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  1. Article ; Online: Significance of antibody numbering systems in the development of antibody engineering.

    Patel, Riya / Verma, Pratibha / Nagraj, Anil Kumar / Gavade, Akshata / Sharma, Om Prakash / Patil, Jaspal

    Human antibodies

    2024  Volume 31, Issue 4, Page(s) 71–80

    Abstract: Immunotherapy has become increasingly popular in recent years for treating a variety of diseases including inflammatory, neurological, oncological, and auto-immune disorders. The significant interest in antibody development is due to the high binding ... ...

    Abstract Immunotherapy has become increasingly popular in recent years for treating a variety of diseases including inflammatory, neurological, oncological, and auto-immune disorders. The significant interest in antibody development is due to the high binding affinity and specificity of an antibody against a specific antigen. Recent advances in antibody engineering have provided a different view on how to engineer antibodies in silico for therapeutic and diagnostic applications. In order to improve the clinical utility of therapeutic antibodies, it is of paramount importance to understand the various molecular properties which impact antigen targeting and its potency. In antibody engineering, antibody numbering (AbN) systems play an important role to identify the complementarity determining regions (CDRs) and the framework regions (FR). Hence, it is crucial to accurately define and understand the CDR, FR and the crucial residues of heavy and light chains that aid in the binding of the antibody to the antigenic site. Detailed understanding of amino acids positions are useful for modifying the binding affinity, specificity, physicochemical features, and half-life of an antibody. In this review, we have summarized the different antibody numbering systems that are widely used in antibody engineering and highlighted their significance. Here, we have systematically explored and mentioned the various tools and servers that harness different AbN systems.
    MeSH term(s) Humans ; Antibodies/genetics ; Antibodies/chemistry ; Complementarity Determining Regions/chemistry ; Antibody Affinity ; Binding Sites, Antibody
    Chemical Substances Antibodies ; Complementarity Determining Regions
    Language English
    Publishing date 2024-01-12
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 1383468-x
    ISSN 1875-869X ; 1093-2607
    ISSN (online) 1875-869X
    ISSN 1093-2607
    DOI 10.3233/HAB-230014
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 2936: Show issues Location:
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  2. Article ; Online: Spirulina diet to lactating mothers protects the antioxidant system and reduces inflammation in post-natal brain after systemic inflammation.

    Patil, Jaspal / Matte, Ashok / Mallard, Carina / Sandberg, Mats

    Nutritional neuroscience

    2016  Volume 21, Issue 1, Page(s) 59–69

    Abstract: Objectives: This study concerns: (1) the long-term effects of peripheral lipopolysaccharide (LPS) in neonatal rats on inflammation and antioxidant parameters in brain and (2) the effects of a Spirulina-enriched diet given to lactating mothers on ... ...

    Abstract Objectives: This study concerns: (1) the long-term effects of peripheral lipopolysaccharide (LPS) in neonatal rats on inflammation and antioxidant parameters in brain and (2) the effects of a Spirulina-enriched diet given to lactating mothers on protective and inflammatory parameters in brains of suckling pups subjected to peripheral inflammation.
    Methods: Five-day old rat pups were treated with LPS (i.p. 2 mg/kg). After 3, 7, 30, and 65 days, mRNA, miRNA, and protein levels of pro-inflammatory cytokines and the Nuclear factor E2-related factor 2 (Nrf2)-system were examined. In a sub-group, a Spirulina-enriched diet was given to the mothers 24 hours before the pups were treated with LPS, then the effects on antioxidant and inflammatory parameters were evaluated.
    Results: The main findings were: (1) interleukin 1 beta (IL-1β) was upregulated in cortex 3, 7, and 30 days after LPS treatment, (2) Nrf2 and the catalytic subunit of γ-glutamylcysteinyl ligase were decreased in cortex 7 days after LPS in parallel with increased levels of phosphorylated p38 and decreased levels of histone H3 acetylation, and (3) a Spirulina-enriched diet to lactating mothers normalized both the increased IL-1β expression and the decreased antioxidant parameters after LPS. The protective effects of Spirulina were correlated with decreased levels of phosphorylated p38 and high levels of the antioxidant miRNA-146a.
    Discussion: A Spirulina diet given to lactating mothers can protect against neuroinflammation and decreased antioxidant defence in brain of suckling pups subjected to peripheral inflammation, possibly via decreased activation of p38 and high levels of the antioxidant miRNA-146a.
    MeSH term(s) Animal Nutritional Physiological Phenomena ; Animals ; Animals, Newborn ; Antioxidants/physiology ; Brain/physiology ; Diet ; Female ; Histones/genetics ; Histones/metabolism ; Inflammation/etiology ; Inflammation/therapy ; Interleukin-1beta/genetics ; Interleukin-1beta/metabolism ; Lactation ; Lipopolysaccharides/toxicity ; Male ; Maternal Nutritional Physiological Phenomena ; MicroRNAs/genetics ; MicroRNAs/metabolism ; NF-E2-Related Factor 2/genetics ; NF-E2-Related Factor 2/metabolism ; Protective Agents/pharmacology ; Rats ; Rats, Sprague-Dawley ; Spirulina ; Up-Regulation ; p38 Mitogen-Activated Protein Kinases/genetics ; p38 Mitogen-Activated Protein Kinases/metabolism
    Chemical Substances Antioxidants ; Histones ; Interleukin-1beta ; Lipopolysaccharides ; MIRN146 microRNA, rat ; MicroRNAs ; NF-E2-Related Factor 2 ; Nfe2l2 protein, rat ; Protective Agents ; p38 Mitogen-Activated Protein Kinases (EC 2.7.11.24)
    Language English
    Publishing date 2016-08-29
    Publishing country England
    Document type Journal Article
    ZDB-ID 1447449-9
    ISSN 1476-8305 ; 1028-415X
    ISSN (online) 1476-8305
    ISSN 1028-415X
    DOI 10.1080/1028415X.2016.1221496
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Sustained Effects of Neonatal Systemic Lipopolysaccharide on IL-1β and Nrf2 in Adult Rat Substantia Nigra Are Partly Normalized by a Spirulina-Enriched Diet.

    Patil, Jaspal / Matte, Ashok / Nissbrandt, Hans / Mallard, Carina / Sandberg, Mats

    Neuroimmunomodulation

    2016  Volume 23, Issue 4, Page(s) 250–259

    Abstract: Background/aim: Neonatal infection can sensitize the adult substantia nigra (SN) to secondary insults, causing a decrease in antioxidant capacity which may lead to Parkinson's disease in adults. We studied the prolonged effect of systemic infection by ( ... ...

    Abstract Background/aim: Neonatal infection can sensitize the adult substantia nigra (SN) to secondary insults, causing a decrease in antioxidant capacity which may lead to Parkinson's disease in adults. We studied the prolonged effect of systemic infection by (i.p.) administration of lipopolysaccharide (LPS) on interleukin (IL)-1β, the antioxidant regulator nuclear factor-erythroid 2-related factor 2 (Nrf2), and the peroxisome proliferator-activated receptor γ coactivator (PGC)-1α in rat SN.
    Method and results: Five-day-old rat pups were treated with LPS (i.p. 2 mg/kg). After 65 days, the mRNA level of IL-1β was significantly increased, in parallel with a decrease in that of the rate-limiting enzyme in glutathione synthesis, the γ-glutamylcysteine ligase catalytic subunit (γGCLc), Nrf2, and brain-derived neurotrophic factor (BDNF). Protein levels of γGCLc and Nrf2 were decreased while IL-1β protein was significantly increased. These LPS-induced long-term changes correlated with a decrease in phosphorylated (active) AKT (pAKT) and phosphorylated (inactive) GSK-3β (pGSK-3β). In another set of experiments, a 0.1% Spirulina-containing diet was given to lactating mothers 24 h before the LPS treatment of the pups. The Spirulina-supplemented diet decreased IL-1β protein expression in SN and elevated the mRNA level of γGCLc, Nrf2 protein, PGC-1α protein, and pAKT.
    Conclusion: Early-life infection can negatively affect Nrf2, pAKT, and pGSK-3β for a long time in SN. A diet enriched with antioxidant and anti-inflammatory phytochemicals can partly restore some, but not all, of the effects on the antioxidant defense, possibly via normalizing effects on pAKT.
    Language English
    Publishing date 2016
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1184368-8
    ISSN 1423-0216 ; 1021-7401
    ISSN (online) 1423-0216
    ISSN 1021-7401
    DOI 10.1159/000452714
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    Zs.A 3975: Show issues Location:
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  4. Article: Sustained Effects of Neonatal Systemic Lipopolysaccharide on IL-1β and Nrf2 in Adult Rat Substantia Nigra Are Partly Normalized by a ; -Enriched Diet

    Patil, Jaspal / Matte, Ashok / Nissbrandt, Hans / Mallard, Carina / Sandberg, Mats

    Neuroimmunomodulation

    2016  Volume 23, Issue 4, Page(s) 250–259

    Abstract: Background/Aim: Neonatal infection can sensitize the adult substantia nigra (SN) to secondary insults, causing a decrease in antioxidant capacity which may lead to Parkinson's disease in adults. We studied the prolonged effect of systemic infection by (i. ...

    Institution Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, and Departments of Physiology and Pharmacology, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden
    Abstract Background/Aim: Neonatal infection can sensitize the adult substantia nigra (SN) to secondary insults, causing a decrease in antioxidant capacity which may lead to Parkinson's disease in adults. We studied the prolonged effect of systemic infection by (i.p.) administration of lipopolysaccharide (LPS) on interleukin (IL)-1β, the antioxidant regulator nuclear factor-erythroid 2-related factor 2 (Nrf2), and the peroxisome proliferator-activated receptor γ coactivator (PGC)-1α in rat SN. Method and Results: Five-day-old rat pups were treated with LPS (i.p. 2 mg/kg). After 65 days, the mRNA level of IL-1β was significantly increased, in parallel with a decrease in that of the rate-limiting enzyme in glutathione synthesis, the γ-glutamylcysteine ligase catalytic subunit (γGCLc), Nrf2, and brain-derived neurotrophic factor (BDNF). Protein levels of γGCLc and Nrf2 were decreased while IL-1β protein was significantly increased. These LPS-induced long-term changes correlated with a decrease in phosphorylated (active) AKT (pAKT) and phosphorylated (inactive) GSK-3β (pGSK-3β). In another set of experiments, a 0.1% Spirulina-containing diet was given to lactating mothers 24 h before the LPS treatment of the pups. The Spirulina-supplemented diet decreased IL-1β protein expression in SN and elevated the mRNA level of γGCLc, Nrf2 protein, PGC-1α protein, and pAKT. Conclusion: Early-life infection can negatively affect Nrf2, pAKT, and pGSK-3β for a long time in SN. A diet enriched with antioxidant and anti-inflammatory phytochemicals can partly restore some, but not all, of the effects on the antioxidant defense, possibly via normalizing effects on pAKT.
    Keywords Neuroinflammation ; Nrf2 ; Antioxidant system
    Language English
    Publishing date 2016-12-09
    Publisher S. Karger AG
    Publishing place Basel, Switzerland
    Document type Article
    Note Original Paper
    ZDB-ID 1184368-8
    ISSN 1423-0216 ; 1021-7401
    ISSN (online) 1423-0216
    ISSN 1021-7401
    DOI 10.1159/000452714
    Database Karger publisher's database

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    Zs.A 3975: Show issues Location:
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  5. Article ; Online: Time-dependent effects of systemic lipopolysaccharide injection on regulators of antioxidant defence Nrf2 and PGC-1α in the neonatal rat brain.

    Correa, Fernando / Ljunggren, Elin / Patil, Jaspal / Wang, Xiaoyang / Hagberg, Henrik / Mallard, Carina / Sandberg, Mats

    Neuroimmunomodulation

    2013  Volume 20, Issue 4, Page(s) 185–193

    Abstract: Background/aims: Both excitotoxicity and neuroinflammation are associated with oxidative stress. One transcription factor, nuclear factor E2-related factor 2 (Nrf2), and one transcription cofactor, peroxisome proliferator-activated receptor-γ ... ...

    Abstract Background/aims: Both excitotoxicity and neuroinflammation are associated with oxidative stress. One transcription factor, nuclear factor E2-related factor 2 (Nrf2), and one transcription cofactor, peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), increase the endogenous antioxidant defence and can thus modulate neuronal cell death. Here, we investigated the temporal effects (after 24 and 72 h) of systemic (i.p.) administration of lipopolysaccharide (LPS) on the cerebral Nrf2 and PGC-1α systems.
    Methods and results: Seven-day-old rat pups were injected with LPS (0.3 mg/kg). After 24 h, the protein levels of γ-glutamylcysteine ligase modulatory subunit, γ-glutamylcysteine ligase catalytic subunit, Nrf2, PGC-1α and manganese superoxide dismutase (MnSOD) were increased in parallel with decreased levels of Keap1. These effects were correlated with an increased level of phosphorylated Akt and elevated acetylation of histone 4. In contrast, 72 h following LPS, a decrease in the components of the Nrf2 system in parallel with an increase in Keap1 was observed. The down-regulation after 72 h correlated with phosphorylation of p38 mitogen-activated protein kinase, while there were no changes in PGC-1α and MnSOD protein levels or the acetylation/methylation pattern of histones.
    Conclusion: Systemic LPS in neonatal rats induced time-dependent changes in brain Nrf2 and PGC-1α that correlated well with the protective effect observed after 24 h (pre-conditioning) and the deleterious effects observed after 72 h (sensitizing) of systemic LPS reported earlier. Collectively, the results point towards Nrf2 and PGC-1α as a possible mechanism behind these effects.
    MeSH term(s) Animals ; Animals, Newborn ; Antioxidants/metabolism ; Brain/drug effects ; Brain/metabolism ; Brain/pathology ; Inflammation/chemically induced ; Inflammation/metabolism ; Inflammation/pathology ; Injections, Intraperitoneal ; Lipopolysaccharides/administration & dosage ; Lipopolysaccharides/toxicity ; NF-E2-Related Factor 2/biosynthesis ; Oxidative Stress/drug effects ; Oxidative Stress/physiology ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; Rats ; Rats, Sprague-Dawley ; Time Factors ; Transcription Factors/biosynthesis
    Chemical Substances Antioxidants ; Lipopolysaccharides ; NF-E2-Related Factor 2 ; Nfe2l2 protein, rat ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; Ppargc1a protein, rat ; Transcription Factors
    Language English
    Publishing date 2013-04-27
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1184368-8
    ISSN 1423-0216 ; 1021-7401
    ISSN (online) 1423-0216
    ISSN 1021-7401
    DOI 10.1159/000347161
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: NRF2-regulation in brain health and disease: implication of cerebral inflammation.

    Sandberg, Mats / Patil, Jaspal / D'Angelo, Barbara / Weber, Stephen G / Mallard, Carina

    Neuropharmacology

    2013  Volume 79, Page(s) 298–306

    Abstract: The nuclear factor erythroid 2 related factor 2 (NRF2) is a key regulator of endogenous inducible defense systems in the body. Under physiological conditions NRF2 is mainly located in the cytoplasm. However, in response to oxidative stress, NRF2 ... ...

    Abstract The nuclear factor erythroid 2 related factor 2 (NRF2) is a key regulator of endogenous inducible defense systems in the body. Under physiological conditions NRF2 is mainly located in the cytoplasm. However, in response to oxidative stress, NRF2 translocates to the nucleus and binds to specific DNA sites termed "anti-oxidant response elements" or "electrophile response elements" to initiate transcription of cytoprotective genes. Acute oxidative stress to the brain, such as stroke and traumatic brain injury is increased in animals that are deficient in NRF2. Insufficient NRF2 activation in humans has been linked to chronic diseases such as Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis. New findings have also linked activation of the NRF2 system to anti-inflammatory effects via interactions with NF-κB. Here we review literature on cellular mechanisms of NRF2 regulation, how to maintain and restore NRF2 function and the relationship between NRF2 regulation and brain damage. We bring forward the hypothesis that inflammation via prolonged activation of key kinases (p38 and GSK-3β) and activation of histone deacetylases gives rise to dysregulation of the NRF2 system in the brain, which contributes to oxidative stress and injury.
    MeSH term(s) Animals ; Brain/immunology ; Brain/physiology ; Brain/physiopathology ; Humans ; Inflammation/metabolism ; NF-E2-Related Factor 2/metabolism ; Signal Transduction/immunology ; Signal Transduction/physiology
    Chemical Substances NF-E2-Related Factor 2
    Language English
    Publishing date 2013-11-19
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 218272-5
    ISSN 1873-7064 ; 0028-3908
    ISSN (online) 1873-7064
    ISSN 0028-3908
    DOI 10.1016/j.neuropharm.2013.11.004
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    Ui I Zs.242: Show issues Location:
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  7. Article ; Online: Angiotensinergic innervation of the kidney: Localization and relationship with catecholaminergic postganglionic and sensory nerve fibers.

    Bohlender, Jürgen / Pfarrer, Beat / Patil, Jaspal / Nussberger, Jürg / Thalmann, Georg N / Imboden, Hans

    Histology and histopathology

    2012  Volume 27, Issue 11, Page(s) 1413–1428

    Abstract: We describe an angiotensin (Ang) II-containing innervation of the kidney. Cryosections of rat, pig and human kidneys were investigated for the presence of Ang II-containing nerve fibers using a mouse monoclonal antibody against Ang II (4B3). Co-staining ... ...

    Abstract We describe an angiotensin (Ang) II-containing innervation of the kidney. Cryosections of rat, pig and human kidneys were investigated for the presence of Ang II-containing nerve fibers using a mouse monoclonal antibody against Ang II (4B3). Co-staining was performed with antibodies against synaptophysin, tyrosine 3-hydroxylase, and dopamine beta-hydroxylase to detect catecholaminergic efferent fibers and against calcitonin gene-related peptide to detect sensory fibers. Tagged secondary antibodies and confocal light or laser scanning microscopy were used for immunofluorescence detection. Ang II-containing nerve fibers were densely present in the renal pelvis, the subepithelial layer of the urothelium, the arterial nervous plexus, and the peritubular interstitium of the cortex and outer medulla. They were infrequent in central veins and the renal capsule and absent within glomeruli and the renal papilla. Ang II-positive fibers represented phenotypic subgroups of catecholaminergic postganglionic or sensory fibers with different morphology and intrarenal distribution compared to their Ang II-negative counterparts. The Ang II-positive postganglionic fibers were thicker, produced typically fusiform varicosities and preferentially innervated the outer medulla and periglomerular arterioles. Ang II-negative sensory fibers were highly varicose, prevailing in the pelvis and scarce in the renal periphery compared to the rarely varicose Ang II-positive fibers. Neurons within renal microganglia displayed angiotensinergic, catecholaminergic, or combined phenotypes. Our results suggest that autonomic fibers may be an independent source of intrarenal Ang II acting as a neuropeptide co-transmitter or neuromodulator. The angiotensinergic renal innervation may play a distinct role in the neuronal control of renal sodium reabsorption, vasomotion and renin secretion.
    MeSH term(s) Angiotensin II/metabolism ; Animals ; Autonomic Nervous System/metabolism ; Humans ; Kidney/innervation ; Kidney/metabolism ; Male ; Nerve Fibers/metabolism ; Neurons/metabolism ; Rats ; Rats, Inbred WKY ; Swine ; Urothelium/metabolism
    Chemical Substances Angiotensin II (11128-99-7)
    Language English
    Publishing date 2012
    Publishing country Spain
    Document type Journal Article
    ZDB-ID 83911-5
    ISSN 1699-5848 ; 0213-3911
    ISSN (online) 1699-5848
    ISSN 0213-3911
    DOI 10.14670/HH-27.1413
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.B 3013: Show issues Location:
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  8. Article ; Online: Angiotensinergic and noradrenergic neurons in the rat and human heart.

    Patil, Jaspal / Stucki, Silvan / Nussberger, Juerg / Schaffner, Thomas / Gygax, Susanne / Bohlender, Juergen / Imboden, Hans

    Regulatory peptides

    2011  Volume 167, Issue 1, Page(s) 31–41

    Abstract: Although the physiological and pharmacological evidences suggest a role for angiotensin II (Ang II) with the mammalian heart, the source and precise location of Ang II are unknown. To visualize and quantitate Ang II in atria, ventricular walls and ... ...

    Abstract Although the physiological and pharmacological evidences suggest a role for angiotensin II (Ang II) with the mammalian heart, the source and precise location of Ang II are unknown. To visualize and quantitate Ang II in atria, ventricular walls and interventricular septum of the rat and human heart and to explore the feasibility of local Ang II production and function, we investigated by different methods the expression of proteins involved in the generation and function of Ang II. We found mRNA of angiotensinogen (Ang-N), of angiotensin converting enzyme, of the angiotensin type receptors AT(1A) and AT₂ (AT(1B) not detected) as well as of cathepsin D in any part of the hearts. No renin mRNA was traceable. Ang-N mRNA was visualized by in situ hybridization in atrial ganglial neurons. Ang II and dopamine-β-hydroxylase (DβH) were either colocalized inside the same neuronal cell or the neurons were specialized for Ang II or DβH. Within these neurons, the vesicular acetylcholine transporter (VAChT) was neither colocalized with Ang II nor DβH, but VAChT-staining was found with synapses en passant encircle these neuronal cells. The fibers containing Ang II exhibited with blood vessels and with cardiomyocytes supposedly angiotensinergic synapses en passant. In rat heart, right atrial median Ang II concentration appeared higher than septal and ventricular Ang II. The distinct colocalization of neuronal Ang II with DβH in the heart may indicate that Ang II participates together with norepinephrine in the regulation of cardiac functions: produced as a cardiac neurotransmitter Ang II may have inotropic, chronotropic or dromotropic effects in atria and ventricles and contributes to blood pressure regulation.
    MeSH term(s) Aged ; Aged, 80 and over ; Angiotensin II/genetics ; Angiotensin II/metabolism ; Angiotensinogen/genetics ; Angiotensinogen/metabolism ; Animals ; Blood Pressure/physiology ; Cathepsin D/genetics ; Cathepsin D/metabolism ; Dopamine beta-Hydroxylase/genetics ; Dopamine beta-Hydroxylase/metabolism ; Female ; Gene Expression ; Heart Atria/metabolism ; Heart Atria/ultrastructure ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Male ; Middle Aged ; Neurons/physiology ; Neurons/ultrastructure ; Neurotransmitter Agents/genetics ; Neurotransmitter Agents/metabolism ; Norepinephrine/metabolism ; RNA, Messenger/analysis ; Rats ; Rats, Inbred WKY ; Receptors, Angiotensin/genetics ; Receptors, Angiotensin/metabolism ; Synapses/physiology ; Synapses/ultrastructure ; Ventricular Septum/physiology ; Ventricular Septum/ultrastructure ; Vesicular Acetylcholine Transport Proteins/genetics ; Vesicular Acetylcholine Transport Proteins/metabolism
    Chemical Substances Neurotransmitter Agents ; RNA, Messenger ; Receptors, Angiotensin ; Vesicular Acetylcholine Transport Proteins ; Angiotensinogen (11002-13-4) ; Angiotensin II (11128-99-7) ; Dopamine beta-Hydroxylase (EC 1.14.17.1) ; Cathepsin D (EC 3.4.23.5) ; Norepinephrine (X4W3ENH1CV)
    Language English
    Publishing date 2011-02-25
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 225685-x
    ISSN 1873-1686 ; 0167-0115
    ISSN (online) 1873-1686
    ISSN 0167-0115
    DOI 10.1016/j.regpep.2010.11.011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 1593: Show issues Location:
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  9. Article: Angiotensinergic neurons in sympathetic coeliac ganglia innervating rat and human mesenteric resistance blood vessels.

    Patil, Jaspal / Heiniger, Eva / Schaffner, Thomas / Mühlemann, Oliver / Imboden, Hans

    Regulatory peptides

    2008  Volume 147, Issue 1-3, Page(s) 82–87

    Abstract: In contrast to the current belief that angiotensin II (Ang II) interacts with the sympathetic nervous system only as a circulating hormone, we document here the existence of endogenous Ang II in the neurons of rat and human sympathetic coeliac ganglia ... ...

    Abstract In contrast to the current belief that angiotensin II (Ang II) interacts with the sympathetic nervous system only as a circulating hormone, we document here the existence of endogenous Ang II in the neurons of rat and human sympathetic coeliac ganglia and their angiotensinergic innervation with mesenteric resistance blood vessels. Angiotensinogen - and angiotensin converting enzyme-mRNA were detected by using quantitative real time polymerase chain reaction in total RNA extracts of rat coeliac ganglia, while renin mRNA was untraceable. Cathepsin D, a protease responsible for cleavage beneath other substrates also angiotensinogen to angiotensin I, was successfully detected in rat coeliac ganglia indicating the possibility of existence of alternative pathways. Angiotensinogen mRNA was also detected by in situ hybridization in the cytoplasm of neurons of rat coeliac ganglia. Immunoreactivity for Ang II was demonstrated in rat and human coeliac ganglia as well as with mesenteric resistance blood vessels. By using confocal laser scanning microscopy we were able to demonstrate the presence of angiotensinergic synapses en passant along side of vascular smooth muscle cells. Our findings indicate that Ang II is synthesized inside the neurons of sympathetic coeliac ganglia and may act as an endogenous neurotransmitter locally with the mesenteric resistance blood vessels.
    MeSH term(s) Angiotensinogen/genetics ; Angiotensinogen/metabolism ; Animals ; Ganglia, Sympathetic/metabolism ; Humans ; Immunohistochemistry ; Male ; Mesenteric Arteries/innervation ; Neurons/metabolism ; RNA, Messenger/metabolism ; Rats ; Rats, Inbred WKY ; Renin-Angiotensin System/physiology ; Reverse Transcriptase Polymerase Chain Reaction
    Chemical Substances RNA, Messenger ; Angiotensinogen (11002-13-4)
    Language English
    Publishing date 2008-04-10
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 225685-x
    ISSN 1873-1686 ; 0167-0115
    ISSN (online) 1873-1686
    ISSN 0167-0115
    DOI 10.1016/j.regpep.2008.01.006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Intraneuronal angiotensinergic system in rat and human dorsal root ganglia.

    Patil, Jaspal / Schwab, Alexander / Nussberger, Juerg / Schaffner, Thomas / Saavedra, Juan M / Imboden, Hans

    Regulatory peptides

    2010  Volume 162, Issue 1-3, Page(s) 90–98

    Abstract: To elucidate the local formation of angiotensin II (Ang II) in the neurons of sensory dorsal root ganglia (DRG), we studied the expression of angiotensinogen (Ang-N)-, renin-, angiotensin converting enzyme (ACE)- and cathepsin D-mRNA, and the presence of ...

    Abstract To elucidate the local formation of angiotensin II (Ang II) in the neurons of sensory dorsal root ganglia (DRG), we studied the expression of angiotensinogen (Ang-N)-, renin-, angiotensin converting enzyme (ACE)- and cathepsin D-mRNA, and the presence of protein renin, Ang II, Substance P and calcitonin gene-related peptide (CGRP) in the rat and human thoracic DRG. Quantitative real time PCR (qRT-PCR) studies revealed that rat DRG expressed substantial amounts of Ang-N- and ACE mRNA, while renin mRNA as well as the protein renin were untraceable. Cathepsin D-mRNA and cathepsin D-protein were detected in the rat DRG indicating the possibility of existence of pathways alternative to renin for Ang I formation. Angiotensin peptides were successfully detected with high performance liquid chromatography and radioimmunoassay in human DRG extracts. In situ hybridization in rat DRG confirmed additionally expression of Ang-N mRNA in the cytoplasm of numerous neurons. Intracellular Ang II staining could be shown in number of neurons and their processes in both the rat and human DRG. Interestingly we observed neuronal processes with angiotensinergic synapses en passant, colocalized with synaptophysin, within the DRG. In the DRG, we also identified by qRT-PCR, expression of Ang II receptor AT(1A) and AT(2)-mRNA while AT(1B)-mRNA was not traceable. In some neurons Substance P and CGRP were found colocalized with Ang II. The intracellular localization and colocalization of Ang II with Substance P and CGRP in the DRG neurons may indicate a participation and function of Ang II in the regulation of nociception. In conclusion, these results suggest that Ang II may be produced locally in the neurons of rat and human DRG and act as a neurotransmitter.
    MeSH term(s) Angiotensinogen/genetics ; Angiotensins/metabolism ; Animals ; Base Sequence ; Cathepsin D/genetics ; Chromatography, High Pressure Liquid ; DNA Primers ; Ganglia, Spinal/metabolism ; Humans ; Immunohistochemistry ; Male ; Neurons/metabolism ; Peptidyl-Dipeptidase A/genetics ; RNA, Messenger/genetics ; Rats ; Rats, Inbred WKY ; Reverse Transcriptase Polymerase Chain Reaction
    Chemical Substances Angiotensins ; DNA Primers ; RNA, Messenger ; Angiotensinogen (11002-13-4) ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; Cathepsin D (EC 3.4.23.5)
    Language English
    Publishing date 2010-03-24
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 225685-x
    ISSN 1873-1686 ; 0167-0115
    ISSN (online) 1873-1686
    ISSN 0167-0115
    DOI 10.1016/j.regpep.2010.03.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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