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https://www.readbyqxmd.com/read/29458127/calmodulin-induced-conformational-control-and-allostery-underlying-neuronal-nitric-oxide-synthase-activation
#1
Quinlin M Hanson, Jeffrey R Carley, Tyler J Gilbreath, Brian C Smith, Eric S Underbakke
Nitric oxide synthase (NOS) is the primary generator of nitric oxide signals controlling diverse physiological processes such as neurotransmission and vasodilation. NOS activation is contingent on Ca2+ /calmodulin binding at a linker between its oxygenase and reductase domains to induce large conformational changes that orchestrate inter-domain electron transfer. However, the structural dynamics underlying activation of full-length NOS remain ambiguous. Employing hydrogen-deuterium exchange mass spectrometry, we reveal mechanisms underlying neuronal NOS (nNOS) activation by calmodulin and regulation by phosphorylation...
February 16, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29453425/chronic-treatment-with-fluoride-affects-the-jejunum-insights-from-proteomics-and-enteric-innervation-analysis
#2
Aline Salgado Dionizio, Carina Guimarães Souza Melo, Isabela Tomazini Sabino-Arias, Talita Mendes Silva Ventura, Aline Lima Leite, Sara Raquel Garcia Souza, Erika Xavier Santos, Alessandro Domingues Heubel, Juliana Gadelha Souza, Juliana Vanessa Colombo Martins Perles, Jacqueline Nelisis Zanoni, Marília Afonso Rabelo Buzalaf
Gastrointestinal symptoms are the first signs of fluoride (F) toxicity. In the present study, the jejunum of rats chronically exposed to F was evaluated by proteomics, as well as by morphological analysis. Wistar rats received water containing 0, 10 or 50 mgF/L during 30 days. HuC/D, neuronal Nitric Oxide (nNOS), Vasoactive Intestinal Peptide (VIP), Calcitonin Gene Related Peptide (CGRP), and Substance P (SP) were detected in the myenteric plexus of the jejunum by immunofluorescence. The density of nNOS-IR neurons was significantly decreased (compared to both control and 10 mgF/L groups), while the VIP-IR varicosities were significantly increased (compared to control) in the group treated with the highest F concentration...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29447430/aucubin-protects-against-pressure-overload-induced-cardiac-remodelling-via-%C3%AE-3-ar-nnos-cascades
#3
Qing-Qing Wu, Yang- Xiao, Ming-Xia Duan, Yuan Yuan, Xiao-Han Jiang, Zheng Yang, Hai-Han Liao, Wei Deng, Qi-Zhu Tang
BACKGROUND AND PURPOSE: Aucubin, the predominant component of Eucommia ulmoides Oliv., plays an indispensable role in regulating oxidative stress. Considering that oxidative stress has previously been demonstrated to contribute to acute and chronic myocardial injury, we tested the effects of aucubin on cardiac remodelling and heart failure. EXPERIMENTAL APPROACH: In the first set of experiments, H9c2 cardiomyocytes and neonatal rat cardiomyocytes pre-treated with aucubin (1, 3 10, 25, 50 μM) were challenged with phenylephrine...
February 15, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29447059/therapeutic-potential-of-mucuna-pruriens-linn-on-ageing-induced-damage-in-dorsal-nerve-of-the-penis-and-its-implication-on-erectile-function-an-experimental-study-using-albino-rats
#4
Prakash Seppan, Ibrahim Muhammed, Karthik Ganesh Mohanraj, Ganesh Lakshmanan, Dinesh Premavathy, Sakthi Jothi Muthu, Khayinmi Wungmarong Shimray, Sathya Bharathy Sathyanathan
OBJECTIVE: To study the effect of ethanolic seed extract of Mucuna pruriens on damaged dorsal nerve of the penis (DNP) in aged rat in relation to penile erection. METHODS: The rats were divided into four groups Young (3 months), Aged (24 - 28 months), Aged + M. pruriens, and Young + M. pruriens (200 mg/kg b.w/60 days) and were subjected to the hypophysial - gonadal axis, nerve conduction velocity (NCV), and penile reflex. DNP sections were stained with nitric oxide synthase (nNOS), nicotinamide adenine dinucleotide phosphate (NaDPH) diaphorase, androgen receptor (AR), and osmium tetroxide...
February 15, 2018: Aging Male: the Official Journal of the International Society for the Study of the Aging Male
https://www.readbyqxmd.com/read/29439324/altered-expression-of-urea-cycle-enzymes-in-amyloid-%C3%AE-protein-precursor-overexpressing-pc12-cells-and-in-sporadic-alzheimer-s-disease-brain
#5
Henryk Jęśko, Walter J Lukiw, Anna Wilkaniec, Magdalena Cieślik, Magdalena Gąssowska-Dobrowolska, Emilia Murawska, Wojciech Hilgier, Agata Adamczyk
Urea cycle enzymes may play important yet poorly characterized roles in Alzheimer's disease (AD). Our previous results showed that amyloid-β (Aβ) affects urea cycle enzymes in rat pheochromocytoma (PC12) cells. The aim of the present study was to investigate the changes in arginases, other urea cycle enzymes, and nitric oxide synthases (NOSs) in PC12 cells transfected with AβPP bearing the double 'Swedish' mutation (APPsw, K670M/N671L) and in postmortem sporadic AD brain hippocampus; the mutation intensifies Aβ production and strongly associates with AD neuropathology...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29438803/sleep-state-dependence-of-optogenetically-evoked-responses-in-neuronal-nitric-oxide-synthase-positive-cells-of-the-cerebral-cortex
#6
Dmitry Gerashchenko, Michelle A Schmidt, Mark R Zielinski, Michele E Moore, Jonathan P Wisor
Slow-wave activity (SWA) in the electroencephalogram during slow-wave sleep (SWS) varies as a function of sleep-wake history. A putative sleep-active population of neuronal nitric oxide synthase (nNOS)-containing interneurons in the cerebral cortex, defined as such by the expression of Fos in animals euthanized after protracted deep sleep, may be a local regulator of SWA. We investigated whether electrophysiological responses to activation of these cells are consistent with their role of a local regulator of SWA...
February 10, 2018: Neuroscience
https://www.readbyqxmd.com/read/29421244/involvement-of-no-nmda-r-pathway-in-the-behavioral-despair-induced-by-amphetamine-withdrawal
#7
Arvin Haj-Mirzaian, Shayan Amiri, Hossein Amini-Khoei, Arya Haj-Mirzaian, Arsalan Hashemiaghdam, Kiana Ramezanzadeh, Maria Ghesmati, Khashayar Afshari, Ahmad Reza Dehpour
Abrupt discontinuation of chronic amphetamine consumption leads to withdrawal symptoms including depression, anhedonia, dysphoria, fatigue, and anxiety. These irritating symptoms may result in continuing to take the drug or can lead to suicidal behavior. Past studies have shown the involvement of various biologic systems in depression induced following amphetamine withdrawal (AW). However, there is no evidence about the relation between nitric oxide (NO) with NMDA receptors on depression following AW. In this study, we examined the involvement of the NO/NMDA pathways on depressive-like behaviors after 24 h withdrawal following 5 continuous days of amphetamine administration in male NMRI mice...
February 5, 2018: Brain Research Bulletin
https://www.readbyqxmd.com/read/29414777/a-cross-domain-charge-interaction-governs-the-activity-of-no-synthase
#8
Mohammad Mahfuzul Haque, Jesus Tejero, Mekki Bayachou, Claire T Kenney, Dennis J Stuehr
NO synthase (NOS) enzymes perform inter-domain electron transfer reactions during catalysis that may rely on complementary charge interactions at domain-domain interfaces. Guided by our previous results and a computer-generated domain docking model, we assessed the importance of cross-domain charge interactions in the FMN to heme electron transfer in neuronal NOS (nNOS). We reversed the charge of three residues (Glu-762, Glu-816, Glu-819) that form an electronegative triad on the FMN domain, and then individually reversed the charges of three electropositive residues (Lys-423, Lys-620, Lys-660) on the oxygenase domain (NOSoxy), to potentially restore a cross-domain charge interaction with the triad, but in reversed polarity...
February 2, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29414029/control-of-cardiovascular-responses-to-stress-by-crf-in-the-bed-nucleus-of-stria-terminalis-is-mediated-by-local-nmda-nnos-sgc-pkg-signaling
#9
Leandro A Oliveira, Lucas Gomes-de-Souza, Ricardo Benini, Carlos C Crestani
The aims of the present study were to assess an interaction of corticotropin-releasing factor (CRF) neurotransmission within the bed nucleus of the stria terminalis (BNST) with local nitrergic signaling, as well as to investigate an involvement of activation of local NMDA glutamate receptor and nitric oxide (NO) signaling in control of cardiovascular responses to acute restraint stress by BNST CRF neurotransmission in rats. We observed that CRF microinjection into the BNST increased local NO release during restraint stress...
January 12, 2018: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/29413901/mir-137-3p-rescue-motoneuron-death-by-targeting-calpain-2
#10
Ying Tang, Rao Fu, Ze-Min Ling, Lin-Lin Liu, Guang-Yin Yu, Wen Li, Xin-Yu Fang, Zhe Zhu, Wu-Tian Wu, Li-Hua Zhou
Brachial plexus root avulsion (BPRA) is a type of injury that leads to motor function loss as a result of motoneurons (MNs) degeneration. Here we identified that the reduced expression of rat miR-137-3p in the ventral horn of spinal cord was associated with MNs death. However, the pathophysiological role of miR-137-3p in root avulsion remains poorly understood. We demonstrated that the calcium-activated neutral protease-2 (calpain-2) was a direct target gene of miR-137-3p with miR-137-3p binding to the 3'-untranslated region of calpain-2...
January 26, 2018: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/29413528/nitric-oxide-signaling-in-neurodegeneration-and-cell-death
#11
Ted M Dawson, Valina L Dawson
In this tribute to Solomon H. Snyder (Sol) we discuss the mechanisms by which nitric oxide (NO) kills neurons. We provide a historical perspective regarding the discovery that glutamate excitotoxicity is mediated by NO. It also contains a discussion of the discovery that neuronal nitric oxide synthase (nNOS) catalytic activity accounts for NADPH diaphorase activity and its localization in the central nervous system. NADPH diaphorase/nNOS neurons are unique in that they are resistant to toxic effects of excess glutamate and that they are resistant to neurodegeneration in a variety of neurodegenerative diseases...
2018: Advances in Pharmacology
https://www.readbyqxmd.com/read/29410249/biphasic-effect-of-sumatriptan-on-ptz-induced-seizures-in-mice-modulation-by-5-ht1b-d-receptors-and-nos-no-pathway
#12
Maziar Gooshe, Keyvan Ghasemi, Mohammad Mojtaba Rohani, Abbas Tafakhori, Shayan Amiri, Vajiheh Aghamollaii, Mona Ahmadi, Ahmad Reza Dehpour
Sumatriptan has been among the top choices in the management of migraine headaches. The association between migraine and epilepsy highlights the possible effect of sumatriptan on seizures. In this regard, we investigated sumatriptan effects on PTZ-induced seizures thresholds and delineated the modulatory role of 5-HT1B/D receptors and NOS/NO pathway. Our data revealed the anti-convulsant effects of lower doses of sumatriptan, and pro-convulsant effects of higher doses of sumatriptan. GR 127935, a selective 5-HT1B/D antagonist, could abolish the sumatriptan anti-convulsant effects, but it was ineffective against the sumatriptan pro-convulsant effects...
February 2, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29403553/grape-seed-proanthocyanidin-extract-alleviates-urethral-dysfunction-in-diabetic-rats-through-modulating-the-no-cgmp-pathway
#13
Bing Zhang, Zhaocun Zhang, Hong Ji, Hui Shi, Shouzhen Chen, Dongliang Yan, Xuewen Jiang, Benkang Shi
Oxidative stress is closely associated with the onset of diabetes mellitus (DM). Diabetic urethropathy is one of the most common complications of DM, but few studies have been conducted to investigate the role of oxidative stress in diabetic urethropathy. Grape seed proanthocyanidin extract (GSPE) has been previously reported to reduce oxidative injury. The present study aimed to investigate the role of oxidative stress and the protective effects of GSPE on urethral dysfunction using a streptozotocin-induced DM rat model...
January 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29382335/role-of-neuronal-nitric-oxide-synthase-nnos-at-medulla-in-tachycardia-induced-by-repeated-administration-of-ethanol-in-conscious-rats
#14
Jiro Hasegawa Situmorang, Hsun-Hsun Lin, Hsuan Lo, Chih-Chia Lai
BACKGROUND: Intake of ethanol (alcohol) has been shown to influence cardiovascular function; the underlying brain mechanism remains unclear. Noting that nitric oxide (NO) system in the CNS is involved in the regulation of cardiovascular function, the present study examined the role of NO in medulla in ethanol-induced cardiovascular changes. METHODS: Ethanol was administered by oral gavage at dose of 3.2 g/kg once every day for 8 consecutive days. Changes in blood pressure (BP) and heart rate (HR) in response to ethanol were measured by radiotelemetry method in freely moving female Sprague-Dawley rats...
January 31, 2018: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29372479/neuronal-nitric-oxide-synthase-is-a-novel-biomarker-for-the-interstitial-cells-of-cajal-in-stress-induced-diarrhea-dominant-irritable-bowel-syndrome
#15
Da Eun Jang, Ji Hyun Bae, Yoo Jin Chang, Yoon Hoo Lee, Ki Taek Nam, Il Yong Kim, Je Kyung Seong, Yong Chan Lee, Su Cheong Yeom
BACKGROUND: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder involving changes in normal bowel movements. The pathophysiology of IBS is not clearly understood owing to the lack of identifiable pathological abnormalities and reliable biomarkers. AIM: The aim of this study was to discover the novel and reliable biomarker for IBS. METHOD: In this study, neonatal maternal separation (NMS) stress model was used for the IBS mouse model...
January 25, 2018: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29365344/dystrophinopathy-muscle-biopsies-in-the-genetic-testing-era-one-center-s-data
#16
Courtney R Carlson, Steven A Moore, Katherine D Mathews
INTRODUCTION: Comprehensive genetic testing for dystrophinopathy can detect ∼95% of pathogenic variants in DMD and is often the preferred diagnostic approach. METHODS: We reviewed pathology reports for muscle biopsies evaluated at the University of Iowa with a pathological diagnosis of dystrophinopathy based on dystrophic histopathology and abnormal immunofluorescence staining: reduced to absent dystrophin, expression of utrophin, and loss of nNOS. RESULTS: The percentage of muscle biopsies with dystrophinopathy has been stable since 1997...
January 24, 2018: Muscle & Nerve
https://www.readbyqxmd.com/read/29361881/dimethyl-fumarate-attenuates-neuroinflammation-and-neurobehavioral-deficits-induced-by-experimental-traumatic-brain-injury
#17
Giovanna Casili, Michela Campolo, Irene Paterniti, Marika Lanza, Alessia Filippone, Salvatore Cuzzocrea, Emanuela Esposito
TBI is a serious neuropathology that causes secondary injury mechanisms, including dynamic interplay between ischemic, inflammatory and cytotoxic processes. Fumaric acid esters (FAEs) showed beneficial effects in preclinical models of neuroinflammation and toxic oxidative stress, so the aim of the present work was to evaluate the potential beneficial effects of dimethyl fumarate (DMF), the most pharmacologically effective molecules among the FAEs, in a mouse model of TBI induced by controlled cortical impact (CCI)...
January 23, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29351230/comparison-of-antioxidative-effects-of-insect-tea-and-its-raw-tea-kuding-tea-polyphenols-in-kunming-mice
#18
Xin Zhao, Jia-Le Song, Ruokun Yi, Guijie Li, Peng Sun, Kun-Young Park, Huayi Suo
Kudingcha is a traditional Chinese tea, and insect tea is a special drink produced by the metabolism of insect larvae using the raw Kuding tea. Insect tea polyphenols (ITP) and its raw tea (Kuding tea) polyphenols (KTP) are high-purity polyphenols extracted by centrifuge precipitation. The present study was designed to compare the antioxidative effects of insect tea polyphenols (ITP) and its raw tea (Kuding tea) polyphenols (KTP) on d-galactose-induced oxidation in Kunming (KM) mice. KM mice were treated with ITP (200 mg/kg) and KTP (200 mg/kg) by gavage, and vitamin C (VC, 200 mg/kg) was also used as a positive control by gavage...
January 19, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29343793/nnos-positive-minor-branches-of-the-dorsal-penile-nerves-is-associated-with-erectile-function-in-the-bilateral-cavernous-injury-model-of-rats
#19
Yen-Lin Chen, Ting-Ting Chao, Yi-No Wu, Meng-Chuan Chen, Ying-Hung Lin, Chun-Hou Liao, Chien-Chih Wu, Kuo-Chiang Chen, Shang-Shing P Chou, Han-Sun Chiang
The changes in neuronal nitric oxide synthases (nNOS) in the dorsal penile nerves (DPNs) are consistent with cavernous nerve (CN) injury in rat models. However, the anatomical relationship and morphological changes between the minor branches of the DPNs and the CNs after injury have never been clearly explored. There were forty 12 week old male Sprague-Dawley rats receiving bilateral cavernous nerve injury (BCNI). Erectile function of intracavernous pressure and mean arterial pressure were measured. The histology and ultrastructure with H&E stain, Masson's trichrome stain and immunohistochemical stains were applied on the examination of CNs and DPNs...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29319606/disruption-of-nnos-nos1ap-protein-protein-interactions-suppresses-neuropathic-pain-in-mice
#20
Wan-Hung Lee, Li-Li Li, Aarti Chawla, Andy Hudmon, Yvonne Y Lai, Michael J Courtney, Andrea G Hohmann
Elevated N-methyl-D-aspartate receptor (NMDAR) activity is linked to central sensitization and chronic pain. However, NMDAR antagonists display limited therapeutic potential due to their adverse side effects. Novel approaches targeting the NR2B-PSD95-nNOS complex to disrupt signaling pathways downstream of NMDARs show efficacy in preclinical pain models. Here, we evaluated the involvement of interactions between neuronal nitric oxide synthase (nNOS) and the nitric oxide synthase 1 adaptor protein (NOS1AP) in pronociceptive signaling and neuropathic pain...
January 9, 2018: Pain
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