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Cristina Maccallini, Mauro Di Matteo, Marialucia Gallorini, Monica Montagnani, Valentina Graziani, Alessandra Ammazzalorso, Pasquale Amoia, Barbara De Filippis, Sara Di Silvestre, Marialuigia Fantacuzzi, Letizia Giampietro, Maria A Potenza, Nazzareno Re, Assunta Pandolfi, Amelia Cataldi, Rosa Amoroso
In mammalian cells, aberrant iNOS induction may have detrimental consequences, and seems to be involved in the proliferation and progression of different tumors, such as malignant gliomas. Therefore, selective inhibition of iNOS could represent a feasible therapeutic strategy to treat these conditions. In this context, we have previously disclosed new acetamidines able to inhibit iNOS with a very high selectivity profile over eNOS or nNOS. Here we report the synthesis of a new series of compounds structurally related to the leading scaffold of N-[(3-aminomethyl)benzyl] acetamidine (1400 W), together with their in vitro activity and selectivity...
April 13, 2018: European Journal of Medicinal Chemistry
Q-M Wang, X-Y Zhao, Z Wang, X-B Yang
OBJECTIVE: Amblyopia or lazy eye is a common visual problem affecting children that cannot correct with lenses. Nitric oxide synthase (NOS) is a critical enzyme that regulates the activity of nitric oxide (NO), a key signaling molecule with multiple roles in many tissues. Among its many activities, NOS has been proposed to be required for normal eye development and altered NOS expression can lead to perturbations in eye development and vision. MATERIALS AND METHODS: To examine the potential role of neuronal NOS (nNOS) in vision loss, we generated a model of monocular deprivation amblyopia in rats...
April 2018: European Review for Medical and Pharmacological Sciences
Oliver Baum, Dea Aaldijk, Anna Lena Engeli, Matthias Spree, Serge Summermatter, Christoph Handschin, Andreas Zakrzewicz
The expression of neuronal NO synthase (nNOS) alpha- and beta-isoforms in skeletal muscle is well documented but only little information is available about their regulation/functions. Using different mouse models, we now assessed whether the expression of nNOS-isoforms in muscle fibers is related to mitochondria content/activity and regulated by peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha). Catalytic histochemistry revealed highest nNOS-concentrations to be present in type-2 oxidative muscle fibers...
April 17, 2018: Nitric Oxide: Biology and Chemistry
Natasha Najwa Nor Arfuzir, Renu Agarwal, Igor Iezhitsa, Puneet Agarwal, Sabrilhakim Sidek, Alexander Spasov, Alexander Ozerov, Nafeeza Mohd Ismail
PURPOSE: Retinal ganglion cell apoptosis in glaucoma is associated with elevated levels of endothelin-1 (ET1), a potent vasoconstrictor. ET1-induced retinal ischemia leads to altered expression of nitric oxide synthase (NOS) isoforms leading to increased formation of nitric oxide (NO) and retinal nitrosative stress. Since magnesium (Mg) is known to improve endothelial functions and reduce oxidative stress and taurine (TAU) possesses potent antioxidant properties, we investigated the protective effects of magnesium acetyltaurate (MgAT) against ET1-induced nitrosative stress and retinal damage in rats...
April 20, 2018: Current Eye Research
Anne D M Riquier-Brison, Arnold Sipos, Ágnes Prókai, Sarah L Vargas, Ildiko Toma, Elliott J Meer, Karie G Villanueva, Jennifer C M Chen, Georgina Gyarmati, Christopher Yih, Elaine Tang, Bahram Nadim, Sujith Pendekanti, Ingrid M Garrelds, Genevieve Nguyen, A H Jan Danser, Janos Peti-Peterdi
The prorenin receptor (PRR) was originally proposed to be a member of the renin-angiotensin system (RAS), however recent work questioned their association. The present paper describes a functional link between the PRR and RAS in the renal juxtaglomerular apparatus (JGA), a classic anatomical site of the RAS. PRR expression was found in the sensory cells of the JGA, the macula densa (MD), and immunohistochemistry localized PRR to the MD basolateral cell membrane in mouse, rat, and human kidneys. MD cell PRR activation led to MAP kinase ERK1/2 signaling and stimulation of PGE2 release, the classic pathway of MD-mediated renin release...
April 18, 2018: American Journal of Physiology. Renal Physiology
Mohamed Abdellah Ibrahim, Ayman Geddawy, Soha Abdel-Wahab
Ischemic heart disease is a common cause of mortality worldwide. Sitagliptin is a new anti-diabetic drug acting as dipeptidyl peptidase-4 (DPP-4) inhibitor. The study investigated the ability of sitagliptin to prevent pathological changes of isoproterenol- (ISO-) induced myocardial injury in rats. The role of nitric oxide (NO) was also reported. Rats were assorted into six groups (n = 7) and treated for 12 days. Group 1: normal control, received normal saline. Group 2, sitagliptin control, received sitagliptin (10mg/kg, orally)...
April 12, 2018: European Journal of Pharmacology
Giulia Costa, Micaela Morelli, Nicola Simola
Previous studies have consistently demonstrated that the amphetamine-related drug 3,4-methylenedioxymethamphetamine (MDMA) induces dopaminergic damage in the mouse brain, and that this effect is most marked in the nigrostriatal system. Moreover, it has been suggested that the overproduction of nitric oxide (NO) may participate in the dopaminergic damage induced by MDMA. To further elucidate this issue, we evaluated the levels of the enzyme nitric oxide synthase (nNOS), which catalyzes the production of NO, in mice treated with regimens of MDMA that induce progressive and persistent neurotoxicity in the dopaminergic nigrostriatal system...
April 9, 2018: Neurotoxicity Research
Minmin Tian, Fangfang Liu, Han Liu, Qiong Zhang, Lei Li, Xiangbo Hou, Jianxin Zhao, Sheng Li, Xuhong Chang, Yingbiao Sun
Cisplatin (CIS) is widely applied for its antihematological malignancies properties and as antisolid tumors drugs. However, it could cause testicular damage related with oxidative stress and testosterone synthesis disorder. Studies reported that grape seed procyanidins extract (GSPE) could improve CIS induced-testes lesion via scavenging free radicals in animals, although its mechanisms were unclear. Therefore, the purpose of the present study was to explore the antagonistic mechanisms of GSPE on CIS-induced testes lesion...
April 3, 2018: Systems Biology in Reproductive Medicine
Hong-Liang He, Lin-Li Pan, Xiao-Li Gu, Jiao-Jiao Huang, Cheng-Hong Sun, Yu-Lin Tang, Li-Na Chen
Magnetic molecularly imprinted polymers(MMIPs) were prepared with ZL006 as template, acrylamide(AA) as the functional monomer, and acetonitrile as pore-forming agent; then Fourier transform infrared spectroscopy(FT-IR) and scanning electron microscopy(SEM) were used to characterize their forms and structures. Simultaneously, the MMIPs prepared previously were used as sorbents for dispersive magnetic solid phase extraction(DSPE) to capture and identify potential nNOS-PSD-95 uncouplers from extracts of Trifolium pratense and the the activities of the screened compounds were evaluated by the neuroprotective effect and co-immunoprecipitation test...
February 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Mi Jung Kim, Hye Jin Yang, Younghoon Kim, Insug Kang, Sung Soo Kim, Young-Wuk Cho
Serotonergic neurons in the dorsal raphe nucleus (DRN) act as wake-inducing neurons in the sleep-wake cycle and are controlled by gamma-aminobutyric acid (GABA) synaptic inputs. We investigated daily changes in GABAergic inhibition of the rat DRN neurons and the role of nitric oxide (NO) and cation-chloride co-transporters in the GABAergic action. Neuronal NO synthase (nNOS) was co-expressed in 74% of serotonergic DRN neurons and nNOS expression was higher during daytime (the sleep cycle) than that during nighttime (the wake cycle)...
March 27, 2018: Neuropharmacology
Chunxue Zhou, Suraj B Teegala, Bilal A Khan, Christina Gonzalez, Vanessa H Routh
Hypoglycemia is a profound threat to the brain since glucose is its primary fuel. As a result, glucose sensors are widely located in the central nervous system and periphery. In this perspective we will focus on the role of hypothalamic glucose-inhibited (GI) neurons in sensing and correcting hypoglycemia. In particular, we will discuss GI neurons in the ventromedial hypothalamus (VMH) which express neuronal nitric oxide synthase (nNOS) and in the perifornical hypothalamus (PFH) which express orexin. The ability of VMH nNOS-GI neurons to depolarize in low glucose closely parallels the hormonal response to hypoglycemia which stimulates gluconeogenesis...
2018: Frontiers in Physiology
Yuanyuan Ding, Peng Yao, Tao Hong, Hongxi Li, Yongqiang Zhu, Zhenkai Han, Guangyu Zhou
Objective To observe the analgesic effect of early hyperbaric oxygen (HBO) treatment in chronic constriction injury (CCI) rats, and to analyze the influence of HBO on the expression of neuronal nitric oxide synthase and inducible nitric oxide synthase and on the levels of inflammatory factors. Methods Rats were assigned into three groups randomly: sham, CCI, and HBO groups. The CCI rat model was established, and HBO treatment at 2.5 ATA (60 min) was given one day after surgery, lasting for five consecutive days...
January 2018: Molecular Pain
Jing Zhou, Gang Cheng, Hua Pang, Qian Liu, Ying Liu
Accumulating evidence has shown that hypothyroidism affects the cardiovascular system, significantly increasing the incidence of cardiovascular diseases. In the present study we investigated the effect of radioactive iodine (I-131)-induced hypothyroidism on several parameters of vascular function, such as nitric oxide (NO), total nitric oxide synthase (NOS) activity and expression of NOS isoforms, as well as on interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) as indicators of inflammation, in rats...
March 10, 2018: Bosnian Journal of Basic Medical Sciences
Yu Zhang, Zhu Zhu, Hai-Ying Liang, Lei Zhang, Qi-Gang Zhou, Huan-Yu Ni, Chun-Xia Luo, Dong-Ya Zhu
In neurons, increased protein-protein interactions between neuronal nitric oxide synthase (nNOS) and its carboxy-terminal PDZ ligand (CAPON) contribute to excitotoxicity and abnormal dendritic spine development, both of which are involved in the development of Alzheimer's disease. In models of Alzheimer's disease, increased nNOS-CAPON interaction was detected after treatment with amyloid-β in vitro, and a similar change was found in the hippocampus of APP/PS1 mice (a transgenic mouse model of Alzheimer's disease), compared with age-matched background mice in vivo...
March 25, 2018: Aging Cell
Xiaowen Cheng, Martina Svensson, Yiyi Yang, Tomas Deierborg, Eva Ekblad, Ulrikke Voss
Reduced blood flow to the brain induces cerebral ischaemia, potentially causing central injury and peripheral complications including gastrointestinal (GI) dysfunction. The pathophysiology behind GI symptoms is suspected to be neuropathy in the enteric nervous system (ENS), which is essential in regulating GI function. This study investigates if enteric neuropathy occurs after cerebral ischaemia, by analysing neuronal survival and relative numbers of vasoactive intestinal peptide (VIP) and neuronal nitric oxide synthase (nNOS) expressing neurons in mouse ileum after three types of cerebral ischaemia...
March 25, 2018: International Journal of Experimental Pathology
Hande Parlak, Ayse Ozkan, Sayra Dilmac, Gamze Tanriover, Ozlem Ozsoy, Aysel Agar
INTRODUCTION: Docosahexaenoic acid (DHA) has been shown to have beneficial effects on Parkinson's disease (PD). The aim of this study was to investigate if the DHA acts on neurons of substantia nigra (SN) by phosphorylation of neuronal nitric oxide synthase (nNOS) in an experimental mouse model of PD. MATERIAL AND METHODS: An experimental model of PD was created by intraperitoneal injections (4 x 20 mg/kg) of the neurotoxin 1-methyl-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)...
March 26, 2018: Folia Histochemica et Cytobiologica
Ashok Iyaswamy, Ananth Kumar Kammella, Citarasu Thavasimuthu, Wankhar Wankupar, Wankhar Dapkupar, Sambantham Shanmugam, Ravindran Rajan, Sheeladevi Rathinasamy
Many controversial reports are available on the use of aspartame as it releases methanol as one of its metabolite during metabolism. The present study proposes to investigate whether long term (90 days) aspartame (40 mg/kg b.wt) administration could induce oxidative stress and alter the memory in Wistar strain male albino rats. To mimic the human methanol metabolism, methotrexate (MTX)-treated rats were included as a model to study the effects of aspartame. Wistar strain albino rats were administered with aspartame (40 mg/kg b...
April 2018: Journal of Food and Drug Analysis
Ryuta Kikuchi, Kimiharu Ambe, Hideki Kon, Satoshi Takada, Hiroki Watanabe
Localization of the nitric oxide (NO)-producing enzyme, nitric oxide synthase (NOS), and its functions are currently being investigated in several tissues and organs. It has been suggested that NO is involved in nerve cell death and the development of neurodegenerative disease. The purpose of this study was to immunohistochemically investigate expression of NOS to clarify its function in the degeneration and regeneration of transected mouse sciatic nerve. Scattered neuronal NOS (nNOS)-positive Schwann cells observed on the central side of the stump on day 1 after transection showed an increase in number on day 7...
2018: Bulletin of Tokyo Dental College
Hossein Amini-Khoei, Nastaran Kordjazy, Arya Haj-Mirzaian, Shayan Amiri, Arvin Haj-Mirzaian, Armin Shirzadian, Amin Hasanvand, Shima Balali-Dehkordi, Mahsa Hassanipoor, Ahmad Reza Dehpour
Anticonvulsant effects of minocycline have been explored recently. This study was designed to examine the anticonvulsant effect of acute administration of minocycline on pentylenetetrazole (PTZ)-induced seizures in mouse considering the possible role of nitric oxide (NO)/NMDA pathway. We induced seizure using intravenous administration of PTZ. Our results showed that acute administration of minocycline increased the seizure threshold. Furthermore, co-administration of sub-effective doses of the non-selective nitric oxide synthase (NOS) inhibitor, L-NAME (10 mg/kg) and the neuronal NOS inhibitor, 7-nitroindazole (40 mg/kg) enhanced the anticonvulsant effect of sub-effective dose of minocycline (40 mg/kg)...
March 20, 2018: Canadian Journal of Physiology and Pharmacology
Fernando Francisco Borges Resende, Simoneide Souza Titze-de-Almeida, Ricardo Titze-de-Almeida
Astrocytic tumors, including astrocytomas and glioblastomas, are the most common type of primary brain tumors. Treatment for glioblastomas includes radiotherapy, chemotherapy with temozolomide (TMZ) and surgical ablation. Despite certain therapeutic advances, the survival time of patients is no longer than 12-14 months. Cancer cells overexpress the neuronal isoform of nitric oxide synthase (nNOS). In the present study, it was examined whether the nNOS enzyme serves a role in the damage of astrocytoma (U251MG and U138MG) and glioblastoma (U87MG) cells caused by TMZ...
April 2018: Oncology Letters
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