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https://www.readbyqxmd.com/read/28528366/cdk5-mediated-phosphorylation-dependent-ubiquitination-and-degradation-of-e3-ubiquitin-ligases-gp78-accelerates-neuronal-death-in-parkinson-s-disease
#1
Qingzhi Wang, Fengjuan Jiao, Pei Zhang, Jianguo Yan, Zheng Zhang, Feng He, Qian Zhang, Zexi Lv, Xiang Peng, Hongwei Cai, Bo Tian
The molecular mechanisms responsible for the loss of dopaminergic neurons in Parkinson's disease (PD) remain obscure. Loss of function of E3 ubiquitin ligases is associated with mitochondria dysfunction, dysfunction of protein degradation, and α-synuclein aggregation, which are major contributors to neurodegeneration in PD. Recent research has thus focused on E3 ubiquitin ligase glycoprotein 78 (GP78); however, the role of GP78 in PD pathogenesis remains unclear. Notably, cyclin-dependent kinase 5 (CDK5) controls multiple cellular events in postmitotic neurons, and CDK5 activity has been implicated in the pathogenesis of PD...
May 20, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28522852/kv3-4-is-modulated-by-hif-1%C3%AE-to-protect-sh-sy5y-cells-against-oxidative-stress-induced-neural-cell-death
#2
Min Seok Song, Pan Dong Ryu, So Yeong Lee
The Kv3.4 channel is characterized by fast inactivation and sensitivity to oxidation. However, the physiological role of Kv3.4 as an oxidation-sensitive channel has yet to be investigated. Here, we demonstrate that Kv3.4 plays a pivotal role in oxidative stress-related neural cell damage as an oxidation-sensitive channel and that HIF-1α down-regulates Kv3.4 function, providing neuroprotection. MPP(+) and CoCl2 are reactive oxygen species (ROS)-generating reagents that induce oxidative stress. However, only CoCl2 decreases the expression and function of Kv3...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28521299/isradipine-attenuates-mptp-induced-dopamine-neuron-degeneration-by-inhibiting-up-regulation-of-l-type-calcium-channels-and-iron-accumulation-in-the-substantia-nigra-of-mice
#3
Qi-Min Wang, Yu-Yu Xu, Shang Liu, Ze-Gang Ma
The aim of this study is to investigate the effects of L-type calcium channels (LTCCs) on MPTP-induced dopamine (DA) neuron degeneration and iron accumulation in the substantia nigra (SN) of mice. By real-time PCR and western blots, we first quatified expressions of L-type Cav1.2 and Cav1.3 calcium channel α1 subunits in the SN of experimental mice treated with MPTP. We found that the expressions of Cav1.2 and Cav1.3 calcium channel α1 subunits markedly increased after MPTP treatment for 2 and 3 weeks. Secondly, we observed the effects of isradipine, a LTCC antagonist, on MPTP-induced DA neuron degeneration and iron accumulation in the SN...
May 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28517367/rationale-and-design-of-a-randomized-trial-to-assess-the-safety-and-efficacy-of-multipoint-pacing-mpp-in-cardiac-resynchronization-therapy-the-mpp-trial
#4
Gery Tomassoni, James Baker, Raffaele Corbisiero, Charles Love, David Martin, Robert Sheppard, Seth J Worley, Kwangdeok Lee, Imran Niazi
BACKGROUND: Although the majority of Class III congestive heart failure (HF) patients treated with cardiac resynchronization therapy (CRT) show a clinical benefit, up to 40% of patients do not respond to CRT. This paper reports the design of the MultiPoint Pacing (MPP) trial, a prospective, randomized, double-blind, controlled study to evaluate the safety and efficacy of CRT using MPP compared to standard biventricular (Bi-V) pacing. METHODS: A maximum of 506 patients with a standard CRT-D indication will be enrolled at up to 50 US centers...
May 18, 2017: Annals of Noninvasive Electrocardiology
https://www.readbyqxmd.com/read/28511916/pre-treatment-with-amitriptyline-causes-epigenetic-up-regulation-of-neuroprotection-associated-genes-and-has-anti-apoptotic-effects-in-mouse-neuronal-cells
#5
Nguyen Quoc Vuong Tran, An Nghia Nguyen, Kyoko Takabe, Zentaro Yamagata, Kunio Miyake
Antidepressants, such as imipramine and fluoxetine, are known to alter gene expression patterns by inducing changes in the epigenetic status of neuronal cells. There is also some evidence for the anti-apoptotic effect of various groups of antidepressants; however, this effect is complicated and cell-type dependent. Antidepressants of the tricyclic group, in particular amitriptyline, have been suggested to be beneficial in the treatment of neurodegenerative disorders. We examined whether amitriptyline exerts an anti-apoptotic effect via epigenetic mechanisms...
May 13, 2017: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/28501872/a-mechanism-study-underlying-the-protective-effects-of-cyclosporine-a-on-lung-ischemia-reperfusion-injury
#6
Jian''an Li, Zhongya Yan, Qianjin Fang
AIM: This study is aimed at validating the hypothesis that administration of cyclosporine-A (CsA) would be protective in lung ischemia-reperfusion (I/R) injury and in exploring the underlying mechanism. METHODS: Rabbits were divided into 4 groups: the control, sham operation, I/R, and I/R with CsA treatment. Flow cytometry was used to measure the mitochondrial membrane potential. Laser scanning confocal microscope was used to analyze mitochondrion permeability transition pore (MPTP)...
May 10, 2017: Pharmacology
https://www.readbyqxmd.com/read/28494419/neuroprotective-effects-of-total-flavonoid-fraction-of-the-epimedium-koreanum-nakai-extract-on-dopaminergic-neurons-in-vivo-and-in-vitro
#7
Lin Wu, Zhong-Rui Du, Ai-Li Xu, Zhen Yan, Hui-Hui Xiao, Man-Sau Wong, Xin-Sheng Yao, Wen-Fang Chen
Flavonoids, the active components of Epimedii Genus, have been demonstrated to protect against osteoporosis, cardiovascular diseases and rheumatoid arthritis. The present study aimed to investigate the neuroprotective effects of total flavonoid (TF) fraction of Epimedium koreanum Nakai on dopaminergic neurons in the cellular and mice models of Parkinson's disease (PD). TF pretreatment could ameliorate the decrease of striatal dopamine (DA) content and the loss of tyrosine hydroxylase (TH)-immunoreactive neurons in the substantia nigra pars compacta (SNpc) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)...
May 8, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28484287/mir-135b-plays-a-neuroprotective-role-by-targeting-gsk3%C3%AE-in-mpp-intoxicated-sh-sy5y-cells
#8
Jianlei Zhang, Wei Liu, Yabo Wang, Shengnan Zhao, Na Chang
miR-135a-5p was reported to play a crucial role in the protective effects of hydrogen sulfide against Parkinson's disease (PD) by targeting rho-associated protein kinase 2 (ROCK2). However, the role of another member of miR-135 family (miR-135b) and the underlying mechanism in PD are still unclear. qRT-PCR and western blot showed that miR-135 was downregulated and glycogen synthase kinase 3β (GSK3β) was upregulated at mRNA and protein levels in MPP(+)-intoxicated SH-SY5Y cells in a dose- and time-dependent manner...
2017: Disease Markers
https://www.readbyqxmd.com/read/28481321/atractylenolide-i-protects-human-sh-sy5y-cells-from-1-methyl-4-phenylpyridinium-induced-apoptotic-cell-death
#9
Sandeep Vasant More, Dong-Kug Choi
Oxidative stress and apoptosis are the major mechanisms that induce dopaminergic cell death. Our study investigates the protective effects of atractylenolide-I (ATR-I) on 1-methyl-4-phenylpyridinium (MPP⁺)-induced cytotoxicity in human dopaminergic SH-SY5Y cells, as well as its underlying mechanism. Our experimental data indicates that ATR-I significantly inhibits the loss of cell viability induced by MPP⁺ in SH-SY5Y cells. To further unravel the mechanism, we examined the effect of ATR-I on MPP⁺-induced apoptotic cell death characterized by an increase in the Bax/Bcl-2 mRNA ratio, the release of cytochrome-c, and the activation of caspase-3 leading to elevated levels of cleaved poly(ADP-ribose) polymerase (PARP) resulting in SH-SY5Y cell death...
May 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28474543/neuroprotective-effects-of-citrus-fruit-derived-flavonoids-nobiletin-and-tangeretin-in-alzheimer-s-and-parkinson-s-disease
#10
Nady Braidy, Sahar Behzad, Solomon Habtemariam, Touqeer Ahmed, Maria Daglia, Seyed Mohammad Nabavi, Eduardo Sobarzo-Sanchez, Seyed Fazel Nabavi
Neurodegenerative diseases, namely Alzheimer`s disease and Parkinson's disease represent a deleterious impact worldwide. Despite extensive preclinical and clinical research in neurodegenerative disorders, therapeutic strategies aimed at the prevention and chronic treatment of neurodegenerative conditions have not been successfully translated to the clinic. Therefore, the identification of novel pharmacological intervention derived from natural products is warranted. Nobiletin and tangeretin are important citrus flavonoids derived from the peel and other parts of Citrus L...
March 27, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28472770/modeling-african-american-prostate-adenocarcinoma-by-inducing-defined-genetic-alterations-in-organoids
#11
Kenji Unno, Meejeon Roh, Young A Yoo, Yousef Al-Shraideh, Lu Wang, Larisa Nonn, Sarki A Abdulkadir
Genomic studies are rapidly identifying genetic alterations in human cancer, but functional validation of such alterations has been slow. Here, using human prostate cancer as a model, we have assessed the feasibility of engineering defined genetic alterations in well-known cancer driver genes to transform benign prostate epithelial organoids derived from African American men. Benign human prostate organoids were transduced with lentiviruses expressing MYC, shPTEN, shTP53 and AR, alone and in various combinations, to recapitulate prostate cancer development...
April 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28468613/low-mean-perfusion-pressure-is-a-risk-factor-for-progression-of-acute-kidney-injury-in-critically-ill-patients-a-retrospective-analysis
#12
Marlies Ostermann, Anna Hall, Siobhan Crichton
BACKGROUND: The aim was to investigate whether mean perfusion pressure (MPP) calculated as the difference between mean arterial pressure (MAP) and central venous pressure (CVP) was associated with risk of progression from AKI I to AKI III in critically ill patients. METHODS: Retrospective analysis of adult patients admitted to a multi-disciplinary adult intensive care unit (ICU) between July 2007 and June 2009 who developed AKI I and in whom advanced haemodynamic monitoring was initiated within 12 h of diagnosis of AKI I...
May 3, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28454745/retina-to-blood-transport-of-1-methyl-4-phenylpyridinium-mpp-involves-carrier-mediated-process-at-the-blood-retinal-barrier
#13
Yoshiyuki Kubo, Masakazu Yamamoto, Kensuke Matsunaga, Takuya Usui, Shin-Ichi Akanuma, Ken-Ichi Hosoya
1-Methyl-4-phenylpyridinium (MPP(+)) transport at the blood-retinal barrier (BRB) was investigated. The retinal uptake index (RUI) estimated for [(3)H]MPP(+) was similar to that of [(3)H]D-mannitol, and was insensitive to unlabeled MPP(+), suggesting no positive evidence to support the involvement of carrier-mediated transport in the blood-to-retina transport of MPP(+) at the BRB. A microdialysis investigation showed that the concentration of [(3)H]MPP(+) in the vitreous humor decreased in a biexponential manner, and the rate constant for [(3)H]MPP(+) elimination during terminal phase was greater than that of [(14)C]D-mannitol...
April 25, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28450223/gper-activation-is-effective-in-protecting-against-inflammation-induced-nigral-dopaminergic-loss-and-motor-function-impairment
#14
Julieta Mendes-Oliveira, Filipa Lopes Campos, Rita Alexandra Videira, Graça Baltazar
Increasing evidence suggest that excessive inflammatory responses from overactivated microglia play a critical role in Parkinson's disease (PD), contributing to, or exacerbating, nigral dopaminergic (DA) degeneration. Recent results from our group and others demonstrated that selective activation of G protein-coupled estrogen receptor (GPER) with the agonist G1 can protect DA neurons from 1-methyl-4-phenylpyridinium (MPP+) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxins. However, it is not known whether modulation of microglial responses is one of the mechanisms by which G1 exerts its DA neuroprotective effects...
April 24, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28445933/the-long-noncoding-rna-hotair-promotes-parkinson-s-disease-by-upregulating-lrrk2-expression
#15
Sheng Wang, Xuan Zhang, Yuanyuan Guo, Han Rong, Tiebang Liu
Long noncoding RNAs (lncRNAs) have emerged recently as a new class of genes that regulate cellular processes. HOTAIR (Hox transcript antisense intergenic RNA), an approximately 2.2 kb long noncoding RNA transcribed from the HOXC locus, is upregulated in various diseases. However, the role of HOTAIR in Parkinson's disease (PD) remains unclear. A mouse model of PD was developed by intraperitoneal injection of MPTP. The expression of HOTAIR and LRRK2 were detected in the PD mice and in human neuroblastoma cell lines SH-SY5Y pretreated with MPP+...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28443637/mild-mpp-exposure-induced-glucose-starvation-enhances-autophagosome-synthesis-and-impairs-its-degradation
#16
Shuichiro Sakamoto, Masatsugu Miyara, Seigo Sanoh, Shigeru Ohta, Yaichiro Kotake
Parkinson's disease (PD) is a prevalent neurodegenerative disorder, mainly characterised by the progressive loss of dopaminergic neurons. MPP(+) has been widely used as a PD-related neurotoxin, and their reports suggested the several hypotheses for neuronal cell death. However, most of these hypotheses come from the studies about the acute MPP(+) exposure. We previously revealed that mild MPP(+) exposure (10 and 200 μM), which induces gradual cell death, impairs autophagosome degradation at 48 h. In the present study, we further investigated the specific events of mild MPP(+) exposure and revealed that mild MPP(+) exposure causes the cell death through glucose starvation, but not acute toxic model (2...
April 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28442990/spatiotemporal-and-long-lasting-modulation-of-11-key-nogo-signaling-genes-in-response-to-strong-neuroexcitation
#17
Tobias E Karlsson, Katrin Wellfelt, Lars Olson
Inhibition of nerve growth and plasticity in the CNS is to a large part mediated by Nogo-like signaling, now encompassing a plethora of ligands, receptors, co-receptors and modulators. Here we describe the distribution and levels of mRNA encoding 11 key genes involved in Nogo-like signaling (Nogo-A, Oligodendrocyte-Myelin glycoprotein (OMgp), Nogo receptor 1 (NgR1), NgR2, NgR3, Lingo-1, TNF receptor orphan Y (Troy), Olfactomedin, Lateral olfactory tract usher substance (Lotus) and membrane-type matrix metalloproteinase-3 (MT3-MPP)), as well as BDNF and GAPDH...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28442376/copper-sulfate-pretreatment-prevents-mitochondrial-electron-transport-chain-damage-and-apoptosis-against-mpp-induced-neurotoxicity
#18
Moisés Rubio-Osornio, Marisol Orozco-Ibarra, Araceli Díaz-Ruiz, Eduardo Brambila, Marie-Catherine Boll, Antonio Monroy-Noyola, Jorge Guevara, Sergio Montes, Camilo Ríos
Intrastriatal injection of 1-methyl-4-phenylpyridinium (MPP(+)) is considered a model to reproduce some biochemical alterations observed in Parkinson's disease (PD) patients. Among those alterations, inhibition of mitochondrial complex I activity, increased free radical production and reduced antioxidant responses have been reported. Copper (Cu) plays an important role in the metabolism and antioxidative responses through its participation as a cofactor in the cytochrome c oxidase enzyme (COX), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), and metallothioneins...
April 22, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28440831/systematic-investigations-on-fused-%C3%AF-system-compounds-of-seven-benzene-rings-prepared-by-photocyclization-of-diphenanthrylethenes
#19
Shota Fujino, Minoru Yamaji, Hideki Okamoto, Toshiki Mutai, Isao Yoshikawa, Hirohiko Houjou, Fumito Tani
We studied the photoproducts of 1-(n-phenanthryl)-2-(m-phenanthryl)ethenes (nEm; n, m = 1, 3 and 9) for understanding photocyclization patterns based on NMR spectroscopy. The crystal structures of the photoproducts were analyzed by X-ray crystallography, and the photophysical features of the photocyclized molecules were investigated based on emission and transient absorption measurements. Phenanthrene derivatives substituted at the 1- and 3-positions were prepared for synthesizing nEm by photocyclization of stilbene derivatives...
April 25, 2017: Photochemical & Photobiological Sciences
https://www.readbyqxmd.com/read/28439401/long-non-coding-rna-malat1-contributes-to-cell-apoptosis-by-sponging-mir-124-in-parkinson-disease
#20
Wei Liu, Qishun Zhang, Jianlei Zhang, Wujun Pan, Jingya Zhao, Yuming Xu
BACKGROUND: Parkinson disease (PD) is the most common movement disturbance characterized by the loss of dopaminergic (DA) neurons in midbrain. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is aberrantly expressed in neurons and is involved in the dendritic and synapse development. However, the role of MALAT1 and its underlying mechanism in PD remain to be defined. METHODS: The expressions of MALAT1 and miR-124 were evaluated by qRT-PCR. N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice and SH-SY5Y cells subjected to N-methyl-4-phenylpyridinium (MPP(+)) were utilized to investigate the effect of MALAT1 on PD...
2017: Cell & Bioscience
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