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https://www.readbyqxmd.com/read/28224704/advanced-glycation-end-products-regulate-anabolic-and-catabolic-activities-via-nlrp3-inflammasome-activation-in-human-nucleus-pulposus-cells
#1
Yu Song, Yan Wang, Yukun Zhang, Wen Geng, Wei Liu, Yong Gao, Shuai Li, Kun Wang, Xinghuo Wu, Liang Kang, Cao Yang
Intervertebral disc degeneration is widely recognized as a cause of lower back pain, neurological dysfunction and other musculoskeletal disorders. The major inflammatory cytokine IL-1β is associated with intervertebral disc degeneration; however, the molecular mechanisms that drive IL-1β production in the intervertebral disc, especially in nucleus pulposus (NP) cells, are unknown. In some tissues, advanced glycation end products (AGEs), which accumulate in NP tissues and promote its degeneration, increase oxidative stress and IL-1β secretion, resulting in disorders, such as obesity, diabetes mellitus and ageing...
February 22, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28224174/spectroscopic-polarographic-and-microcalorimetric-studies-on-mitochondrial-dysfunction-induced-by-ethanol
#2
Long Ma, Jia-Xin Dong, Can Wu, Xue-Yi Li, Jing Chen, Hong Zhang, Yi Liu
Liver mitochondria are involved in several important life processes; mitochondrial dysfunction and disorders are implicated in several human diseases. Alcohol permeates all tissues of the body and exerts some intrinsic hepatotoxicity. In this work, our results demonstrated that ethanol caused a series of mitochondria permeability transition pore (MPTP) opening factors such as mitochondrial swelling, increased permeability of H(+) and K(+), collapsed membrane potential, and increased membrane fluidity. Furthermore, mitochondrial ultrastructure alternation observed clearly by transmission electron microscopy and the release of Cytochrome c could explain the MPTP opening from another aspect...
February 21, 2017: Journal of Membrane Biology
https://www.readbyqxmd.com/read/28223210/a-novel-glp-1-gip-dual-receptor-agonist-protects-from-6-ohda-lesion-in-a-rat-model-of-parkinson-s-disease
#3
Jaishree Jalewa, Mohit Kumar Sharma, Simon Gengler, Christian Hölscher
The incretins glucagon-like peptide 1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP) are growth factors that have shown neuroprotective effects in animal models of Parkinson's and Alzheimer's disease. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in a clinical trial in Parkinson's disease (PD) patients. GLP-1 analogues are currently on the market as treatments for type II diabetes. We previously showed that the novel dual agonist (DA-JC1) was effective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD...
February 18, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28219749/behavioral-phenotypes-associated-with-mptp-induction-of-partial-lesions-in-common-marmosets-callithrix-jacchus
#4
Kimberley A Phillips, Corinna N Ross, Jennifer Spross, Catherine J Cheng, Alyssa Izquierdo, K C Biju, Cang Chen, Senlin Li, Suzette D Tardif
Parkinson's disease is a chronic neurodegenerative disorder with the core motor features of resting tremor, bradykinesia, rigidity, and postural instability. Non-motor symptoms also occur, and include cognitive dysfunction, mood disorders, anosmia (loss of smell), and REM sleep disturbances. As the development of medications and other therapies for treatment of non-motor symptoms is ongoing, it is essential to have animal models that aid in understanding the neural changes underlying non-motor PD symptoms and serve as a testing ground for potential therapeutics...
February 17, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28197936/salvianolic-acid-a-protects-neonatal-cardiomyocytes-against-hypoxia-reoxygenation-induced-injury-by-preserving-mitochondrial-function-and-activating-akt-gsk-3%C3%AE-signals
#5
Xue-Li Li, Ji-Ping Fan, Jian-Xun Liu, Li-Na Liang
OBJECTIVE: To investigate the effects of salvianolic acid A (SAA) on cardiomyocyte apoptosis and mitochondrial dysfunction in response to hypoxia/reoxygenation (H/R) injury and to determine whether the Akt signaling pathway might play a role. METHODS: An in vitro model of H/R injury was used to study outcomes on primary cultured neonatal rat cardiomyocytes. The cardiomyocytes were treated with 12.5, 25, 50 μg/mL SAA at the beginning of hypoxia and reoxygenation, respectively...
February 15, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28197079/sirt3-in-neural-stem-cells-attenuates-microglia-activation-induced-oxidative-stress-injury-through-mitochondrial-pathway
#6
De-Qi Jiang, Yan Wang, Ming-Xing Li, Yan-Jiao Ma, Yong Wang
Sirtuin 3 (SIRT3), a mitochondrial protein, is involved in energy metabolism, cell apoptosis and mitochondrial function. However, the role of SIRT3 in neural stem cells (NSCs) remains unknown. In previous studies, we found that microglia activation-induced cytotoxicity negatively regulated survival of NSCs, along with mitochondrial dysfunction. The aim of this study was to investigate the potential neuroprotective effects of SIRT3 on the microglia activation-induced oxidative stress injury in NSCs and its possible mechanisms...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28196514/defining-the-contribution-of-neuroinflammation-to-parkinson-s-disease-in-humanized-immune-system-mice
#7
Gunjan Dhawan Manocha, Angela Marie Floden, Kendra Lynn Puig, Kumi Nagamoto-Combs, Clemens R Scherzer, Colin Kelly Combs
BACKGROUND: Reactive microglia have been associated with the histological changes that occur in Parkinson's disease brains and mouse models of the disease. Multiple studies from autopsy brains have verified the presence of microgliosis in several brain regions including substantia nigra, striatum, hippocampus and various cortical areas. MPTP injections in rodents have also shown striato-nigral microgliosis correlating with the loss of dopaminergic neurons. However, consistent data with respect to cytokine and immune cell changes during Parkinson's disease have not been fully defined...
February 14, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28194639/ultrafine-particulate-matter-increases-cardiac-ischemia-reperfusion-injury-via-mitochondrial-permeability-transition-pore
#8
Nathan A Holland, Chad R Fraiser, Ruben C Sloan, Robert B Devlin, David A Brown, Christopher J Wingard
Ultrafine particulate matter (UFP) has been associated with increased cardiovascular morbidity and mortality. However, the mechanisms that drive PM-associated cardiovascular disease and dysfunction remain unclear. We examined the impact of oropharyngeal aspiration of 100 μg UFP from the Chapel Hill, NC, air shed in Sprague-Dawley rats on cardiac function, arrhythmogenesis, and cardiac ischemia/reperfusion (I/R) injury using a Langendorff working heart model. We found that exposure to UFP was capable of significantly exacerbating cardiac I/R injury without changing overall cardiac function or major changes in arrhythmogenesis...
February 13, 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/28192111/effects-of-progesterone-administered-after-mptp-on-dopaminergic-neurons-of-male-mice
#9
Nadhir Litim, Marc Morissette, Thérèse Di Paolo
Progesterone neuroprotection of striatal dopamine (DA) in male mice lesioned with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was previously reported when administered before MPTP or an hour after. A dose of MPTP to induce a partial lesion was used to model early stages or prodromal Parkinson. We hypothesized that brain DA can be restored by progesterone administered early (24 h) or later (5 days) after MPTP. Male mice received 4 injections of MPTP (8 mg/kg) and progesterone (8 mg/kg) once daily for 5 days started 24 h or 5 days after MPTP...
February 10, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28191472/suppression-of-excessive-histone-deacetylases-activity-in-diabetic-hearts-attenuates-myocardial-ischemia-reperfusion-injury-via-mitochondria-apoptosis-pathway
#10
Yang Wu, Yan Leng, Qingtao Meng, Rui Xue, Bo Zhao, Liying Zhan, Zhongyuan Xia
Background. Histone deacetylases (HDACs) play a pivotal role in signaling modification and gene transcriptional regulation that are essential for cardiovascular pathophysiology. Diabetic hearts with higher HDACs activity were more vulnerable to myocardial ischemia/reperfusion (MI/R) injury compared with nondiabetic hearts. We are curious about whether suppression of excessive HDACs activity in diabetic heart protects against MI/R injury. Methods. Diabetic rats were subjected to 45 min of ischemia, followed by 3 h of reperfusion...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28190476/neuroprotective-properties-of-icariin-in-mptp-induced-mouse-model-of-parkinson-s-disease-involvement-of-pi3k-akt-and-mek-erk-signaling-pathways
#11
Wen-Fang Chen, Lin Wu, Zhong-Rui Du, Lei Chen, Ai-Li Xu, Xiao-Han Chen, Ji-Jun Teng, Man-Sau Wong
BACKGROUND: Epimedium sagittatum is a traditional Chinese herb normally which is used to treat the osteoporosis, cardiovascular dysfunction, and to improve neurological and sexual function in China, Korea and Japan. Icariin is the major active ingredient in Epimedium sagittatum. In the present research, we examined the neuroprotective effects of icariin on dopaminergic neurons and the possible mechanisms in a mouse model of Parkinson's disease (PD). METHODS: Ovariectomized PD mice were treated with vehicle or icariin (3 days before MPTP injections) with or without the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 or mitogen-activated protein kinase kinase (MEK) inhibitor PD98059...
February 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28190394/neuroprotective-effect-of-atremorine-in-an-experimental-model-of-parkinson%C3%A2-s-disease
#12
Ivan Carrera, Lucia Fernandez-Novoa, Carolina Sampedro, Ramon Cacabelos
Parkinsonian-like state was generated in mice by the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to study the effects of Atremorine in Parkinson's disease (PD) related neuropathology and behavior deficits. This devastating disease is caused by the progressive degeneration of dopaminergic neurons in the substantia nigra. Numerous therapeutic strategies have been developed to protect neuronal damage, although no effective treatment for PD has been validated yet. This study tested the preventive and therapeutic neuroprotective effect of Atremorine on MPTP parkinsonian mouse model...
February 10, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28187451/gsk1059615-kills-head-and-neck-squamous-cell-carcinoma-cells-possibly-via-activating-mitochondrial-programmed-necrosis-pathway
#13
Jing Xie, Quan Li, Xi Ding, Yunyun Gao
This study tested the anti-head and neck squamous cell carcinoma (HNSCC) cell activity by GSK1059615, a novel PI3K and mTOR dual inhibitor. GSK1059615 inhibited survival and proliferation of established (SCC-9, SQ20B and A253 lines) and primary human HNSCC cells. GSK1059615 blocked PI3K-AKT-mTOR activation in HNSCC cells. Intriguingly, GSK1059615 treatment in HNSCC cells failed to provoke apoptosis, but induced programmed necrosis. The latter was tested by mitochondria depolarization, ANT-1-cyclophilin-D mitochondrial association and lactate dehydrogenase (LDH) release...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28186490/atomistic-simulations-indicate-the-c-subunit-ring-of-the-f1fo-atp-synthase-is-not-the-mitochondrial-permeability-transition-pore
#14
Wenchang Zhou, Fabrizio Marinelli, Corrine Nief, José D Faraldo-Gómez
Pathological metabolic conditions such as ischemia induce the rupture of the mitochondrial envelope and the release of pro-apoptotic proteins, leading to cell death. At the onset of this process, the inner mitochondrial membrane becomes depolarized and permeable to osmolytes, due to the opening of a non-selective protein channel of unknown molecular identity. A recent study purports that this channel, referred to as Mitochondrial Permeability Transition Pore (MPTP), is the lumen of the c-subunit ring of the ATP synthase, upon dissociation from the catalytic domain...
February 10, 2017: ELife
https://www.readbyqxmd.com/read/28185878/chronic-mild-stress-augments-mptp-induced-neurotoxicity-in-a-murine-model-of-parkinson-s-disease
#15
Udaiyappan Janakiraman, Thamilarasan Manivasagam, Arokiasamy Justin Thenmozhi, Chinnasamy Dhanalakshmi, Musthafa Mohamed Essa, Byoung-Joon Song, Gilles J Guillemin
Depression is frequently encountered during Parkinson's disease (PD) as a non-motor feature, which has been reported to cause and exaggerate motor deficits and neurodegenerative events in experimental PD models. We studied the effect of chronic mild stress (CMS) (pre, post and pre & post) exposure mediated depression on motor and non-motor symptoms, oxidative stress, inflammation and brain derived neurotrophic factor (BDNF) levels and its related signalling molecules against the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/p) induced neurotoxicity in mice...
February 6, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28185818/amentoflavone-protects-dopaminergic-neurons-in-mptp-induced-parkinson-s-disease-model-mice-through-pi3k-akt-and-erk-signaling-pathways
#16
Qin Cao, Liyue Qin, Fei Huang, Xiaoshuang Wang, Liu Yang, Hailian Shi, Hui Wu, Beibei Zhang, Ziyu Chen, Xiaojun Wu
Parkinson's disease (PD) is characterized by the progressive degeneration of dopaminergic neurons in substantia nigra pars compacta (SNpc). Mitochondrial dysfunction and cell apoptosis are suggested to be actively involved in the pathogenesis of PD. In the present study, the neuroprotective effect of amentoflavone (AF), a naturally occurring biflavonoid from Selaginella tamariscina, was examined in PD models both in vitro and in vivo. On SH-SY5Y cells, AF treatment dose-dependently reduced 1-methyl-4-phenylpyridinium (MPP(+))-induced nuclear condensation and loss of cell viability without obvious cytotoxicity...
February 6, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28182002/rapamycin-upregulates-glutamate-transporter-and-il-6-expression-in-astrocytes-in-a-mouse-model-of-parkinson-s-disease
#17
Yunlong Zhang, Xiaoliang He, Xiaojuan Wu, Ming Lei, Zhiyun Wei, Xiuping Zhang, Lei Wen, Pingyi Xu, Shaomin Li, Shaogang Qu
Rapamycin protects mice against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced loss of dopaminergic neurons, which is an established model for Parkinson's disease. We demonstrated that rapamycin preserves astrocytic expression of glutamate transporters and glutamate reuptake. The protective effect was also observed in astrocyte cultures, indicating that rapamycin acts directly on astrocytes. In the MPTP model, rapamycin caused reduced expression of the E3 ubiquitin ligase Nedd4-2 (neuronal precursor cell expressed developmentally downregulated 4-2) and reduced colocalization of glutamate transporters with ubiquitin...
February 9, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28181692/irisin-plays-a-pivotal-role-to-protect-the-heart-against-ischemia-and-reperfusion-injury
#18
Hao Wang, Yu Tina Zhao, Shouyan Zhang, Patrycja M Dubielecka, Jianfeng Du, Naohiro Yano, Y Eugene Chin, Shougang Zhuang, Gangjian Qin, Ting C Zhao
Irisin, a newly identified hormone, is critical to modulating body metabolism, thermogenesis and reducing oxidative stresses. However, whether irisin protects the heart against myocardial ischemia and reperfusion (I/R) injury remains unknown. In this study, we determine the effect of irisin on myocardial I/R injury in the Langendorff perfused heart and cultured myocytes. Adult C57/BL6 mice were treated with irisin (100mg/kg) or vehicle for 30 minutes to elicit preconditioning. The isolated hearts were subjected to 30 min ischemia followed by 30 min reperfusion...
February 9, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28181071/neurotrophic-effect-of-asiatic-acid-a-triterpene-of-centella-asiatica-against-chronic-1-methyl-4-phenyl-1-2-3-6-tetrahydropyridine-hydrochloride-probenecid-mouse-model-of-parkinson-s-disease-the-role-of-mapk-pi3k-akt-gsk3%C3%AE-and-mtor-signalling-pathways
#19
Jagatheesan Nataraj, Thamilarasan Manivasagam, Arokiasamy Justin Thenmozhi, Musthafa Mohamed Essa
Regulation of various signalling (Ras-MAPK, PI3K and AKT) pathways by augmented activity of neurotrophic factors (NTFs) could prevent or halt the progress of dopaminergic loss in Parkinson's disease (PD). Various in vitro and in vivo experimental studies indicated anti-parkinsonic potential of asiatic acid (AA), a pentacyclic triterpene obtained from Centella asiatica. So the present study is designed to determine the neurotrophic effect of AA against 1-methyl 4-phenyl 1, 2, 3, 6-tetrahydropyridine hydrochloride/probenecid (MPTP/p) neurotoxicity in mice model of PD...
February 8, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28179991/a-homolog-of-cyclophilin-d-is-expressed-in-trypanosoma-cruzi-and-is-involved-in-the-oxidative-stress-damage-response
#20
Patricia L Bustos, Bibiana J Volta, Alina E Perrone, Natalia Milduberger, Jacqueline Bua
Mitochondria have an important role in energy production, homeostasis and cell death. The opening of the mitochondrial permeability transition pore (mPTP) is considered one of the key events in apoptosis and necrosis, modulated by cyclophilin D (CyPD), a crucial component of this protein complex. In Trypanosoma cruzi, the protozoan parasite that causes Chagas disease, we have previously described that mitochondrial permeability transition occurs after oxidative stress induction in a cyclosporin A-dependent manner, a well-known cyclophilin inhibitor...
2017: Cell Death Discovery
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