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https://www.readbyqxmd.com/read/28092019/urb597-and-the-cannabinoid-win55-212-2-reduce-behavioral-and-neurochemical-deficits-induced-by-mptp-in-mice-possible-role-of-redox-modulation-and-nmda-receptors
#1
Angel Escamilla-Ramírez, Esperanza García, Guadalupe Palencia-Hernández, Ana Laura Colín-González, Sonia Galván-Arzate, Isaac Túnez, Julio Sotelo, Abel Santamaría
Several physiological events in the brain are regulated by the endocannabinoid system (ECS). While synthetic cannabinoid receptor (CBr) agonists such as WIN55,212-2 act directly on CBr, agents like URB597, a fatty acid amide hydrolase (FAAH) inhibitor, induce a more "physiological" activation of CBr by increasing the endogenous levels of the endocannabinoid anandamide (AEA). Herein, we compared the pre- and post-treatment efficacy of URB597 and WIN55,212-2 on different endpoints evaluated in the toxic model produced by the mitochondrial toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice...
January 14, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28089921/penehyclidine-hydrochloride-prevents-anoxia-reoxygenation-injury-and-induces-h9c2-cardiomyocyte-apoptosis-via-a-mitochondrial-pathway
#2
Zhaoqi Wang, Duomao Lin, Liang Zhang, Wenjun Liu, Hongbao Tan, Jun Ma
Penehyclidine hydrochloride (PHC) is an anticholinergic drug that has been widely used in the clinic for years, evaluating for anesthetic premedication, anti-muscarinic, or improving microcirculation. However, very little is known about its protective effects against anoxia/reoxygenation (A/R) injury in myocardiocytes. The aim of our study was to investigate the protective effects of PHC pretreatment on A/R injury, as well as the underlying mechanisms involved. To investigate apoptosis, we used the cell viability assay, Annexin-V/PI assay, and lactate dehydrogenase (LDH) and creatine kinase (CK) activity measurements...
January 12, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28078613/l-f001-a-multifunction-rock-inhibitor-prevents-6-ohda-induced-cell-death-through-activating-akt-gsk-3beta-and-nrf2-ho-1-signaling-pathway-in-pc12-cells-and-attenuates-mptp-induced-dopamine-neuron-toxicity-in-mice
#3
Liting Luo, Jingkao Chen, Dan Su, Meihui Chen, Bingling Luo, Rongbiao Pi, Lan Wang, Wei Shen, Rikang Wang
Amounting evidences demonstrated that Rho/Rho-associated kinase (ROCK) might be a novel target for the therapy of Parkinson's disease (PD). Recently, we synthesized L-F001 and revealed it was a potent ROCK inhibitor with multifunctional effects. Here we investigated the effects of L-F001 in PD models. We found that L-F001 potently attenuated 6-OHDA-induced cytotoxicity in PC12 cells and significantly decreased intracellular reactive oxygen species (ROS), prevented the 6-OHDA-induced decline of mitochondrial membrane potential and intracellular GSH levels...
January 11, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28065786/cisplatin-induced-necroptosis-in-tnf%C3%AE-dependent-and-independent-pathways
#4
Yanfang Xu, Hua-Bin Ma, Yu-Lu Fang, Zhi-Rong Zhang, Jing Shao, Mao Hong, Chao-Jun Huang, Jing Liu, Rui-Qing Chen
Cisplatin is a chemotherapeutic drug for treatment of many solid tumors. It has been shown to induce apoptosis and/or necrosis in different types of cancer cells. However, the underlying mechanisms remain elusive. In this study, we provide evidences that cisplatin induces necroptosis in receptor-interacting protein 3 (RIP3)-expressing cell lines, but not in cell lines lacking RIP3 protein expression. Deficiency of core components of necroptotic pathway, RIP1, RIP3, or mixed lineage kinase domain-like protein (MLKL) blocked cisplatin-induced cell death in L929 cells...
January 6, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28064403/knockdown-of-clusterin-alters-mitochondrial-dynamics-facilitates-necrosis-in-camptothecin-induced-cancer-stem-cells
#5
Parthasarathy Arumugam, Annie Samson, Jieun Ki, Joon Myong Song
The existence of a well-established drug resistance mechanism in cancer stem cells (CSC) complicates the cancer treatment. Clusterin (CLU) plays a key role in maintaining the integrity of endoplasmic reticulum (ER) during drug-induced stress. Hence, silencing the CLU could significantly reduce the inherent drug resistance mechanism of CSC. The combination of drug-induced cytotoxicity, as well as the suppression of drug resistance in CSC, could circumvent the recurrence capability of the tumor. In the present study, camptothecin (CPT)-induced apoptosis and necrosis in CSC with and without siCLU treatment were simultaneously measured using Qdot-based total internal reflection fluorescence microscope (TIRF)...
January 7, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28062948/low-levels-of-prohibitin-in-substantia-nigra-makes-dopaminergic-neurons-vulnerable-in-parkinson-s-disease
#6
Debashis Dutta, Nilufar Ali, Emili Banerjee, Raghavendra Singh, Amit Naskar, Ramesh Kumar Paidi, Kochupurackal P Mohanakumar
Since substantia nigra (SN) and ventral tegmental area (VTA) dopaminergic neurons are, respectively, susceptible or largely unaffected in Parkinson's disease (PD), we searched for protein(s) that regulates this differential sensitivity. Differentially, expressed proteins in SN and VTA were investigated employing two-directional gel electrophoresis- matrix-assisted laser desorption ionization time of flight (MALDI-TOF-TOF) analyses. Prohibitin, which is involved in mitochondrial integrity, was validated using immunoblot, qRT-PCR, and immunohistochemistry in normal mice as well as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-model, PD postmortem human brains, and PD cybrids...
January 6, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28062370/treadmill-exercise-alleviates-motor-deficits-and-improves-mitochondrial-import-machinery-in-an-mptp-induced-mouse-model-of-parkinson-s-disease
#7
Jung-Hoon Koo, Joon-Yong Cho, Ung-Bae Lee
Alpha-synuclein (α-Syn) accumulation is significantly correlated with motor deficits and mitochondrial dysfunction in Parkinson's disease (PD), but the molecular mechanism underlying its pathogenesis is unclear. In this study, we investigated the effects of treadmill exercise on motor deficits and mitochondrial dysfunction in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Treadmill exercise inhibited dopaminergic neuron loss by promoting the expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT) and seemed to improve cell survival by reducing α-Syn expression...
January 3, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28060896/isobavachalcone-attenuates-mptp-induced-parkinson-s-disease-in-mice-by-inhibition-of-microglial-activation-through-nf-%C3%AE%C2%BAb-pathway
#8
Haoran Jing, Shaoxia Wang, Min Wang, Wenliang Fu, Chao Zhang, Donggang Xu
Parkinson's disease (PD) is a complex multi-system and age-related neurodegenerative disorder. The intervention targeting neuroinflammation in PD patients is one effective strategy to slow down or inhibit disease progression. Microglia-mediated inflammatory response plays an important role in Parkinson's, Alzheimer's and other cerebral diseases. Isobavachalcone is a main component of Chinese herb medicine Psoralea corylifolia, which function includes immunoregulation, anti-oxidation and the regulation of β-amyloid (Aβ42) deposited in hippocampus in Alzheimer's patients...
2017: PloS One
https://www.readbyqxmd.com/read/28060833/wnt-signaling-prevents-the-a%C3%AE-oligomer-induced-mitochondrial-permeability-transition-pore-opening-preserving-mitochondrial-structure-in-hippocampal-neurons
#9
Macarena S Arrázola, Eva Ramos-Fernández, Pedro Cisternas, Daniela Ordenes, Nibaldo C Inestrosa
Alzheimer's disease (AD) is a neurodegenerative disorder mainly known for synaptic impairment and neuronal cell loss, affecting memory processes. Beside these damages, mitochondria have been implicated in the pathogenesis of AD through the induction of the mitochondrial permeability transition pore (mPTP). The mPTP is a non-selective pore that is formed under apoptotic conditions, disturbing mitochondrial structure and thus, neuronal viability. In AD, Aβ oligomers (Aβos) favor the opening of the pore, activating mitochondria-dependent neuronal cell death cascades...
2017: PloS One
https://www.readbyqxmd.com/read/28053825/bioactive-flavonoids-and-catechols-as-hif1-and-nrf2-protein-stabilizers-implications-for-parkinson-s-disease
#10
Natalya A Smirnova, Navneet Ammal Kaidery, Dmitry M Hushpulian, Ilay I Rakhman, Andrey A Poloznikov, Vladimir I Tishkov, Saravanan S Karuppagounder, Irina N Gaisina, Anton Pekcec, Klaus Van Leyen, Sergey V Kazakov, Lichuan Yang, Bobby Thomas, Rajiv R Ratan, Irina G Gazaryan
Flavonoids are known to trigger the intrinsic genetic adaptive programs to hypoxic or oxidative stress via estrogen receptor engagement or upstream kinase activation. To reveal specific structural requirements for direct stabilization of the transcription factors responsible for triggering the antihypoxic and antioxidant programs, we studied flavones, isoflavones and catechols including dihydroxybenzoate, didox, levodopa, and nordihydroguaiaretic acid (NDGA), using novel luciferase-based reporters specific for the first step in HIF1 or Nrf2 protein stabilization...
December 2016: Aging and Disease
https://www.readbyqxmd.com/read/28042095/reduced-noradrenergic-innervation-of-ventral-midbrain-dopaminergic-cell-groups-and-the-subthalamic-nucleus-in-mptp-treated-parkinsonian-monkeys
#11
Gunasingh Jeyaraj Masilamoni, Olivia Groover, Yoland Smith
There is anatomical and functional evidence that ventral midbrain dopaminergic (DA) cell groups and the subthalamic nucleus (STN) receive noradrenergic innervation in rodents, but much less is known about these interactions in primates. Degeneration of NE neurons in the locus coeruleus (LC) and related brainstem NE cell groups is a well-established pathological feature of Parkinson's disease (PD), but the development of such pathology in animal models of PD has been inconsistent across species and laboratories...
December 30, 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/28034298/effective-agents-targeting-the-mitochondria-and-apoptosis-to-protect-the-heart
#12
Eltyeb Abdelwahid, Aurimas Stulpinas, Audrone Kalvelyte
A wide variety of agents have been traditionally used in cardiovascular medicine worldwide and their precise mechanisms of action have been demonstrated to be largely related to the cardiomyocyte mitochondria and apoptosis. Abnormalities in the structure and function of the mitochondria and mutations in mitochondrial DNA can decrease energy production, alter the redox system, impair calcium homeostasis, and induce the mitochondrial permeability transition pore (MPTP), causing cell death. All of these data provide evidence of mitochondrial signaling pathways as targets to downregulate cardiac cell apoptosis and thus to prevent and treat cardiovascular diseases...
December 29, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28033580/extracellular-cl-free-induced-cardioprotection-against-hypoxia-reoxygenation-is-associated-with-attenuation-of-mitochondrial-permeability-transition-pore
#13
Xian-Gui Zhang, Le Zhao, Yi Zhang, Yuan-Yuan Li, Huan Wang, Guang-Ling Duan, Lin Xiao, Xiao-Ran Li, He-Ping Chen
The isotonic substitution of extracellular chloride by gluconate (extracellular Cl(-)-free) has been demonstrated to elicit cardioprotection by attenuating ischaemia/reperfusion-induced elevation of intracellular chloride ion concentration ([Cl(-)]i). However, the downstream mechanism underlying the cardioprotective effect of extracellular Cl(-)-free is not fully established. Here, it was investigated whether extracellular Cl(-)-free attenuates mitochondrial dysfunction after hypoxia/reoxygenation (H/R) and whether mitochondrial permeability transition pore (mPTP) plays a key role in the extracellular Cl(-)-free cardioprotection...
December 26, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28028868/neurometabolic-profiles-of-the-substantia-nigra-and-striatum-of-mptp-intoxicated-common-marmosets-an-in-vivo-proton-mrs-study-at-9-4%C3%A2-t
#14
Hwon Heo, Jae-Bum Ahn, Hyeong Hun Lee, Euna Kwon, Jun-Won Yun, Hyeonjin Kim, Byeong-Cheol Kang
Given the strong coupling between the substantia nigra (SN) and striatum (STR) in the early stage of Parkinson's disease (PD), yet only a few studies reported to date that have simultaneously investigated the neurochemistry of these two brain regions in vivo, we performed longitudinal metabolic profiling in the SN and STR of 1-methyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated common marmoset monkey models of PD (n = 10) by using proton MRS ((1) H-MRS) at 9.4 T. T2 relaxometry was also performed in the SN by using MRI...
December 28, 2016: NMR in Biomedicine
https://www.readbyqxmd.com/read/28025713/cyclic-adp-ribose-as-an-endogenous-inhibitor-of-the-mtor-pathway-downstream-of-dopamine-receptors-in-the-mouse-striatum
#15
Haruhiro Higashida, Shin-Ya Kamimura, Takeshi Inoue, Osamu Hori, Mohammad Saharul Islam, Olga Lopatina, Chiharu Tsuji
The role of cyclic ADP-ribose (cADPR) as a second messenger and modulator of the mTOR pathway downstream of dopamine (DA) receptors and/or CD38 was re-examined in the mouse. ADP-ribosyl activity was low in the membranes of neonates, but DA stimulated it via both D1- and D2-like receptors. ADP-ribosyl cyclase activity increased significantly during development in association with increased expression of CD38. The cADPR binding proteins, FKBP12 and FKBP12.6, were expressed in the adult mouse striatum. The ratio of phosphorylated to non-phosphorylated S6 kinase (S6K) in whole mouse striatum homogenates decreased after incubation of adult mouse striatum with extracellular cADPR for 5 min...
December 26, 2016: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28019657/the-melanoma-linked-redhead-mc1r-influences-dopaminergic-neuron-survival
#16
Xiqun Chen, Hongxiang Chen, Waijiao Cai, Michael Maguire, Bailiu Ya, Fuxing Zuo, Robert Logan, Hui Li, Katey Robinson, Charles R Vanderburg, Yang Yu, Yinsheng Wang, David E Fisher, Michael A Schwarzschild
OBJECTIVE: Individuals with Parkinson's disease are more likely to develop melanoma, and melanoma patients are reciprocally at higher risk of developing Parkinson's disease. Melanoma is strongly tied to red hair/fair skin, a phenotype of loss-of-function polymorphisms in the MC1R (melanocortin 1 receptor) gene. Loss-of-function variants of MC1R have also been linked to increased risk of Parkinson's disease. The present study is to investigate the role of MC1R in dopaminergic neurons in vivo...
December 26, 2016: Annals of Neurology
https://www.readbyqxmd.com/read/28018211/cistanche-tubulosa-protects-dopaminergic-neurons-through-regulation-of-apoptosis-and-glial-cell-derived-neurotrophic-factor-in-vivo-and-in-vitro
#17
Qian Xu, Wen Fan, Shui-Fen Ye, Yi-Bo Cong, Wei Qin, Shi-Ya Chen, Jing Cai
Parkinson's disease (PD) is a neurodegenerative disease with the pathological hallmark of reduced nigrostriatal dopamine. In traditional Chinese medicine (TCM) clinical practice, the nanopowder of Cistanche tubulosa has therapeutic effects on PD. To identify the therapeutic mechanism, this study tested the protective effect of different doses of MPP(+)-induced toxicity in MES23.5 cells using the MTT assay and in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice (vehicles). Immunohistochemistry was used to assess cytomorphology and tyrosine hydroxylase (TH) expression...
2016: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28017962/sirt1-plays-a-neuroprotective-role-in-traumatic-brain-injury-in-rats-via-inhibiting-the-p38-mapk-pathway
#18
Hong Yang, Zheng-Tao Gu, Li Li, Mac Maegele, Bi-Ying Zhou, Feng Li, Ming Zhao, Ke-Sen Zhao
Traumatic brain injury (TBI) is a major cause of disability and death in patients who experience a traumatic injury. Mitochondrial dysfunction is one of the main factors contributing to secondary injury in TBI-associated brain damage. Evidence of compromised mitochondrial function after TBI has been, but the molecular mechanisms underlying the pathogenesis of TBI are not well understood. Silent information regulator family protein 1 (SIRT1), a member of the NAD(+)-dependent protein deacetylases, has been shown to exhibit neuroprotective activities in animal models of various pathologies, including ischemic brain injury, subarachnoid hemorrhage and several neurodegenerative diseases...
December 26, 2016: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28017206/sevoflurane-pre-conditioning-increases-phosphorylation-of-erk1-2-and-ho-1-expression-via-inhibition-of-mptp-in-primary-rat-cortical-neurons-exposed-to-ogd-r
#19
Li-Min Zhang, Dong-Xue Zhang, Xiao-Chun Zhao, Wen-Bo Sun, Xiao-Jing Jiang
BACKGROUND: As an indispensable clinical inhalation anesthetic, sevoflurane is widely used for peri-operative sedation. The neuroprotective effect of sevoflurane pre-conditioning against cerebral ischemia/reperfusion has been gradually realized, but the underlying mechanism during the early reperfusion period has not been established. METHOD: Primary cultured cortical neurons were treated with 2% sevoflurane pre-conditioning for 30min, exposed to oxygen-glucose deprivation for 90min, and followed by 60min of reperfusion (OGD/R)...
January 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28006954/the-neuroprotective-effect-of-dimethyl-fumarate-in-a-mptp-mouse-model-of-parkinson-s-disease-involvement-of-reactive-oxygen-species-nuclear-factor-%C3%AE%C2%BAb-nuclear-transcription-factor-related-to-nf-e2
#20
Michela Campolo, Giovanna Casili, Flavia Biundo, Rosalia Crupi, Marika Cordaro, Salvatore Cuzzocrea, Emanuela Esposito
AIM: Oxidative stress plays a key role in Parkinson's disease (PD) and nuclear transcription factor related to NF-E2 (Nrf-2) is involved in neuroprotection against PD. The aim of the present study was to investigate the neurotherapeutic action, NF-κB/Nrf-2 dependent, of DMF in a mouse model of PD and in vitro SHSY-5Y cells. RESULTS: Daily oral gavage of DMF (10, 30 and 100 mg/kg) significantly reduced neuronal degeneration of dopaminergic tract and behavioral impairments induced by four injections of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)...
December 23, 2016: Antioxidants & Redox Signaling
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