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Yang Su, Jingxiao Lu, Xianguo Chen, Chaozhao Liang, Pengcheng Luo, Cong Qin, Jie Zhang
Chronic prostatitis (CP) is a clinically common disease with high morbidity. It affects the patients' quality of life (QoL) as well as physical and mental health seriously due to the recurring symptoms of lower urinary tract and genitalia. As the opinions about the etiology of CP are still not uniform, it is very difficult to be treated or even cured. Autophagy is a highly conserved physiological function which is widely found in eukaryotic cells. In general, cells maintain a certain level of autophagy under physiological conditions, and the basal level of autophagy can be regulated by a variety of autophagy-related genes under stress such as hunger, infection, trauma, and other circumstances...
April 19, 2018: Inflammation
Jing-Jing Zhang, Qin-Ming Zhou, Sheng Chen, Wei-Dong Le
AIMS: To investigate the effect and mechanisms of carbamazepine (CBZ) on the onset and progression of amyotrophic lateral sclerosis (ALS) in SOD1-G93A mouse model. METHODS: Starting from 64 days of age, SOD1-G93A mice were orally administered with CBZ at 200 mg/kg once daily until death. The disease onset and life span of SOD1-G93A mice were recorded. Motor neurons (MNs) in anterior horn of spinal cord were quantified by Nissl staining and SMI-32 immunostaining...
April 14, 2018: CNS Neuroscience & Therapeutics
Zhen-Yu Cai, Bo Yang, Ying-Xu Shi, Wei-Lin Zhang, Fei Liu, Wei Zhao, Mao-Wei Yang
Diabetes is a chronic disease that disrupts the balance between bone formation and bone desorption, which can lead to osteoporosis, increasing the risk of fracture. However, compared with osteoblasts, the biological effects of hyperglycemia on osteoclastogenesis remain to be elucidated. Therefore, we investigated the impact of glucose at different concentrations (5.5, 10.5, 15.5, 20.5, 25.5, and 30.5 mM) on osteoclastogenesis using RAW264.7 cells. Cell proliferation was measured with the cell counting kit-8 assay, and osteoclastogenesis was detected with tartrate-resistant acid phosphatase staining and bone resorption assays, as well as protein cathepsin K expression...
April 9, 2018: Biochemical and Biophysical Research Communications
Yan G Zhao, Nan Liu, Guangyan Miao, Yong Chen, Hongyu Zhao, Hong Zhang
The endoplasmic reticulum (ER) is the site of biogenesis of the isolation membrane (IM, autophagosome precursor) and forms extensive contacts with IMs during their expansion into double-membrane autophagosomes. Little is known about the molecular mechanism underlying the formation and/or maintenance of the ER/IM contact. The integral ER proteins VAPA and VAPB (VAPs) participate in establishing ER contacts with multiple membranes by interacting with different tethers. Here, we demonstrate that VAPs also modulate ER/IM contact formation...
March 31, 2018: Current Biology: CB
Zhao-Zhong Feng, An-Jie Jiang, An-Wen Mao, Yuhan Feng, Weinan Wang, Jingjing Li, Xiaoyan Zhang, Ke Xing, Xue Peng
In mammalian cells, autophagy plays crucial roles in restricting further spread of invading bacterial pathogens. Previous studies have established that the Salmonella virulence factors SseF and SseG are required for intracellular bacterial survival and replication. However, the underlying mechanism by which these two effectors facilitate bacterial infection remains elusive. Here, we report that SseF and SseG secreted by Salmonella Typhimurium (S. Typhimurium) inhibit autophagy in host cells and thereby establish a replicative niche for the bacteria in the cytosol...
April 2, 2018: Journal of Biological Chemistry
Carmela Fusco, Barbara Mandriani, Martina Di Rienzo, Lucia Micale, Natascia Malerba, Dario Cocciadiferro, Eva Sjøttem, Bartolomeo Augello, Gabriella Squeo, Maria Teresa Pellico, Ashish Jain, Terje Johansen, Gian Maria Fimia, Giuseppe Merla
Autophagy is a catabolic process needed for maintaining cell viability and homeostasis in response to numerous stress conditions. Emerging evidence indicates that the ubiquitin system has a major role in this process. TRIMs, an E3 ligase protein family, contribute to selective autophagy acting as receptors and regulators of the autophagy proteins recognizing endogenous or exogenous targets through intermediary autophagic tags, such as ubiquitin. Here we report that TRIM50 fosters the initiation phase of starvation-induced autophagy and associates with Beclin1, a central component of autophagy initiation complexes...
March 28, 2018: Biochimica et Biophysica Acta
Seung Taek Ji, Yeon-Ju Kim, Seok Yun Jung, Da Yeon Kim, Songhwa Kang, Ji Hye Park, Woong Bi Jang, Jongseong Ha, Jisoo Yun, Sang-Mo Kwon
Mesenchymal stem cells (MSCs) are multipotent progenitor cells with self-renewing properties; thus, transplanting functionally enhanced MSCs might be a promising strategy for cell therapy against ischemic diseases. However, extensive oxidative damage in ischemic tissue affects the cell fate of transplanted MSCs, eventually resulting in cell damage and autophagic cell death. Oleuropein (OLP) is a bioactive compound isolated from olives and olive oil that harbors antioxidant properties. This study aimed to investigate the potential cytoprotective effects of OLP against oxidative stress and autophagic cell death in MSCs...
March 28, 2018: Biochemical and Biophysical Research Communications
Ana Santos-Llamas, Maria J Monte, Jose J G Marin, Maria J Perez
The nucleoside reverse transcriptase inhibitor zidovudine (AZT), used in HIV infection treatment, induces mitochondrial DNA (mtDNA) depletion. A cause-effect relationship between mtDNA status alterations and autophagy has been reported. Both events are common in several liver diseases, including hepatocellular carcinoma. Here, we have studied autophagy activation in rat liver with mtDNA depletion induced by AZT administration in drinking water for 35 days. AZT at a concentration of 1 mg/ml, but not 0.5 mg/ml in the drinking water, decreased mtDNA levels in rat liver and extrahepatic tissues...
March 28, 2018: Archives of Toxicology
Wen Li, Shupeng Li, Yifang Li, Xiaoying Lin, Yongquan Hu, Tian Meng, Baojin Wu, Rongrong He, Du Feng
Immunofluorescence is an invaluable technique widely used in cell biology. This technique allows visualization of the subcellular distribution of different target proteins or organelles, by specific recognition of the antibody to the endogenous protein itself or to its antigen via the epitope. This technique can be used on tissue sections, cultured cells, or individual cells. Meanwhile, immunofluorescence can also be used in combination with non-antibody fluorescent staining, such as DAPI or fluorescent fusion proteins, e...
March 27, 2018: Methods in Molecular Biology
Abhishek Vats, Mandaville Gourie-Devi, Kavita Ahuja, Ankkita Sharma, Saima Wajid, Nirmal Kumar Ganguly, Vibha Taneja
Misfolded protein aggregates are the hallmark of Amyotrophic Lateral Sclerosis (ALS) which suggests involvement of protein homeostasis pathways in etiology of ALS. However, status of protein homeostasis in peripheral blood of ALS is not well established. We analyzed expression levels of key genes of proteostasis pathways in peripheral blood mononuclear cells (PBMCs) of sporadic ALS (sALS) patients and healthy controls. Increased protein carbonylation was observed in patients reflecting oxidative damage in PBMCs...
April 15, 2018: Journal of the Neurological Sciences
Claudia Manzoni, Adamantios Mamais, Sybille Dihanich, Marc P M Soutar, Helene Plun-Favreau, Rina Bandopadhyay, Rosella Abeti, Paola Giunti, John Hardy, Mark Cookson, Sharon A Tooze, Patrick A Lewis
Unc-51 Like Kinase 1 (ULK1) is a critical regulator of the biogenesis of autophagosomes, the central component of the catabolic macroautophagy pathway. Regulation of ULK1 activity is dependent upon several phosphorylation events acting to repress or activate the enzymatic function of this protein. Phosphorylation of Ser758 ULK1 has been linked to repression of autophagosome biogenesis and was thought to be exclusively dependent upon mTOR complex 1 kinase activity. In this study, a novel regulation of Ser758 ULK1 phosphorylation is reported following prolonged inhibition of the Parkinson's disease linked protein Leucine Rich Repeat Kinase 2 (LRRK2)...
March 21, 2018: Bioscience Reports
Liang Ouyang, Lan Zhang, Shouyue Zhang, Dahong Yao, Yuqian Zhao, Guan Wang, Leilei Fu, Peng Lei, Bo Liu
UNC-51-like kinase 1 (ULK1), the yeast Atg1 ortholog, is the sole serine-threonine kinase and initiating enzyme in autophagy, which may be regarded as a target in Parkinson's disease (PD). Herein, we discovered a small molecule 33i (BL-918) as a potent activator of ULK1 by structure-based drug design. Subsequently, some key amino acid residues (Arg18, Lys50, Asn86 and Tyr89) were found to be crucial to the binding pocket between ULK1 and 33i by site-directed mutagenesis. Moreover, we found that 33i induced autophagy via the ULK complex in SH-SY5Y cells...
March 21, 2018: Journal of Medicinal Chemistry
Eun Jeong Jang, Sang Chan Kim, Ju-Hee Lee, Jong Rok Lee, Il Kon Kim, Su Youn Baek, Young Woo Kim
BACKGROUND: Laminaria japonica has frequently been used as a food supplement and drug in traditional oriental medicine. Among the major active constituents responsible for the bioactivities of L. japonica, fucoxanthin (FX) has been considered as a potential antioxidant. This study was conducted to examine the effects of L. japonica extract (LJE) or FX against oxidative stress on hepatocytes and to elucidate the overall their cellular mechanisms of the effects. METHODS: We constructed an in vitro model with the treatment of arachidonic acid (AA) + iron in HepG2 cells to stimulate the oxidative damage...
March 20, 2018: BMC Complementary and Alternative Medicine
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
Jie Hao, Shuangyue Li, Xiaoxia Shi, Zhiqiang Qian, Yijie Sun, Dunjia Wang, Xueying Zhou, Hongxin Qu, Shuhai Hu, Enjun Zuo, Cong Zhang, Liyan Hou, Qingshan Wang, Fengyuan Piao
Chronic exposure to n-hexane, a widely used organic solvent in industry, induces central-peripheral neuropathy, which is mediated by its active metabolite, 2,5-hexanedione (HD). We recently reported that transplantation of bone marrow-mesenchymal stem cells (BMSC) significantly ameliorated HD-induced neuronal damage and motor deficits in rats. However, the mechanisms remain unclear. Here, we reported that inhibition of HD-induced autophagy contributed to BMSC-afforded protection. BMSC transplantation significantly reduced the levels of microtubule-associated protein 1 light chain 3-II (LC3-II) and the degradation of sequestosome-1 (p62) in the spinal cord and sciatic nerve of HD-intoxicated rats...
March 14, 2018: Scientific Reports
Zezhu Zhou, Guixun Shi, Xinfeng Zheng, Shengdan Jiang, Leisheng Jiang
Autophagy has been indicated to be involved in regulating bone metabolism. However, little is known about the role of autophagy in mechanical stimulation-influenced osteoblast differentiation and bone formation. In the present study, we first demonstrated that autophagy activation was essential for cyclic mechanical stretching-promoted osteoblast differentiation of bone marrow mesenchymal stem cells. To explore the in vivo role of autophagy in osteoblast differentiation, the hindlimb unloading-induced disuse osteoporosis model was used...
March 7, 2018: Biochemical and Biophysical Research Communications
Qi Wang, Li-Wen Wei, Wen-Tao Zhou, Zheng-Tao Wang, Xiao-Li Xie
Hepatotoxicity is one of the adverse health effects induced by polychlorinated biphenyls (PCBs). Recently, autophagy was revealed to play an important role in PCBs-induced toxicology, however, its precise role in PCBs-induced hepatotoxicity is as yet unknown. In this study, treatment of PCB28/PCB52 for 48 h dose-dependently induced hepatotoxicity at doses of 10, 20, 40 and 80 μM in homo and rattus hepatocytes. Expressions of proteins of BECN1, LC3-II and ULK1 significantly increased in PCB28/PCB52-treated cells at a dose of 40 μM, implying initiation of autophagy...
March 5, 2018: Toxicology Letters
Chao Wang, Zhongyang Yu, Xiaochen Shi, Xudong Tang, Yang Wang, Xueyan Wang, Yanan An, Shulin Li, Yan Li, Xuefei Wang, Wenjing Luan, Zhaobin Chen, Mingyuan Liu, Lu Yu
Triclosan (TCS) is a broad-spectrum antimicrobial agent, whose well-known antibacterial mechanism is inhibiting lipid synthesis. Autophagy, an innate immune response, is an intracellular process that delivers the cargo including pathogens to lysosomes for degradation. In this study, we first demonstrated that TCS induced autophagy in a dose-dependent manner in non-phagocytic cells (HeLa) and in macrophages (Raw264.7) and in vivo . The western blot results also revealed that TCS induced autophagy via the AMPK/ULK1 and JNK/ERK/p38 pathways independent of mTOR...
2018: Frontiers in Cellular and Infection Microbiology
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
Yufeng Li, Zhiwei Liu, Yiqian Zhang, Qixiang Zhao, Xiaoyu Wang, Peng Lu, Hao Zhang, Zhu Wang, Hongyan Dong, Zhongming Zhang
Pigment epithelial-derived factor (PEDF) is known to exert diverse physiological activities. Previous studies suggest that hypoxia could induce mitophagy. Astoundingly, under hypoxic condition, we found that PEDF decreased the mitochondrial density of cardiomyocytes. In this study, we evaluated whether PEDF could decrease the mitochondrial density and play a protective role in hypoxic cardiomyocytes via promoting mitophagy. Immunostaining and western blotting were used to analyze mitochondrial density and mitophagy of hypoxic cardiomyocytes...
March 6, 2018: International Journal of Molecular Medicine
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