuolization was observed in desipramine-treated L929 cells in the presence of LY294002, an inhibitor of autophagy. On the other hand, bafilomycin A1, an inhibitor of vacuolar type H(+) ATPase, almost completely inhibited vacuolization in desipramine- or desipramine/LY294002-treated L929 cells...
October 25, 2017: Cell Biology International
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