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https://www.readbyqxmd.com/read/27913104/d-ala2-gip-glu-pal-is-neuroprotective-in-a-chronic-parkinson-s-disease-mouse-model-and-increases-bndf-expression-while-reducing-neuroinflammation-and-lipid-peroxidation
#1
Yanwei Li, WeiZhen Liu, Lin Li, Christian Hölscher
Type 2 diabetes mellitus (T2DM) is a risk factor for Parkinson's disease (PD). Therefore, treatment to improve insulin resistance in T2DM may be useful for PD patients. Glucose dependent insulinotropic polypeptide (GIP) is a member of the incretin hormone family that can promote insulin release and improve insulin resistance. Several GIP analogues have been developed as potential treatments for T2DM. We had shown previously that D-Ala2-GIP-glu-PAL, a novel long-acting GIP analogue, can play a neuroprotective role in the PD mouse model induced by acute MPTP injection...
November 29, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27907091/real-time-fluorescence-measurements-of-ros-and-ca2-in-ischemic-reperfused-rat-hearts-detectable-increases-occur-only-after-mitochondrial-pore-opening-and-are-attenuated-by-ischemic-preconditioning
#2
Tatyana Andrienko, Philippe Pasdois, Andreas Rossbach, Andrew P Halestrap
Mitochondrial permeability transition pore (mPTP) opening is critical for ischemia / reperfusion (I/R) injury and is associated with increased [Ca2+] and reactive oxygen species (ROS). Here we employ surface fluorescence to establish the temporal sequence of these events in beating perfused hearts subject to global I/R. A bespoke fluorimeter was used to synchronously monitor surface fluorescence and reflectance of Langendorff-perfused rat hearts at multiple wavelengths, with simultaneous measurements of hemodynamic function...
2016: PloS One
https://www.readbyqxmd.com/read/27904701/sirt6-suppresses-mitochondrial-defects-and-cell-death-via-the-nf-%C3%AE%C2%BAb-pathway-in-myocardial-hypoxia-reoxygenation-induced-injury
#3
Ming-Yue Cheng, You-Wei Cheng, Jun Yan, Xiao-Qin Hu, Hui Zhang, Zhi-Rong Wang, Qin Yin, Wei Cheng
The present study explored changes of the SIRT6/NF-κB pathway in myocardial hypoxia/reoxygenation induced injury and the effects on mitochondrial damage and myocardial damage by regulating SIRT6. SIRT6 expression decreased and NF-κB expression increased in H9c2 cells during hypoxic injury. Cell death and mitochondrial defects paralleled mPTP opening, and a decrease in ΔΨm occurred in hypoxic myocytes compared with normoxic control cells in annexin V and propidium iodide staining and TUNEL results. These effects were suppressed in cells overexpressing SIRT6, but reemerged in cells expressing the SIRT6 mutant...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27904664/tauroursodeoxycholic-acid-inhibits-endoplasmic-reticulum-stress-blocks-mitochondrial-permeability-transition-pore-opening-and-suppresses-reperfusion-injury-through-gsk-3%C3%A3-in-cardiac-h9c2-cells
#4
Yuxi Xie, Yonggui He, Zhiliang Cai, Jianhang Cai, Mengyao Xi, Yidong Zhang, Jinkun Xi
This study investigates whether inhibition of endoplasmic reticulum (ER) stress prevents opening of the mitochondrial permeability transition pore (mPTP) and evaluates the corresponding signaling pathways involved in this process. Exposure of cardiac H9c2 cells to 800 µM H2O2 for 20 min opened mPTP in response to oxidative stress, as demonstrated by quenching of tetramethylrhodamine ethyl ester (TMRE) fluorescence. Oxidative stress-induced mPTP opening was rescued by the ER stress inhibitor tauroursodeoxycholic acid (TUDCA) in a dose-dependent manner at low concentrations...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27899315/injury-stimulated-sonic-hedgehog-expression-in-microglia-contributes-to-neuroinflammatory-response-in-the-mptp-model-of-parkinson-s-disease
#5
Jung Hwi Lee, Young Cheul Chung, Eugene Bok, Hankyu Lee, Sue Hee Huh, Ji Eun Lee, Byung Kwan Jin, Hyuk Wan Ko
Parkinson's disease (PD) is a progressive neurodegenerative disorder in which dopamine (DA) neurons in the substantia nigra pars compacta (SNpc) region are selectively destroyed. Sonic hedgehog (Shh) has been well known to play a key role in a variety of processes such as embryogenesis, cell proliferation and protection, and tissue repair during inflammation. However, the evidences for the innate role of Shh in adult brain injury are presently lacking and studies have been needed to unveil the importance of Shh in the process of neurodegeneration...
November 26, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27890431/neuroprotective-mechanisms-of-plant-extracts-against-mptp-induced-neurotoxicity-future-applications-in-parkinson-s-disease
#6
REVIEW
Abdelrahman Ibrahim Abushouk, Ahmed Negida, Hussien Ahmed, Mohamed M Abdel-Daim
Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease, affecting about seven to 10 million patients worldwide. The major pathological features of PD are loss of dopaminergic neurons in the nigrostriatal pathway and accumulation of alpha-synuclein molecules, forming Lewy bodies. Until now, there is no effective cure for PD, and investigators are searching for neuroprotective strategies to stop or slow the disease progression. The MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) induced neurotoxicity of the nigrostriatal pathway has been used to initiate PD in animal models...
November 24, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27889907/activation-of-nur77-in-microglia-attenuates-proinflammatory-mediators-production-and-protects-dopaminergic-neurons-from-inflammation-induced-cell-death
#7
Tian-Ya Liu, Xiao-Ying Yang, Long-Tai Zheng, Guang-Hui Wang, Xue-Chu Zhen
Microglia-mediated neuroinflammation plays a critical role in the pathological development of Parkinson's disease (PD). Orphan nuclear receptor Nur77 (Nur77) is abundant in neurons, while its role in microglia-mediated neuroinflammation remains unclear. The present data demonstrated that the expression of Nur77 in microglia was reduced accompanied with microglia activation in response to lipopolysaccharide (LPS) in vitro and in experimental MPTP-PD mouse model. Nur77 overexpression or application of Nur77 agonist CsnB suppressed the expression of proinflammatory genes, such as iNOS, COX-2, IL-1β, and TNF-α in the activated microglia, while silenced Nur77 exaggerated the inflammatory responses in microglia...
November 27, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27886240/identification-of-er-000444793-a-cyclophilin-d-independent-inhibitor-of-mitochondrial-permeability-transition-using-a-high-throughput-screen-in-cryopreserved-mitochondria
#8
Thomas Briston, Sian Lewis, Mumta Koglin, Kavita Mistry, Yongchun Shen, Naomi Hartopp, Ryosuke Katsumata, Hironori Fukumoto, Michael R Duchen, Gyorgy Szabadkai, James M Staddon, Malcolm Roberts, Ben Powney
Growing evidence suggests persistent mitochondrial permeability transition pore (mPTP) opening is a key pathophysiological event in cell death underlying a variety of diseases. While it has long been clear the mPTP is a druggable target, current agents are limited by off-target effects and low therapeutic efficacy. Therefore identification and development of novel inhibitors is necessary. To rapidly screen large compound libraries for novel mPTP modulators, a method was exploited to cryopreserve large batches of functionally active mitochondria from cells and tissues...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27882077/potential-protective-effects-of-autophagy-activated-in-mpp-treated-astrocytes
#9
Cunzhou Shen, Wenbiao Xian, Hongyan Zhou, Ling Chen, Zhong Pei
Astrocytes, which have various important functions, have previously been associated with Parkinsons disease (PD), particularly in 1-methyl-4-phenylpyridinium (MPP+) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) models of PD. MPP+ is the toxic metabolite of MPTP and is generated by the enzymatic activity of monoamine oxidase B, which is predominantly located in astrocytes. MPP+ acts as a mitochondrial complex I inhibitor. Autophagy is an evolutionarily conserved self-digestion pathway in eukaryotic cells, which occurs in response to various types of stress, including starvation and oxidative stress...
November 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27875543/irisin-ameliorates-hypoxia-reoxygenation-induced-injury-through-modulation-of-histone-deacetylase-4
#10
Yu Tina Zhao, Hao Wang, Shouyan Zhang, Jianfeng Du, Shougang Zhuang, Ting C Zhao
Irisin is a recently identified myokine which brings increases in energy expenditure and contributes to the beneficial effects of exercise through the browning of white adipose tissues. However, its effects in the heart remains unknown. This study sought to determine the effects of irisin on hypoxia/reoxygenation injury and its relationship with HDAC4. Wild type and stable HDAC4-overexpression cells were generated from H9c2 cardiomyoblasts. HDAC4 overexpression cells and wild type H9c2 cells were exposed to 24 hours of hypoxia followed by one hour of reoxygenation in vitro in the presence or absence of irisin (5 ng/ml)...
2016: PloS One
https://www.readbyqxmd.com/read/27874067/5-htr3-and-5-htr4-located-on-the-mitochondrial-membrane-and-functionally-regulated-mitochondrial-functions
#11
Qingyi Wang, Huiyuan Zhang, Hao Xu, Dongqing Guo, Hui Shi, Yuan Li, Weiwei Zhang, Yuchun Gu
5-HT has been reported to possess significant effects on cardiac activities, but activation of 5-HTR on the cell membrane failed to illustrate the controversial cardiac reaction. Because 5-HT constantly comes across the cell membrane via 5-HT transporter (5-HTT) into the cytoplasm, whether 5-HTR is functional present on the cellular organelles is unknown. Here we show 5-HTR3 and 5-HTR4 were located in cardiac mitochondria, and regulated mitochondrial activities and cellular functions. Knock down 5-HTR3 and 5-HTR4 in neonatal cardiomyocytes resulted in significant increase of cell damage in response to hypoxia, and also led to alternation in heart beating...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27871905/the-behavioural-and-neuroprotective-outcomes-when-670nm-and-810nm-near-infrared-light-are-applied-together-in-mptp-treated-mice
#12
Florian Reinhart, Nabil El Massri, Napoleon Torres, Claude Chabrol, Jenny Molet, Daniel M Johnstone, Jonathan Stone, Alim-Louis Benabid, John Mitrofanis, Cécile Moro
We have shown previously that when applied separately, 670nm and 810nm near infrared light (NIr) reduces behavioural deficits and offers neuroprotection in a MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model of Parkinson's disease. Here, we explored the beneficial outcomes when these NIr wavelengths were applied both together, either concurrently (at the same time) or sequentially (one after the other). Mice received MPTP injections (total of 50mg/kg) and had extracranial application of 670nm and/or 810nm NIr...
November 18, 2016: Neuroscience Research
https://www.readbyqxmd.com/read/27870937/spinosad-induces-programmed-cell-death-involves-mitochondrial-dysfunction-and-cytochrome-c-release-in-spodoptera-frugiperda-sf9-cells
#13
Mingjun Yang, Bo Wang, Jufang Gao, Yang Zhang, Wenping Xu, Liming Tao
Spinosad, a reduced-risk insecticide, acts on the nicotinic acetylcholine receptors and the gamma-aminobutyric acid receptor in the nervous system of target insects. However, its mechanism of action in non-neural insect cells is unclear. This study aimed to evaluate mitochondrial functional changes associated with spinosad in Spodoptera frugiperda (Sf9) insect cells. Our results indicate that in Sf9 cells, spinosad induces programmed cell death and mitochondrial dysfunction through enhanced reactive oxygen species production, mitochondrial permeability transition pore (mPTP) opening, and mitochondrial membrane potential collapse, eventually leading to cytochrome C release and apoptosis...
November 18, 2016: Chemosphere
https://www.readbyqxmd.com/read/27861892/the-regulator-of-calcineurin-1-increases-adenine-nucleotide-translocator-1-and-leads-to-mitochondrial-dysfunctions
#14
Hui Jiang, Chen Zhang, Yu Tang, Juan Zhao, Tan Wang, Heng Liu, Xiulian Sun
The overexpression of regulator of calcineurin 1 isoform 1 (RCAN1.1) has been implicated in mitochondrial dysfunctions of Alzheimer's disease (AD); however, the mechanism linking RCAN1.1 overexpression and the mitochondrial dysfunctions remains unknown. In this study, we use human neuroblastoma SH-SY5Y cells stably expressing RCAN1.1S and rat primary neurons infected with RCAN1.1S expression lentivirus to study the association of RCAN1 with mitochondrial functions. Our study here showed that the overexpression of RCAN1...
November 15, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27855359/discovery-of-benzimidazole-derivatives-as-modulators-of-mitochondrial-function-a-potential-treatment-for-alzheimer-s-disease
#15
TaeHun Kim, Ha Yun Yang, Beoung Gun Park, Seo Yun Jung, Jong-Hyun Park, Ki Duk Park, Sun-Joon Min, Jinsung Tae, Hyejin Yang, Suengmok Cho, Sung Jin Cho, Hyundong Song, Inhee Mook-Jung, Jiyoun Lee, Ae Nim Pae
In this study, we designed a library of compounds based on the structures of well-known ligands of the 18 kDa translocator protein (TSPO), one of the putative components of the mPTP. We performed diverse mitochondrial functional assays to assess their ability to restore cells from Aβ-induced toxicity in vitro and in vivo. Among tested compounds, compound 25 effectively improved cognitive function in animal models of AD. Given the excellent in vitro and in vivo activity and a favorable pharmacokinetic profile of compound 25, we believe that it can serve as a promising lead compound for a potential treatment option for AD...
November 9, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27847332/intralipid-protects-the-heart-in-late-pregnancy-against-ischemia-reperfusion-injury-via-caveolin2-stat3-gsk-3%C3%AE-pathway
#16
Jingyuan Li, Gregoire Ruffenach, Georgios Kararigas, Christine M Cunningham, Negar Motayagheni, Neusha Barakai, Soban Umar, Vera Regitz-Zagrosek, Mansoureh Eghbali
BACKGROUND: We recently demonstrated that the heart of late pregnant (LP) rodents is more prone to ischemia/reperfusion (I/R) injury compared to non-pregnant rodents. Lipids, particularly polyunsaturated fatty acids, have received special attention in the field of cardiovascular research. Here, we explored whether Intralipid (ITLD) protects the heart against I/R injury in LP rodents and investigated the mechanisms underlying this protection. METHODS AND RESULTS: In-vivo female LP rat hearts or ex-vivo isolated Langendorff-perfused LP mouse hearts were subjected to ischemia followed by reperfusion with PBS or ITLD (one bolus of 5mg/kg of 20% in in-vivo and 1% in ex-vivo)...
November 12, 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/27844285/th17-cells-induce-dopaminergic-neuronal-death-via-lfa-1-icam-1-interaction-in-a-mouse-model-of-parkinson-s-disease
#17
Zhan Liu, Yan Huang, Bei-Bei Cao, Yi-Hua Qiu, Yu-Ping Peng
T helper (Th)17 cells, a subset of CD4(+) T lymphocytes, have strong pro-inflammatory property and appear to be essential in the pathogenesis of many inflammatory diseases. However, the involvement of Th17 cells in Parkinson's disease (PD) that is characterized by a progressive degeneration of dopaminergic (DAergic) neurons in the nigrostriatal system is unclear. Here, we aimed to demonstrate that Th17 cells infiltrate into the brain parenchyma and induce neuroinflammation and DAergic neuronal death in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)- or 1-methyl-4-phenylpyridinium (MPP(+))-induced PD models...
November 14, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27844281/novel-neuroprotective-effects-of-melanin-concentrating-hormone-in-parkinson-s-disease
#18
Ji-Yeun Park, Seung-Nam Kim, Junsang Yoo, Jaehwan Jang, Ahreum Lee, Ju-Young Oh, Hongwon Kim, Seung Tack Oh, Seong-Uk Park, Jongpil Kim, Hi-Joon Park, Songhee Jeon
Acupuncture has shown the therapeutic effect on various neurodegenerative disorders including Parkinson's disease (PD). While investigating the neuroprotective mechanism of acupuncture, we firstly found the novel function of melanin-concentrating hormone (MCH) as a potent neuroprotective candidate. Here, we explored whether hypothalamic MCH mediates the neuroprotective action of acupuncture. In addition, we aimed at evaluating the neuroprotective effects of MCH and elucidating underlying mechanism in vitro and in vivo PD models...
November 14, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27836641/2-3-cyclic-nucleotide-3-phosphodiesterase-as-a-messenger-of-protection-of-the-mitochondrial-function-during-melatonin-treatment-in-aging
#19
Yulia Baburina, Irina Odinokova, Tamara Azarashvili, Vladimir Akatov, John J Lemasters, Olga Krestinina
The process of aging is considered to be tightly related to mitochondrial dysfunction. One of the causes of aging is an increased sensitivity to the induction of mitochondrial permeability transition pore (mPTP) opening in the inner membrane of mitochondria. Melatonin, a natural antioxidant, is a hormone produced by the pineal gland. The role of melatonin whose level decreases with aging is well understood. In the present study, we demonstrated that long-term treatment of aged rats with melatonin improved the functional state of mitochondria; thus, the Ca(2+) capacity was enhanced and mitochondrial swelling was deaccelerated in mitochondria...
November 9, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27834780/cyclophilin-d-promotes-brain-mitochondrial-f1fo-atp-synthase-dysfunction-in-aging-mice
#20
Esha Gauba, Lan Guo, Heng Du
Brain aging is the known strongest risk factor for Alzheimer's disease (AD). In recent years, mitochondrial deficits have been proposed to be a common mechanism linking brain aging to AD. Therefore, to elucidate the causative mechanisms of mitochondrial dysfunction in aging brains is of paramount importance for our understanding of the pathogenesis of AD, in particular its sporadic form. Cyclophilin D (CypD) is a specific mitochondrial protein. Recent studies have shown that F1FO ATP synthase oligomycin sensitivity conferring protein (OSCP) is a binding partner of CypD...
November 5, 2016: Journal of Alzheimer's Disease: JAD
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