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https://www.readbyqxmd.com/read/28631231/2-3-dideoxycytidine-protects-dopaminergic-neurons-in-a-mouse-model-of-parkinson-s-disease
#1
Jianyi Niu, Jing Xiong, Dan Hu, Fei Zeng, Shuke Nie, Shanping Mao, Tao Wang, Zhentao Zhang, Zhaohui Zhang
DNA polymerase-β (DNA pol-β) plays a crucial role in the pathogenesis of Parkinson's disease (PD). The aim of this study was to investigate the neuroprotective effects of a DNA polymerase-β inhibitor 2',3'-dideoxycytidine (DDC) in PD models. In the in vitro studies, primary cultured neurons were challenged with 1-methyl-4-phenylpyridinium ion (MPP(+)). The expression of DNA pol-β was assessed using western blot. The neuroprotective effect of DNA pol-β knockdown and DNA pol-β inhibitor DDC was determined using cell viability assay and caspase-3 activity assay...
June 19, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28630004/co-releasing-molecules-2-attenuates-ox-ldl-induced-injury-in-huvecs-by-ameliorating-mitochondrial-function-and-inhibiting-wnt-%C3%AE-catenin-pathway
#2
Hai-Jian Sun, Dong-Yan Xu, Yi-Xin Sun, Tong Xue, Chen-Xing Zhang, Zhi-Xuan Zhang, Wei Lin, Ke-Xue Li
Oxidized low-density lipoprotein (ox-LDL) is well known to disrupt normal functionality of endothelium, which plays a prominent role in endothelial dysfunction in many cardiovascular diseases. CO-releasing molecule 2 (CORM-2) is a promising candidate for treatment of cardiovascular diseases. However, it has not been defined whether CORM-2 might improve endothelial injury induced by ox-LDL. The present study was undertaken to determine the regulatory role of CORM-2 in cell injury of ox-LDL-treated human umbilical vein endothelial cells (HUVECs)...
June 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28625317/sphingosine-1-phosphate-postconditioning-protects-against-myocardial-ischemia-reperfusion-injury-in-rats-via-mitochondrial-signaling-and-akt-gsk3%C3%AE-phosphorylation
#3
Rui Fang, Lu-Lu Zhang, Li-Zhi Zhang, Wenchang Li, Mengmeng Li, Ke Wen
BACKGROUND AND AIMS: Although preconditioning of sphingosine 1-phosphate (S1P) has been shown to protect myocytes from hypoxia reoxgenation injury in vitro, the role of S1P postconditioning on myocardial ischemia reperfusion injury (MIRI) in vivo and its related mechanism are unknown. The aim of this study was to investigate the protective role of sphingosine 1-phosphate (S1P) postconditioning in MIRI via its effects on mitochondrial signaling and Akt/Gsk3β phosphorylation. METHODS: Rats were subjected to MIRI, consisting of 30 min of ischemia followed by 120 min of reperfusion, with S1P administered at the beginning of the reperfusion...
February 2017: Archives of Medical Research
https://www.readbyqxmd.com/read/28611598/early-paradoxical-increase-of-dopamine-a-neurochemical-study-of-olfactory-bulb-in-asymptomatic-and-symptomatic-mptp-treated-monkeys
#4
Christian Pifl, Harald Reither, Natalia Lopez-Gonzalez Del Rey, Carmen Cavada, Jose A Obeso, Javier Blesa
Parkinson's disease (PD) is a neurodegenerative disease with both motor and non-motor manifestations. Hyposmia is one of the early non-motor symptoms, which can precede motor symptoms by several years. The relationship between hyposmia and PD remains elusive. Olfactory bulb (OB) pathology shows an increased number of olfactory dopaminergic cells, protein aggregates and dysfunction of neurotransmitter systems. In this study we examined tissue levels of dopamine (DA) and serotonin (5-hydroxytryptamine, 5-HT) and their metabolites, of noradrenaline (NA) and of the amino acid neurotransmitters aspartate, glutamate, taurine and γ-aminobutyric acid in OBs of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treated Macaca fascicularis in different stages, including monkeys who were always asymptomatic, monkeys who recovered from mild parkinsonian signs, and monkeys with stable moderate or severe parkinsonism...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28611284/activation-of-the-atf2-creb-pgc-1%C3%AE-pathway-by-metformin-leads-to-dopaminergic-neuroprotection
#5
Hojin Kang, Rin Khang, Sangwoo Ham, Ga Ram Jeong, Hyojung Kim, Minkyung Jo, Byoung Dae Lee, Yun Il Lee, Areum Jo, Chi Hu Park, Hyein Kim, Jeongkon Seo, Sun Ha Paek, Yun-Song Lee, Jeong-Yun Choi, Yunjong Lee, Joo-Ho Shin
Progressive dopaminergic neurodegeneration is responsible for the canonical motor deficits in Parkinson's disease (PD). The widely prescribed anti-diabetic medicine metformin is effective in preventing neurodegeneration in animal models; however, despite the significant potential of metformin for treating PD, the therapeutic effects and molecular mechanisms underlying dopaminergic neuroprotection by metformin are largely unknown.In this study, we found that metformin induced substantial proteomic changes, especially in metabolic and mitochondrial pathways in the substantia nigra (SN)...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28601951/acupuncture-stimulation-at-gb34-suppresses-1-methyl-4-phenyl-1-2-3-6-tetrahydropyridine-induced-oxidative-stress-in-the-striatum-of-mice
#6
Yukyung Lee, Gaeun Choi, Hyongjun Jeon, Dongsoo Kim, Sun Ryu, Sungtae Koo, Ki-Tae Ha, Seungtae Kim
Recent studies have suggested that increased oxidative stress is a potential etiology in Parkinson's disease (PD). In this study, we investigated whether acupuncture regulates antioxidants in the striatum (ST) of a PD mouse model. Male C57BL/6 mice were administered 30 mg/kg of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intraperitoneally once a day for 5 days and given acupuncture stimulation at SI3 or GB34 (Yanglingquan) was for 12 consecutive days. Dopaminergic neuronal survival in the nigrostriatal pathway and DJ-1 expression in the ST was evaluated by immunostaining, and the activities of superoxide dismutase (SOD) and catalase (CAT) in the ST was by enzyme-linked immunosorbent assay...
June 10, 2017: Journal of Physiological Sciences: JPS
https://www.readbyqxmd.com/read/28595910/not-all-boronic-acids-with-a-five-membered-cycle-induce-tremor-neuronal-damage-and-decreased-dopamine
#7
Maribel Pérez-Rodríguez, Esperanza García-Mendoza, Eunice D Farfán-García, Bhaskar C Das, Fabiola J Ciprés-Flores, José G Trujillo-Ferrara, Feliciano Tamay-Cach, Marvin A Soriano-Ursúa
Several striatal toxins can be used to induce motor disruption. One example is MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), whose toxicity is accepted as a murine model of parkinsonism. Recently, 3-Thienylboronic acid (3TB) was found to produce motor disruption and biased neuronal damage to basal ganglia in mice. The aim of this study was to examine the toxic effects of four boronic acids with a close structural relationship to 3TB (all having a five-membered cycle), as well as boric acid and 3TB. These boron-containing compounds were compared to MPTP regarding brain access, morphological disruption of the CNS, and behavioral manifestations of such disruption...
June 6, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28592981/acupuncture-stimulation-at-gb34-restores-mptp-induced-neurogenesis-impairment-in-the-subventricular-zone-of-mice
#8
Hyongjun Jeon, Sun Ryu, Dongsoo Kim, Sungtae Koo, Ki-Tae Ha, Seungtae Kim
Adult neurogenesis has recently been considered a new therapeutic paradigm of Parkinson's disease. In this study, we investigated whether acupuncture restores 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- (MPTP-) induced impaired neurogenesis in the subventricular zone (SVZ). Male C57BL/6 mice were given 30 mg/kg of MPTP intraperitoneally once a day for 5 days, after which they were intraperitoneally injected with 50 mg/kg of bromodeoxyuridine (BrdU) and given acupuncture stimulation at HT7 or GB34 for 12 consecutive days...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28591721/ginkgolide-k-attenuates-neuronal-injury-after-ischemic-stroke-by-inhibiting-mitochondrial-fission-and-gsk-3%C3%AE-dependent-increases-in-mitochondrial-membrane-permeability
#9
Xu Zhou, Hui-Ying Wang, Bin Wu, Cai-Yi Cheng, Wei Xiao, Zhen-Zhong Wang, Yu-Yu Yang, Ping Li, Hua Yang
Ginkgolide K (GK) belongs to the ginkgolide family of natural compounds found in Ginkgo biloba leaves, which have been used for centuries to treat cerebrovascular and cardiovascular diseases. We evaluated the protective effects of GK against neuronal apoptosis by assessing its ability to sustain mitochondrial integrity and function. Co-immunoprecipitation showed that Drp1 binding to GSK-3β was increased after an oxygen-glucose deprivation/reperfusion (OGD/R) insult in cultured neuroblastoma cells. This induced Drp1 and GSK-3β translocation to mitochondria and mitochondrial dysfunction, which was attenuated by GK...
May 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28583715/novel-insights-into-the-antioxidant-role-of-tauroursodeoxycholic-acid-in-experimental-models-of-parkinson-s-disease
#10
Alexandra I Rosa, Inês Fonseca, Maria João Nunes, Sara Moreira, Elsa Rodrigues, Andreia Neves Carvalho, Cecília M P Rodrigues, Maria João Gama, Margarida Castro-Caldas
Impaired mitochondrial function and generation of reactive oxygen species are deeply implicated in Parkinson's disease progression. Indeed, mutations in genes that affect mitochondrial function account for most of the familial cases of the disease, and postmortem studies in sporadic PD patients brains revealed increased signs of oxidative stress. Moreover, exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a mitochondrial complex I inhibitor, leads to clinical symptoms similar to sporadic PD. The bile acid tauroursodeoxycholic acid (TUDCA) is an anti-apoptotic molecule shown to protect against MPTP-induced neurodegeneration in mice, but the mechanisms involved are still incompletely identified...
June 2, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28580188/on-the-relationship-between-energy-metabolism-proteostasis-aging-and-parkinson-s-disease-possible-causative-role-of-methylglyoxal-and-alleviative-potential-of-carnosine
#11
REVIEW
Alan R Hipkiss
Recent research shows that energy metabolism can strongly influence proteostasis and thereby affect onset of aging and related disease such as Parkinson's disease (PD). Changes in glycolytic and proteolytic activities (influenced by diet and development) are suggested to synergistically create a self-reinforcing deleterious cycle via enhanced formation of triose phosphates (dihydroxyacetone-phosphate and glyceraldehyde-3-phosphate) and their decomposition product methylglyoxal (MG). It is proposed that triose phosphates and/or MG contribute to the development of PD and its attendant pathophysiological symptoms...
May 2017: Aging and Disease
https://www.readbyqxmd.com/read/28579963/olesoxime-inhibits-cardioplegia-induced-ischemia-reperfusion-injury-a-study-in-langendorff-perfused-rabbit-hearts
#12
Aida Salameh, Maren Keller, Ingo Dähnert, Stefan Dhein
Objective: During cardioplegia, which is often used in cardiac surgery, the heart is subjected to global ischemia/reperfusion injury, which can result in a post-operative impairment of cardiac function. Mitochondria permeability transition pores (MPTP) play a key role in cardiomyocyte survival after ischemia/reperfusion injury. It was shown in clinical settings that blockers of MPTP like cyclosporine might have a positive influence on cardiac function after cardioplegic arrest. Olesoxime, which is a new drug with MPTP blocking activity, has been introduced as a neuroprotective therapeutic agent...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28579395/cryopreservation-maintains-functionality-of-human-ipsc-dopamine-neurons-and-rescues-parkinsonian-phenotypes-in%C3%A2-vivo
#13
Dustin R Wakeman, Benjamin M Hiller, David J Marmion, Christopher W McMahon, Grant T Corbett, Kile P Mangan, Junyi Ma, Lauren E Little, Zhong Xie, Tamara Perez-Rosello, Jaime N Guzman, D James Surmeier, Jeffrey H Kordower
A major challenge for clinical application of pluripotent stem cell therapy for Parkinson's disease (PD) is large-scale manufacturing and cryopreservation of neurons that can be efficiently prepared with minimal manipulation. To address this obstacle, midbrain dopamine neurons were derived from human induced pluripotent stem cells (iPSC-mDA) and cryopreserved in large production lots for biochemical and transplantation studies. Cryopreserved, post-mitotic iPSC-mDA neurons retained high viability with gene, protein, and electrophysiological signatures consistent with midbrain floor-plate lineage...
May 22, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28578987/chronic-cerebral-hypoperfusion-independently-exacerbate-cognitive-impairment-within-the-pathopoiesis-of-parkinson-s-disease-via-microvascular-pathology
#14
Hongmei Tang, Yuyuan Gao, Qingxi Zhang, Kun Nie, Ruiming Zhu, Liang Gao, Shujun Feng, Limin Wang, Jiehao Zhao, Zhiheng Huang, Yuhu Zhang, Lijuan Wang
To date, the role of microvascular pathology and CHH in the development of PD-MCI is unclear. Here we investigated how cognitive impairment could be exacerbated in a mouse model of combined injury through the interaction of chronic cerebral hypoperfusion(CHH) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP) toxicity damage. In the present study, C57BL/6 mouse underwent MPTP injection. Subjects were classified into PD with cognitive normal (PDCN) group and PD with mild cognitive impairment of (PD-MCI) group via Morris water maze test...
June 1, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28577132/tangeretin-inhibits-neurodegeneration-and-attenuates-inflammatory-responses-and-behavioural-deficits-in-1-methyl-4-phenyl-1-2-3-6-tetrahydropyridine-mptp-induced-parkinson-s-disease-dementia-in-rats
#15
Jin-Song Yang, Xiao-Hong Wu, Hao-Gang Yu, Li-Song Teng
Our aim was to investigate whether tangeretin, a citrus flavonoid, was able to prevent neuroinflammation and improve dementia in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced rodent model of Parkinson's disease (PD). MPTP-HCl was infused into the substantia nigra pars compacta of male Sprague-Dawley rats. Tangeretin (50, 100 or 200 mg/kg body weight) was administered orally starting 3 days prior to MPTP injection and was continued for 20 days following injection. MPTP-lesioned rats revealed motor dysfunction in bar test and rota rod tests...
June 2, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28576659/ceftriaxone-reverses-deficits-of-behavior-and-neurogenesis-in-an-mptp-induced-rat-model-of-parkinson-s-disease-dementia
#16
Ming-Hong Hsieh, Wan-Yun Meng, Wen-Chieh Liao, Jun-Cheng Weng, Hsin-Hua Li, Hong-Lin Su, Chih-Li Lin, Ching-Sui Hung, Ying-Jui Ho
Hyperactivity of the glutamatergic system is involved in excitotoxicity and neurodegeneration in Parkinson's disease (PD) so that glutamatergic modulation maybe a potential therapeutic target for PD. Ceftriaxone (CEF) has been reported to increase glutamate uptake by increasing glutamate transporter expression and has been demonstrated neuroprotective effects in animal study. The aim of this study was to determine the effects of CEF on behavior and neurogenesis in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD rat model...
May 30, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28572055/estrogen-regulates-spatially-distinct-cardiac-mitochondrial-subpopulations
#17
Rogério Faustino Ribeiro Junior, Paula Lopes Rodrigues, Elis Aguiar Morra, Karoline Sousa Ronconi, Patrícia Ribeiro Do Val Lima, Marcella Leite Porto, Maylla Ronacher Simões, Dalton Valentim Vassallo, Suely Gomes Figueiredo, Ivanita Stefanon
Increased susceptibility to permeability transition pore (mPTP) is a significant concern to decreased cardiac performance in postmenopausal females. The goal of this study was to assess the effects of estrogen deficiency on the two spatially distinct mitochondrial subpopulations from left ventricle: subsarcolemmal mitochondria (SSM) and intermyofibrillar mitochondria (IFM) based on: morphology, membrane potential, oxidative phosphorylation, mPTP and reactive oxygen species production. Female rats (8weeks old) that underwent bilateral ovariectomy were randomly assigned to receive daily treatment with placebo (OVX), estrogen replacement (OVX+E2) and Sham for 60days...
May 29, 2017: Mitochondrion
https://www.readbyqxmd.com/read/28560396/mitochondrial-ca2-removal-amplifies-trail-cytotoxicity-toward-apoptosis-resistant-tumor-cells-via-promotion-of-multiple-cell-death-modalities
#18
Natsuhiko Takata, Yohei Ohshima, Miki Suzuki-Karasaki, Yukihiro Yoshida, Yasuaki Tokuhashi, Yoshihiro Suzuki-Karasaki
Ca2+ has emerged as a new target for cancer treatment since tumor-specific traits in Ca2+ dynamics contributes to tumorigenesis, malignant phenotypes, drug resistance, and survival in different tumor types. However, Ca2+ has a dual (pro-death and pro-survival) function in tumor cells depending on the experimental conditions. Therefore, it is necessary to minimize the onset of the pro-survival Ca2+ signals caused by the therapy. For this purpose, a better understanding of pro-survival Ca2+ pathways in cancer cells is critical...
May 25, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28560002/prostaglandin-e1-protects-coronary-microvascular-function-via-the-glycogen-synthase-kinase-3%C3%AE-mitochondrial-permeability-transition-pore-pathway-in-rat-hearts-subjected-to-sodium-laurate-induced-coronary-microembolization
#19
Houyong Zhu, Yu Ding, Xiaoqun Xu, Meiya Li, Yangliang Fang, Beibei Gao, Hengyi Mao, Guoxin Tong, Liang Zhou, Jinyu Huang
Prostaglandin E1 (PGE1) is used as a pretreatment for ischemia reperfusion injury in many biological systems. However, its value as a pretreatment for coronary microembolization (CME) is unknown. The goal of this study was to determine whether PGE1 would protect against CME. In a CME rat model, we observed microthrombi and early myocardial ischemia, with endothelium appearing exfoliated and mitochondria having irregular morphology and decreased internal complexity. The level of fibrinogen-like protein 2 prothrombinase was increased and superoxide dismutase and catalase levels were decreased...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28559847/high-sensitivity-of-sirt3-deficient-hearts-to-ischemia-reperfusion-is-associated-with-mitochondrial-abnormalities
#20
Rebecca M Parodi-Rullán, Xavier Chapa-Dubocq, Pedro J Rullán, Sehwan Jang, Sabzali Javadov
Aim: Sirtuins are NAD(+)-dependent deacetylases that regulate cell metabolism through protein acetylation/deacetylation, and SIRT3 is the major deacetylase among mitochondrial isoforms. Here, we elucidated the possible role of acetylation of cyclophilin D, a key regulator of the mitochondrial permeability transition pore (mPTP), in mitochondria-mediated cardiac dysfunction induced by ischemia-reperfusion (IR) in wild type (WT) and SIRT3 knockout (SIRT3(-/-)) mice. Materials and Methods: Isolated and Langendorff-mode perfused hearts of WT and SIRT3(-/-) mice were subjected to 25-min global ischemia followed by 60-min of reperfusion in the presence or absence of the mPTP inhibitor, sanglifehrin A (SfA)...
2017: Frontiers in Pharmacology
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