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https://www.readbyqxmd.com/read/29444469/mangiferin-prevents-diabetic-nephropathy-progression-and-protects-podocyte-function-via-autophagy-in-diabetic-rat-glomeruli
#1
Xiaodan Wang, Lihui Gao, Hua Lin, Jingling Song, Jinwen Wang, Yumin Yin, Jianghu Zhao, Xiangwei Xu, Zhenkun Li, Ling Li
Diabetic nephropathy (DN) is one of the most severe microangiopathies of diabetes mellitus and is a leading cause of end stage renal disease. Numerous studies suggest that podocyte injury contributes to progressive proteinuria. Podocytes are highly specialized, terminally differentiated cells that are unable to proliferate, autophagy plays a key role in maintaining the structure and function of podocytes. Autophagy impairment is involved in the pathogenesis of podocyte loss, which leads to massive proteinuria in DN...
February 11, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29433678/wogonin-exacerbates-the-cytotoxic-effect-of-oxaliplatin-by-inducing-nitrosative-stress-and-autophagy-in-human-gastric-cancer-cells
#2
Zhi-Pan Hong, Li-Guo Wang, Hui-Juan Wang, Wei-Feng Ye, Xue-Zhi Wang
BACKGROUND: Gastric cancer remains one of the leading cause of death in the world. Drug combinations are potential approaches to provide more efficient treatments that minimize side effects. PURPOSE: We investigated the pharmacological effects of the combination of wogonin with oxaliplatin on gastric cancer cells in vitro and in vivo. METHODS AND RESULTS: In the present study, we found that wogonin enhanced the cytotoxicity of oxaliplatin; the drug combination resulted in strong synergistic inhibition of the cell viability in BGC-823 cells and in a zebrafish xenograft model...
January 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29425491/tbk1-at-the-crossroads-of-inflammation-and-energy-homeostasis-in-adipose-tissue
#3
Peng Zhao, Kai In Wong, Xiaoli Sun, Shannon M Reilly, Maeran Uhm, Zhongji Liao, Yuliya Skorobogatko, Alan R Saltiel
The noncanonical IKK family member TANK-binding kinase 1 (TBK1) is activated by pro-inflammatory cytokines, but its role in controlling metabolism remains unclear. Here, we report that the kinase uniquely controls energy metabolism. Tbk1 expression is increased in adipocytes of HFD-fed mice. Adipocyte-specific TBK1 knockout (ATKO) attenuates HFD-induced obesity by increasing energy expenditure; further studies show that TBK1 directly inhibits AMPK to repress respiration and increase energy storage. Conversely, activation of AMPK under catabolic conditions can increase TBK1 activity through phosphorylation, mediated by AMPK's downstream target ULK1...
February 8, 2018: Cell
https://www.readbyqxmd.com/read/29391491/mir-26a-5p-regulates-cardiac-fibroblasts-collagen-expression-by-targeting-ulk1
#4
Liling Zheng, Sihuang Lin, Chengyu Lv
MiRNA is a class of small non-coding RNA which has an important effect on posttranscriptional gene regulation. It can regulate the expression of the target gene at the mRNA level and further influence the protein level of the target gene. We found that ULK1 may be the target gene of miR-26a-5p, and ULK1 (unc-51 like autophagy activating kinase 1) is a key component in autophagy pathway. In this study, we overexpressed miR-26a-5p by transfecting miR-26a-5p mimic into cells and simultaneously inhibited miR-26a-5p by transfecting miR-26a-5p inhibitor into cells...
February 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29384220/compound-c-induces-protective-autophagy-in-human-cholangiocarcinoma-cells-via-akt-mtor-independent-pathway
#5
Xiaofang Zhao, Guosong Luo, Ying Cheng, Wenjing Yu, Run Chen, Bin Xiao, Yuancai Xiang, Chunhong Feng, Wenguang Fu, Chunyan Duan, Fuli Yao, Xianming Xia, Qinghua Tao, Mei Wei, Rongyang Dai
Compound C, a well-known inhibitor of AMP-activated protein kinase (AMPK), has been reported to exert antitumor activities in some types of cells. Whether compound C can exert antitumor effects in human cholangiocarcinoma (CCA) remains unknown. Here, we demonstrated that compound C is a potent inducer of cell death and autophagy in human CCA cells. Autophagy inhibitors increased the cytotoxicity of compound C towards human CCA cells, as confirmed by increased LDH release and PARP cleavage. It is notable that compound C treatment increased phosphorylated Akt, sustained high levels of phosphorylated p70S6K and decreased mTOR regulated p-ULK1 (ser757)...
January 31, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29360511/responders-and-non-responders-to-influenza-vaccination-a-dna-methylation-approach-on-blood-cells
#6
Noémie Gensous, Claudio Franceschi, Bonnie B Blomberg, Chiara Pirazzini, Francesco Ravaioli, Davide Gentilini, Anna Maria Di Blasio, Paolo Garagnani, Daniela Frasca, Maria Giulia Bacalini
Several evidences indicate that aging negatively affects the effectiveness of influenza vaccination. Although it is well established that immunosenescence has an important role in vaccination response, the molecular pathways underlying this process are largely unknown. Given the importance of epigenetic remodeling in aging, here we analyzed the relationship between responsiveness to influenza vaccination and DNA methylation profiles in healthy subjects of different ages. Peripheral blood mononuclear cells were collected from 44 subjects (age range: 19-90 years old) immediately before influenza vaccination...
January 19, 2018: Experimental Gerontology
https://www.readbyqxmd.com/read/29348830/inactivation-deficiency-of-dhodh-induces-cell-cycle-arrest-and-programed-cell-death-in-melanoma
#7
Lichao Liu, Zhen Dong, Qian Lei, Jie Yang, Huanrong Hu, Qian Li, Yacong Ji, Leiyang Guo, Yanli Zhang, Yaling Liu, Hongjuan Cui
Malignant melanoma (MM) is one of the most malignant tumors and has a very poor prognosis. However, there are no effective drugs to treat this disease. As a kind of iron flavin dependent enzyme, dihydroorotate dehydrogenase (DHODH, EC 1.3.3.1) is the fourth and a key enzyme in the de novo biosynthesis of pyrimidines. Herein, we found that DHODH inactivation/deficiency inhibited melanoma cell proliferation, induced cell cycle arrest at S phase and lead to autophagy in human melanoma cells. Meanwhile, leflunomide treatment induced cell apoptosis and deficiency of DHODH sensitized cells to drug-induced apoptosis in BCL-2 deficient melanoma cells, while not in BCL-2 abundant melanoma cells...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348566/phosphorylation-of-ulk1-by-ampk-is-essential-for-mouse-embryonic-stem-cell-self-renewal-and-pluripotency
#8
Jiaqi Gong, Haifeng Gu, Lin Zhao, Liang Wang, Pinglei Liu, Fuping Wang, Haoyu Xu, Tongbiao Zhao
Autophagy is a catabolic process to degrade both damaged organelles and aggregated proteins in somatic cells. We have recently identified that autophagy is an executor for mitochondrial homeostasis in embryonic stem cell (ESC), and thus contribute to stemness regulation. However, the regulatory and functional mechanisms of autophagy in ESC are still largely unknown. Here we have shown that activation of ULK1 by AMPK is essential for ESC self-renewal and pluripotency. Dysfunction of Ulk1 decreases the autophagic flux in ESC, leading to compromised self-renewal and pluripotency...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348263/phosphoinositide-3-kinase-gamma-inhibition-protects-from-anthracycline-cardiotoxicity-and-reduces-tumor-growth
#9
Mingchuan Li, Valentina Sala, Maria Chiara De Santis, James Cimino, Paola Cappello, Nicola Pianca, Anna Di Bona, Jean Piero Margaria, Miriam Martini, Edoardo Lazzarini, Flora Pirozzi, Luca Rossi, Irene Franco, Julia Bornbaum, Jacqueline Heger, Susanne Rohrbach, Alessia Perino, Carlo G Tocchetti, Braulio H F Lima, Mauro M Teixeira, Paolo E Porporato, Rainer Schulz, Annalisa Angelini, Marco Sandri, Pietro Ameri, Sebastiano Sciarretta, Roberto César P Lima-Júnior, Marco Mongillo, Tania Zaglia, Fulvio Morello, Francesco Novelli, Emilio Hirsch, Alessandra Ghigo
Background -Anthracyclines, such as doxorubicin (DOX), are potent anti-cancer agents for the treatment of solid tumors and hematological malignancies. However, their clinical use is hampered by cardiotoxicity. This study sought to investigate the role of PI3Kγ in DOX-induced cardiotoxicity and the potential cardio-protective and anti-cancer effects of PI3Kγ inhibition. Methods -Mice expressing a kinase-inactive PI3Kγ or receiving PI3Kγ selective inhibitors were subjected to chronic DOX treatment. Cardiac function was analyzed by echocardiography and DOX-mediated signaling was assessed in whole hearts or in isolated cardiomyocytes...
January 18, 2018: Circulation
https://www.readbyqxmd.com/read/29344647/autophagy-regulates-the-degeneration-of-the-auditory-cortex-through-the-ampk-mtor-ulk1-signaling-pathway
#10
Jie Yuan, Xueyan Zhao, Yujuan Hu, Haiying Sun, Guoqing Gong, Xiang Huang, Xubo Chen, Mingyu Xia, Chen Sun, Qilin Huang, Yu Sun, Wen Kong, Weijia Kong
Presbycusis is the most common sensory impairment associated with aging; however, the underlying molecular mechanism remains unclear. Autophagy has been demonstrated to serve a key role in diverse diseases; however, no studies have examined its function in central presbycusis. The aim of the present study was to investigate the changes of autophagy in the physiological processes of the auditory cortex and its role in the degeneration of the auditory cortex, as well as the related mechanisms using naturally aging rats and a D‑galactose (D‑gal)‑induced mimetic rat model of aging...
January 17, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29344024/elevated-phosphate-levels-trigger-autophagy-mediated-cellular-apoptosis-in-h9c2-cardiomyoblasts
#11
Yao-Lung Liu, Kuan-Ho Lin, Shanmugam Tamilselvi, Wei-Kung Chen, Chia-Yao Shen, Ray-Jade Chen, Cecilia Hsuan Day, Hsi-Chin Wu, Vijaya Padma Viswanadha, Chih-Yang Huang
BACKGROUND/AIM: In chronic kidney disease (CKD), kidneys fail to maintain phosphorus homeostasis in serum. Elevated phosphorus levels in serum have been associated with cardiovascular diseases in CKD patients and in normal individuals. In this study, we evaluated the level of autophagy- and apoptosis-related markers under different concentrations of hyperphosphate in myocardial cells. METHODS: Modulation inflicted on the levels of various survival-, autophagy-, and apoptosis-related markers were determined by Western blotting analysis using total protein extract...
December 2017: Cardiorenal Medicine
https://www.readbyqxmd.com/read/29333953/the-irreversible-erbb1-2-4-inhibitor-neratinib-interacts-with-the-bcl-2-inhibitor-venetoclax-to-kill-mammary-cancer-cells
#12
Laurence Booth, Jane L Roberts, Francesca Avogadri-Connors, Richard E CutlerJr, Alshad S Lalani, Andrew Poklepovic, Paul Dent
The irreversible ERBB1/2/4 inhibitor, neratinib, down-regulates the expression of ERBB1/2/4 as well as the levels of MCL-1 and BCL-XL. Venetoclax (ABT199) is a BCL-2 inhibitor. At physiologic concentrations neratinib interacted in a synergistic fashion with venetoclax to kill HER2+ and TNBC mammary carcinoma cells. This was associated with the drug-combination: reducing the expression and phosphorylation of ERBB1/2/3; in an eIF2α-dependent fashion reducing the expression of MCL-1 and BCL-XL and increasing the expression of Beclin1 and ATG5; and increasing the activity of the ATM-AMPKα-ULK1 S317 pathway which was causal in the formation of toxic autophagosomes...
January 15, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29330382/sesn2-facilitates-mitophagy-by-helping-parkin-translocation-through-ulk1-mediated-beclin1-phosphorylation
#13
Ashish Kumar, Chandrima Shaha
Mitophagy, the selective degradation of mitochondria by autophagy, is crucial for the maintenance of healthy mitochondrial pool in cells. The critical event in mitophagy is the translocation of cytosolic Parkin, a ubiquitin ligase, to the surface of defective mitochondria. This study elucidates a novel role of SESN2/Sestrin2, a stress inducible protein, in mitochondrial translocation of PARK2/Parkin during mitophagy. The data demonstrates that SESN2 downregulation inhibits BECN1/Beclin1 and Parkin interaction, thereby preventing optimum mitochondrial accumulation of Parkin...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29321503/il-34-and-csf-1-display-an-equivalent-macrophage-differentiation-ability-but-a-different-polarization-potential
#14
Sonia Boulakirba, Anja Pfeifer, Rana Mhaidly, Sandrine Obba, Michael Goulard, Thomas Schmitt, Paul Chaintreuil, Anne Calleja, Nathan Furstoss, François Orange, Sandra Lacas-Gervais, Laurent Boyer, Sandrine Marchetti, Els Verhoeyen, Frederic Luciano, Guillaume Robert, Patrick Auberger, Arnaud Jacquel
CSF-1 and IL-34 share the CSF-1 receptor and no differences have been reported in the signaling pathways triggered by both ligands in human monocytes. IL-34 promotes the differentiation and survival of monocytes, macrophages and osteoclasts, as CSF-1 does. However, IL-34 binds other receptors, suggesting that differences exist in the effect of both cytokines. In the present study, we compared the differentiation and polarization abilities of human primary monocytes in response to CSF-1 or IL-34. CSF-1R engagement by one or the other ligands leads to AKT and caspase activation and autophagy induction through expression and activation of AMPK and ULK1...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29321306/digitoxin-suppresses-human-cytomegalovirus-replication-via-na-k-atpase-%C3%AE-1-subunit-dependent-ampk-and-autophagy-activation
#15
Rupkatha Mukhopadhyay, Rajkumar Venkatadri, Jenny Katsnelson, Ravit Arav-Boger
Host-directed therapeutics for human cytomegalovirus (HCMV) requires elucidation of cellular mechanisms that inhibit HCMV. We report on a novel pathway used by cardiac glycosides to inhibit HCMV replication: induction of AMPK activity and autophagy flux through the Na+, K+/ATPase α1 subunit. Our data illustrate an intricate balance between autophagy regulators AMPK, mTOR and ULK1 during infection and treatment with the cardiac glycoside, digitoxin. Both infection and digitoxin induced AMPK phosphorylation, but ULK1 was differentially phosphorylated at unique sites leading to opposing effects on autophagy...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29315230/maternal-high-fructose-intake-increases-the-vulnerability-to-post-weaning-high-fat-diet-induced-programmed-hypertension-in-male-offspring
#16
You-Lin Tain, Wei-Chia Lee, Kay L H Wu, Steve Leu, Julie Y H Chan
Widespread consumption of high-fructose and high-fat diets relates to the global epidemic of hypertension. Hypertension may originate from early life by a combination of prenatal and postnatal nutritional insults. We examined whether maternal high-fructose diet increases vulnerability to post-weaning high-fructose or high-fat diets induced hypertension in adult offspring and determined the underlying mechanisms. Pregnant Sprague-Dawley rats received regular chow (ND) or chow supplemented with 60% fructose (HFR) during the entire pregnancy and lactation periods...
January 9, 2018: Nutrients
https://www.readbyqxmd.com/read/29313410/ulk1-phosphorylates-ser30-of-becn1-in-association-with-atg14-to-stimulate-autophagy-induction
#17
Ji-Man Park, Minchul Seo, Chang Hwa Jung, Douglas Grunwald, Matthew Stone, Neil Michael Otto, Erik Toso, Yeseul Ahn, Michael Kyba, Timothy J Griffin, LeeAnn Higgins, Do-Hyung Kim
ULK1 (unc51-like autophagy activating kinase 1) is a serine/threonine kinase that plays a key role in regulating macroautophagy/autophagy induction in response to amino acid starvation. Despite the recent progress in understanding ULK1 functions, the molecular mechanism by which ULK1 regulates the induction of autophagy remains elusive. In this study, we determined that ULK1 phosphorylates Ser30 of BECN1 (beclin 1) in association with ATG14 (autophagy related 14) but not with UVRAG (UV radiation resistance associated)...
January 9, 2018: Autophagy
https://www.readbyqxmd.com/read/29304491/influences-of-different-dietary-energy-level-on-sheep-testicular-development-associated-with-ampk-ulk1-autophagy-pathway
#18
Jing Pang, Fengzhe Li, Xu Feng, Hua Yang, Le Han, Yixuan Fan, Haitao Nie, Zhen Wang, Feng Wang, Yanli Zhang
Energy balance is an important feature for spermatozoa production in the testis. The 5'-AMP-activated protein kinase (AMPK) is a sensor of cell energy, has been implicated as a mediator between gonadal function and energy balance. Herein, we intended to determine the physiological effects of AMPK on testicular development in feed energy restricted and compensated pre-pubertal rams. Lambs had restricted feeding for 2 months and then provided compensatory feeding for another 3 months. Feed levels were 100%(control), 15% and 30% of energy restriction (ER) diets, respectively...
December 14, 2017: Theriogenology
https://www.readbyqxmd.com/read/29278652/parp1-induces-cardiac-fibrosis-by-mediating-mtor-activity
#19
Shuya Sun, Yuehuai Hu, Qiyao Zheng, Zhen Guo, Duanping Sun, Shaorui Chen, Yiqiang Zhang, Peiqing Liu, Jing Lu, Jianmin Jiang
Cardiac fibrosis is involved in nearly all forms of heart diseases, and is characterized by excessive deposition of extracellular matrix (ECM) proteins by cardiac fibroblasts (CFs). We and others have reported the possibility of poly(ADP-ribose) polymerase 1 (PARP1), the founding subtype of the PARPs enzyme family, as a novel therapeutic target of heart diseases. The cardiac fibrotic induction of mTOR (mammalian target of rapamycin) is mainly due to collagen expression, Smad3 and p53/JNK-mediated apoptosis...
December 26, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29277967/induction-of-autophagy-and-autophagy-dependent-apoptosis-in-diffuse-large-b-cell-lymphoma-by-a-new-antimalarial-artemisinin-derivative-sm1044
#20
Chunyan Cheng, Tao Wang, Zhiqun Song, Lijun Peng, Mengqing Gao, Olivier Hermine, Sophie Rousseaux, Saadi Khochbin, Jian-Qing Mi, Jin Wang
Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin's lymphoma. R-CHOP is currently the standard therapy for DLBCL, but the prognosis of refractory or recurrent patients remains poor. In this study, we synthesized a new water-soluble antimalarial drug artemisinin derivative, SM1044. The treatment of DLBCL cell lines with SM1044 induces autophagy-dependent apoptosis, which is directed by an accelerated degradation of the antiapoptosis protein Survivin, via its acetylation-dependent interaction with the autophagy-related protein LC3-II...
December 26, 2017: Cancer Medicine
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