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https://www.readbyqxmd.com/read/28341893/single-prolonged-stress-induced-changes-in-autophagy-related-proteins-beclin-1-lc3-and-p62-in-the-medial-prefrontal-cortex-of-rats-with-post-traumatic-stress-disorder
#1
Shilei Zheng, Fang Han, Yuxiu Shi, Lili Wen, Dan Han
Autophagy, or type II programmed cell death, plays a crucial role in many nervous system diseases. However, few studies have examined the role of autophagy in post-traumatic stress disorder (PTSD), and the mechanisms underlying PTSD are poorly understood. The objective of this research was to explore the expression of three important autophagy-related proteins, Beclin-1, microtubule-associated protein 1 light chain 3 (LC3), and p62/SQSTM1 (p62), in the medial prefrontal cortex (mPFC) of an animal model of PTSD to identify changes in autophagic activity during PTSD pathogenesis...
March 25, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28341848/role-of-p62-in-the-suppression-of-inflammatory-cytokine-production-by-adiponectin-in-macrophages-involvement-of-autophagy-and-p21-nrf2-axis
#2
Nirmala Tilija Pun, Pil-Hoon Park
Adiponectin possesses potent anti-inflammatory properties. p62, an adaptor protein composed of multi-functional domain, is known to play a role in controlling inflammatory responses. In the present study, we examined the role of p62 in suppressing inflammatory cytokines produced by globular adiponectin (gAcrp) and the potential underlying mechanisms in macrophages. We demonstrated that gAcrp significantly increased p62 expression. Knockdown of p62 abrogated the suppressive effects of gAcrp on LPS-stimulated TNF-α and IL-1β expression and TRAF6/p38 MAPK pathway, indicating that p62 signaling is critical for suppressing inflammatory cytokines production by gAcrp...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28339020/metformin-inhibits-endothelial-progenitor-cell-migration-by-decreasing-matrix-metalloproteinases-mmp-2-and-mmp-9-via-the-ampk-mtor-autophagy-pathway
#3
Wen-Dong Li, Neng-Ping Li, Dan-Dan Song, Jian-Jie Rong, Ai-Min Qian, Xiao-Qiang Li
The aim of the present study was to investigate the effect of metformin on endothelial progenitor cell (EPC) migration and to explore the possible mechanisms. EPCs were treated with metformin, and the migration of EPCs was evaluated by wound healing and Matrigel invasion assays. We also examined the expression levels of of MMP-2 and MMP-9 in EPCs with or without metformin treatment via RT-PCR and western blot analysis, and activities of MMP-2 and MMP-9 in EPCs under different conditions was examined by zymography...
March 21, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28337557/mir-9-enhances-the-sensitivity-of-a549-cells-to-cisplatin-by-inhibiting-autophagy
#4
Yan Zhang, Xia Meng, Cheng Li, Zhoulin Tan, Xinwei Guo, Zhiting Zhang, Tao Xi
OBJECTIVES: To demonstrate that miR-9 inhibits autophagy by down-regulating Beclin1 and thus enhances the sensitivity of A549 cells to cisplatin. RESULTS: MiR-9 inhibited Beclin1 expression by binding to its 3'UTR. The inhibition decreased the cisplatin-induced autophagy in A549 cells, evidenced by the decreased expression of LC3II and GFP-LC3 puncta and the increased expression of P62. Upregulation of miR-9 level enhanced the sensibility of A549 cells to cisplatin and increased the cisplatin-induced apoptosis...
March 23, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28334776/structural-characterization-of-interactions-between-transactivation-domain-1-of-the-p65-subunit-of-nf-%C3%AE%C2%BAb-and-transcription-regulatory-factors
#5
Lauriane Lecoq, Luca Raiola, Philippe R Chabot, Normand Cyr, Geneviève Arseneault, Pascale Legault, James G Omichinski
p65 is a member of the NF-κB family of transcriptional regulatory proteins that functions as the activating component of the p65-p50 heterodimer. Through its acidic transactivation domain (TAD), p65 has the capacity to form interactions with several different transcriptional regulatory proteins, including TFIIB, TFIIH, CREB-binding protein (CBP)/p300 and TAFII31. Like other acidic TADs, the p65 TAD contains two subdomains (p65TA1 and p65TA2) that interact with different regulatory factors depending on the target gene...
February 28, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28333129/protection-against-oxidative-stress-mediated-by-the-nrf2-keap1-axis-is-impaired-in-primary-biliary-cholangitis
#6
Urszula Wasik, Małgorzata Milkiewicz, Agnieszka Kempinska-Podhorodecka, Piotr Milkiewicz
In response to oxidative stress, nuclear factor (erythroid-derived 2)-like2 (Nrf2) induces expression of cytoprotective genes. The Nrf2 pathway is controlled by microRNAs and Kelch-like ECH-associated protein1 (Keap1). Nrf2 is stabilized when Keap1 is degraded through the autophagy pathway in a p62-dependent manner. The inhibition of autophagy causes protein accumulation, and Keap1 is inactivated by binding to p62. We investigated the role of the Nrf2/Keap1 axis in the amelioration of oxidative stress in primary biliary cholangitis (PBC)...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28323964/dysregulated-autophagy-in-hepatocytes-promotes-bisphenol-a-bpa-induced-hepatic-lipid-accumulation-in-male-mice
#7
Shumin Yang, Ting Li, Aipin Zhang, Rufei Gao, Chuan Peng, Lulu Liu, Qingfeng Cheng, Mei Mei, Ying Song, Xiaojiao Xiang, Chaodong Wu, Xiaoqiu Xiao, Qifu Li
Context: Accumulating evidence suggests that bisphenol A (BPA) exposure is associated with nonalcoholic fatty liver disease. Disruption of autophagy causes lipid accumulation in hepatocytes. Whether and how BPA regulates autophagy remains to be explored. Objective: We investigated the effect of BPA on autophagy in hepatocytes and examined the influence of BPA-regulated autophagy on hepatic lipid accumulation. Design: Male CD1 mice were treated with BPA for eight weeks, followed by histological and biochemical evaluation of liver lipids and autophagy...
February 21, 2017: Endocrinology
https://www.readbyqxmd.com/read/28322253/ubiquitylation-of-p62-sequestosome1-activates-its-autophagy-receptor-function-and-controls-selective-autophagy-upon-ubiquitin-stress
#8
Hong Peng, Jiao Yang, Guangyi Li, Qing You, Wen Han, Tianrang Li, Daming Gao, Xiaoduo Xie, Byung-Hoon Lee, Juan Du, Jian Hou, Tao Zhang, Hai Rao, Ying Huang, Qinrun Li, Rong Zeng, Lijian Hui, Hongyan Wang, Qin Xia, Xuemin Zhang, Yongning He, Masaaki Komatsu, Ivan Dikic, Daniel Finley, Ronggui Hu
Alterations in cellular ubiquitin (Ub) homeostasis, known as Ub stress, feature and affect cellular responses in multiple conditions, yet the underlying mechanisms are incompletely understood. Here we report that autophagy receptor p62/sequestosome-1 interacts with E2 Ub conjugating enzymes, UBE2D2 and UBE2D3. Endogenous p62 undergoes E2-dependent ubiquitylation during upregulation of Ub homeostasis, a condition termed as Ub(+) stress, that is intrinsic to Ub overexpression, heat shock or prolonged proteasomal inhibition by bortezomib, a chemotherapeutic drug...
March 21, 2017: Cell Research
https://www.readbyqxmd.com/read/28321785/microrna-34a-suppresses-autophagy-in-alveolar-type-ii-epithelial-cells-in-acute-lung-injury-by-inhibiting-foxo3-expression
#9
Lan Song, Fangliang Zhou, Lijuan Cheng, Mei Hu, Yingchun He, Bo Zhang, Duanfang Liao, Zhaojun Xu
Excessive autophagic activity of alveolar type II epithelial (AT-II) cells is one of the main causes of acute lung injury (ALI); however, the underlying molecular mechanism remains to be determined. The microRNAs (miRNAs) are involved with autophagy in many diseases. The objective of this study was therefore to investigate the relationship between the miRNA expression and the autophagic activity of the AT-II cells in the pathogenesis of ALI and its molecular mechanism. A mouse model of ALI and AT-II cell injury was induced using lipopolysaccharide (LPS) in vivo and in vitro, and the expression of miR-34a and the autophagy-related proteins LC3 II/I and p62 were determined...
March 21, 2017: Inflammation
https://www.readbyqxmd.com/read/28321485/initial-autophagic-protection-switches-to-disruption-of-autophagic-flux-by-lysosomal-instability-during-cadmium-stress-accrual-in-renal-nrk-52e-cells
#10
W-K Lee, S Probst, M P Santoyo-Sánchez, W Al-Hamdani, I Diebels, J-K von Sivers, E Kerek, E J Prenner, F Thévenod
The renal proximal tubule (PT) is the major target of cadmium (Cd(2+)) toxicity where Cd(2+) causes stress and apoptosis. Autophagy is induced by cell stress, e.g., endoplasmic reticulum (ER) stress, and may contribute to cell survival or death. The role of autophagy in Cd(2+)-induced nephrotoxicity remains unsettled due to contradictory results and lack of evidence for autophagic machinery damage by Cd(2+). Cd(2+)-induced autophagy in rat kidney PT cell line NRK-52E and its role in cell death was investigated...
March 20, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28320103/paeoniflorin-ameliorates-ages-induced-mesangial-cell-injury-through-inhibiting-rage-mtor-autophagy-pathway
#11
Juan Chen, Di Zhao, Maomao Zhu, Minghua Zhang, Xuefeng Hou, Wenbo Ding, Shuai Sun, Weiquan Bu, Liang Feng, Shiping Ma, Xiaobin Jia
Glomerular mesangial cell plays a vital role in diabetic nephropathy (DN). Recent research has demonstrated that autophagy involved in the development of DN. Paeoniflorin (PF), a monoterpene glucoside, has been proved to attenuate advanced glycation end products (AGEs)-induced mesangial cell injury. However, the regulatory mechanism of PF on autophagy in mesangial cell remains unclear. The aim of this study was to explore the effect of PF on autophagy in AGEs-induced mesangial cell dysfunction. In this study, the leakage of the lactic dehydrogenase (LDH) into the extracellular medium was measured by LDH kit...
March 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28320092/inhibition-of-pi3k-akt-mtor-signaling-pathway-promotes-autophagy-of-articular-chondrocytes-and-attenuates-inflammatory-response-in-rats-with-osteoarthritis
#12
Jian-Feng Xue, Zhong-Min Shi, Jian Zou, Xiao-Lin Li
OBJECTIVE: This study aims to explore the relationship between PI3K/AKT/mTOR signaling pathway and autophagy of articular chondrocytes in rats with osteoarthritis (OA). METHODS: Rat articular chondrocytes were isolated and cultured, and then induced by protein inhibitors of PI3K/AKT/mTOR signaling pathway. Chondrocytes were assigned into blank group, IL-1β induction group (IL-1β group), PI3K inhibitor+IL-1β induction group (PI3Ki+IL-1β group), AKT inhibitor+IL-1β induction group (AKTi+IL-1β group) and mTOR inhibitor+IL-1β induction group (mTORi+IL-1β group)...
March 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28318044/pathomechanisms-of-anti-cn1a-autoantibodies-in-sporadic-inclusion-body-myositis
#13
Nozomu Tawara, Satoshi Yamashita, Xiao Zhang, Mai Korogi, Ziwei Zhang, Tsukasa Doki, Yoshimasa Matsuo, Shunya Nakane, Yasushi Maeda, Kazuma Sugie, Naoki Suzuki, Masashi Aoki, Yukio Ando
OBJECTIVE: Sporadic inclusion body myositis (sIBM), an intractable progressive muscle disease, frequently occurs in older persons. sIBM pathogenesis may involve protein degradation dysfunction and immune abnormalities. Autoantibodies recognizing cytosolic 5'-nucleotidase 1A (cN1A) were found in plasma and serum from sIBM patients. Whether anti-cN1A autoantibodies play a pathogenic role in sIBM is controversial, however. This study investigated the pathogenic properties of anti-cN1A autoantibodies in sIBM pathogenesis...
March 20, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28316159/-mechanism-of-angiotensin-converting-enzyme-2-overexpression-improving-collagen-synthesis-in-lung
#14
Q J Yang, B B Zheng, N N Sun, M X Pan, Z M Zheng, Y Meng
Objective: To explore the mechanism of angiotensin-converting enzyme 2 (ACE2) overexpression improving collagen synthesis in lung. Methods: Lung fibroblasts of mice over-expressing ACE2 and the wild type (WT) were cultured in vitro and divided into 5 groups: WT-control, WT-AngiotensinⅡ (AngⅡ), ACE2(+ /+) -control, ACE2(+ /+) -AngⅡ and ACE2(+ /+) -AngⅡ+ A779. The protein relative expression levels of ACE2, collagen Ⅰ, nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), autophagy-related protein (Beclin1), ubiquitin-binding protein p62 (P62), microtubule-associated proteins light chain 3-Ⅱ (LC3-Ⅱ) were measured by Western blot and triphosadenine (ATP) level was measured by ATP Assay Kit...
March 14, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28302665/calpain-mobilizes-atg9-bif-1-vesicles-from-golgi-stacks-upon-autophagy-induction-by-thapsigargin
#15
Elena Marcassa, Marzia Raimondi, Tahira Anwar, Eeva-Liisa Eskelinen, Michael P Myers, Gianluca Triolo, Claudio Schneider, Francesca Demarchi
CAPNS1 is essential for stability and function of the ubiquitous calcium dependent proteases micro- and milli-calpain. Upon the inhibition of the endoplasmic reticulum Ca2+ ATPase by 100nM thapsigargin, both micro-calpain and autophagy are activated in human U2OS osteosarcoma cells in a CAPNS1 dependent manner. As reported for other autophagy triggers, thapsigargin treatment induces Golgi fragmentation and fusion of Atg9/Bif-1 containing vesicles with LC3 bodies in control cells. On the opposite, CAPNS1 depletion is coupled to an accumulation of LC3 bodies and Rab5 early endosomes...
March 16, 2017: Biology Open
https://www.readbyqxmd.com/read/28301987/properties-of-epithelial-cells-and-vaginal-secretions-in-pregnant-women-when-lactobacillus-crispatus-or-lactobacillus-iners-dominate-the-vaginal-microbiome
#16
Julie Leizer, Dimitrios Nasioudis, Larry J Forney, G Maria Schneider, Karol Gliniewicz, Allison Boester, Steven S Witkin
OBJECTIVE: Our objective was to determine differences in properties of vaginal epithelial cells and the composition of vaginal secretions when Lactobacillus crispatus or Lactobacillus iners are numerically dominant in the vaginal microenvironment of pregnant women. METHODS: The vaginal microbiomes of 157 first-trimester pregnant women were identified by classifying partial 16S gene sequences amplified from the V1 to V3 region of bacterial ribosomal 16S RNA genes...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28301876/autophagy-inhibitor-chloroquine-increases-sensitivity-to-cisplatin-in-qbc939-cholangiocarcinoma-cells-by-mitochondrial-ros
#17
Xianzhi Qu, Jiyao Sheng, Luyan Shen, Jing Su, Yunjie Xu, Qi Xie, Yao Wu, Xuewen Zhang, Liankun Sun
The tumor cells have some metabolic characteristics of the original tissues, and the metabolism of the tumor cells is closely related to autophagy. However, the mechanism of autophagy and metabolism in chemotherapeutic drug resistance is still poorly understood. In this study, we investigated the role and mechanism of autophagy and glucose metabolism in chemotherapeutic drug resistance by using cholangiocarcinoma QBC939 cells with primary cisplatin resistance and hepatocellular carcinoma HepG2 cells. We found that QBC939 cells with cisplatin resistance had a higher capacity for glucose uptake, consumption, and lactic acid generation, and higher activity of the pentose phosphate pathway compared with HepG2 cells, and the activity of PPP was further increased after cisplatin treatment in QBC939 cells...
2017: PloS One
https://www.readbyqxmd.com/read/28301521/lysosomal-adaptation-how-cells-respond-to-lysosomotropic-compounds
#18
Shuyan Lu, Tae Sung, Nianwei Lin, Robert T Abraham, Bart A Jessen
Lysosomes are acidic organelles essential for degradation and cellular homoeostasis and recently lysosomes have been shown as signaling hub to respond to the intra and extracellular changes (e.g. amino acid availability). Compounds including pharmaceutical drugs that are basic and lipophilic will become sequestered inside lysosomes (lysosomotropic). How cells respond to the lysosomal stress associated with lysosomotropism is not well characterized. Our goal is to assess the lysosomal changes and identify the signaling pathways that involve in the lysosomal changes...
2017: PloS One
https://www.readbyqxmd.com/read/28299821/baby-boomers-in-the-united-states-factors-associated-with-working-longer-and-delaying-retirement
#19
Xiuwen Sue Dong, Xuanwen Wang, Knut Ringen, Rosemary Sokas
OBJECTIVES: This study estimated the self-reported probability of working full-time past age 62 (P62) or age 65 (P65) among four cohorts of Americans born between 1931 and 1959. METHODS: Data from the Health and Retirement Study (HRS) were analyzed. Respondents in four age cohorts were selected for comparison. Multivariable linear regression models were used to assess cohort differences in P62 and P65 while adjusting for covariates. RESULTS: P62 and P65 increased among boomers despite worsened self-rated health compared to the two preceding cohorts, with 37% and 80% increases among mid-boomers in construction trades...
April 2017: American Journal of Industrial Medicine
https://www.readbyqxmd.com/read/28299793/foxo1-ampk-ulk1-regulates-ethanol-induced-autophagy-in-muscle-by-enhanced-atg14-association-with-the-becn1-pik3c3-complex
#20
Ly Q Hong-Brown, C Randell Brown, Maithili Navaratnarajah, Charles H Lang
BACKGROUND: Excessive alcohol (EtOH) consumption causes imbalances in protein metabolism. EtOH impairs protein synthesis in C2C12 myoblasts via a FoxO1-AMPK-TSC2-mTORC1 pathway and also induces degradation. As the underlying regulatory signaling cascades for these processes are currently poorly defined, we tested the hypothesis that alcohol-induced autophagy is mediated via activation of the PIK3C3 complex that is regulated by FoxO1-AMPK. METHODS: C2C12 myoblasts were incubated with EtOH for various periods of time and autophagy pathway-related proteins were assessed by Western blotting and immunoprecipitation...
March 16, 2017: Alcoholism, Clinical and Experimental Research
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