Nitric oxide synthase expression and enzymatic activity in multiple sclerosis

Broholm, Helle; Andersen, B.; Wanscher, Benedikte; Frederiksen, Jette Lautrup; Rubin, Inger; Pakkenberg, Bente; Larsson, H. B. W.; Lauritzen, Martin

doi:10.1111/j.1600-0404.2004.00207.x

Cited by 86 publications

(70 citation statements)

References 36 publications

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“…There is some evidence for increase in M1 macrophage populations in MS (8,12,13) but M1/M2 macrophage profile during disease genesis in MS and EAE has been poorly studied. It is unclear how this differentiation occurs, what factors influenced this process during disease and whether artificially manipulating the balance from one subset to the other affect outcome of acute neuroinflammation.…”

mentioning

confidence: 99%

Activation of Invariant NKT Cells in Early Phase of Experimental Autoimmune Encephalomyelitis Results in Differentiation of Ly6Chi Inflammatory Monocyte to M2 Macrophages and Improved Outcome

Denney

Kok

Cole

et al. 2012

The Journal of Immunology

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Neuropathology in multiple sclerosis is closely linked to presence of macrophages in the CNS. Both M1 (inflammatory) and M2 (alternatively activated, noninflammatory) macrophages are found in the inflamed CNS and thought to differentiate from infiltrating monocytes. It is unclear whether the balance of M1 and M2 macrophages can be altered and whether this affects disease outcome. We show in this article that Ly6Chi inflammatory monocytes are the early and dominant infiltrating cells in the CNS during experimental autoimmune encephalomyelitis, a model for the acute phase of multiple sclerosis. Activation of invariant NKT (iNKT) cells reduced the frequency of Ly6Chi monocytes and increased the proportion of M2 macrophages in the CNS with associated improvement in neurologic impairment. In contrast, iNKT-deficient mice showed higher numbers of Ly6Chi monocytes, reduced M2, and much more severe disease. Adoptive transfer of M2-enriched cells to iNKT-deficient mice markedly improved neurologic impairment. In vitro and in vivo experiments showed that iNKT cells promote differentiation of monocytes to M2 macrophages in an IL-4 and CD1d-dependent process. These findings indicate that infiltrating Ly6Chi inflammatory monocytes are early players in acute neuroinflammation and that their frequency and differentiation can be influenced by activation of iNKT cells with resultant improvement in disease outcome.

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mentioning

confidence: 99%

Activation of Invariant NKT Cells in Early Phase of Experimental Autoimmune Encephalomyelitis Results in Differentiation of Ly6Chi Inflammatory Monocyte to M2 Macrophages and Improved Outcome

Denney

Kok

Cole

et al. 2012

The Journal of Immunology

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“…In addition, NOS enzymatic activity has been shown to be regulated by multiple factors (Alderton et al 2001). As a consequence, the expression and activity of the enzyme might not always be correlated (Broholm et al 2003). Our kinetic studies show that a fully active NOS is present in the CNS of T. infestans, and that this enzyme shares similar cofactor requirements with other insect NOS (Ribeiro and Nussenzveig 1993;Müller 1994).…”

Section: Molecular and Biochemical Properties Of Nos In T Infestansmentioning

confidence: 86%

Distribution and characterization of nitric oxide synthase in the nervous system of Triatoma infestans (Insecta: Heteroptera)

Settembrini

Coronel

Nowicki³

et al. 2007

Cell Tissue Res

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The biochemical characterization of nitric oxide synthase (NOS) and its distribution in the central nervous system (CNS) were studied in the heteropteran bug Triatoma infestans. NOS-like immunoreactivity was found in the brain, subesophageal ganglion, and thoracic ganglia by using immunocytochemistry. In the protocerebrum, NOS-immunoreactive (IR) somata were detected in the anterior, lateral, and posterior soma rinds. In the optic lobe, numerous immunostained somata were observed at the level of the first optic chiasma, around the lobula, and in the proximal optic lobe. In the deutocerebrum, NOS-IR perikarya were mainly observed in the lateral soma rind, surrounding the sensory glomeruli, and a few cell bodies were seen in association with the antennal mechanosensory and motor neuropil. No immunostaining could be detected in the antennal nerve. The subesophageal and prothoracic ganglia contained scattered immunostained cell bodies. NOS-IR somata were present in all the neuromeres of the posterior ganglion. Western blotting showed that a universal NOS antiserum recognized a band at 134 kDa, in agreement with the expected molecular weight of the protein. Analysis of the kinetics of nitric oxide production revealed a fully active enzyme in tissue samples of the CNS of T. infestans.

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“…NO activity has been extensively studied in tumor biology (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28). It appears to be involved in all phases of carcinogenesis (12).…”

Section: Effects Of Nitric Oxide Synthase Deficiency On a Disintegrinmentioning

confidence: 99%

“…Furthermore, increased nNOS expression has been observed in glial neoplasms. The highest nNOS values were observed in world health organization (WHO) grade III and IV tumors, and in carcinoma and melanoma metastasic tissues, whereas no or low nNOS expression was observed in WHO grade I or II tumors, and in meningiomas (20,21). iNOS expression is induced in different types of human brain tumors, including gliomas (22), where it is known to promote glioma stem cell proliferation and tumor growth (23).…”

Section: Effects Of Nitric Oxide Synthase Deficiency On a Disintegrinmentioning

confidence: 99%

Effects of nitric oxide synthase deficiency on a disintegrin and metalloproteinase domain-containing protein 12 expression in mouse brain samples

Lendeckel¹,

Wolke²,

Bernstein

et al. 2015

Molecular Medicine Reports

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Abstract.A d isi nt eg r i n a nd met a l loprot ei nase domain-containing protein 12 (ADAM12) belongs to the ADAM family of transmembrane proteins. Via proteolysis, cell adhesion, cell-cell fusion, cell-matrix interaction and membrane protein shedding, ADAM proteins are involved in normal brain development, and also in cancer genesis and progression, and in inflammation. Therefore, neurobiological research focusing on this protein is increasing. Nitric oxide (NO), which is endogenously produced by NO synthases (NOS), is associated with glial tumors. However, knock-out of NOS produces only limited antitumor effects. The present study analyzed the expression of ADAM12 in the cortex and hippocampus of C57/BL6 wild-type mice, and endothelial NOS-, neuronal NOS-(nNOS) or inducible NOS (iNOS)-deficient ( -/-) mice, at different stages of development. Expression of ADAM12 was quantified using immunoblot analysis of cortical and hippocampal tissue samples from fetal, neonatal (5 days postnatal), adult (12 weeks old) or >1 year old mice. Using reverse transcription-quantitative polymerase chain reaction, ADAM12 expression was analyzed in cultured N9, OLN93, C6 and PC12 cells, representing the four main cell types in the brain, following NOS inhibition. ADAM12 expression was low in all mouse genotypes and regions of the brain, and in fetal and neonatal mice, an increase in expression was observed with increasing age. The highest levels of expression were observed in the cortex of adult mice, iNOS -/-mice of >1 year and wild-type mice, and in the hippocampus of adult and iNOS -/-mice of >1 year. By contrast, ADAM12 expression was lowest in adult nNOS -/-mice. Inhibition of NOS using N ω -Nitro-L-arginine methyl ester hydrochloride, induced ADAM12 mRNA expression in N9 and PC12 cell lines. Inhibition of NOS using L-N 6 -(1-Iminoethyl)lysine dihydrochloride, induced ADAM12 mRNA expression in N9 and C6 cell lines. No change in ADAM12 expression was observed in OLN93 cells following NOS inhibition. ADAM12 expression in mouse hippocampus and cortex samples demonstrated considerable variation during development, with a marked increase observed in adult and >1 year old mice, compared with that in fetal and neonatal mice. IntroductionNitric oxide (NO) is an important signaling molecule found in animals, including humans. Reduced NO production is associated with important cardiovascular risk factors, such as hyperlipidemia (1,2), diabetes, hypertension, smoking, atherosclerosis and aging (3). The bioavailability of NO in cells and tissues decreases with age. This may be a result of a decrease in the expression of the constitutive isoforms [endothelial nitric oxide synthase (eNOS) and neuronal NOS (nNOS)], with age (4). Inducible NOS (iNOS)-mediated NO formation has been shown to affect longevity. In mice, iNOS overexpression may lead to increased mortality, which is associated with cardiac hypertrophy and sudden cardiac death as a result of bradyarrhythmias (5). iNOS expression is typically not observed in the brains of young (1-3...

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Nitric oxide synthase expression and enzymatic activity in multiple sclerosis

Cited by 86 publications

References 36 publications

Activation of Invariant NKT Cells in Early Phase of Experimental Autoimmune Encephalomyelitis Results in Differentiation of Ly6Chi Inflammatory Monocyte to M2 Macrophages and Improved Outcome

Activation of Invariant NKT Cells in Early Phase of Experimental Autoimmune Encephalomyelitis Results in Differentiation of Ly6Chi Inflammatory Monocyte to M2 Macrophages and Improved Outcome

Distribution and characterization of nitric oxide synthase in the nervous system of Triatoma infestans (Insecta: Heteroptera)

Effects of nitric oxide synthase deficiency on a disintegrin and metalloproteinase domain-containing protein 12 expression in mouse brain samples

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