Inhibition of calcium-calmodulin kinase restores nitric oxide production and signaling in submandibular glands of a mouse model of salivary dysfunction

Nitric oxide is an intracellular and diffusible messenger of neurotransmitters involved in salivary secretion, as well as an inflammatory mediator in salivary gland diseases. It is synthesized by three different isoforms of nitric oxide synthase (NOS), each subject to a fine transcriptional, post-tr...

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Autores principales:	Rosignoli, F., Roca, V., Meiss, R., Pregi, N., Pérez Leirós, C.
Formato:	JOUR
Materias:	CaM kinase inhibition KN-93 NOD mice NOS regulation Salivary dysfunction arginase bisindolylmaleimide complementary DNA cyclic GMP glyceraldehyde 3 phosphate dehydrogenase messenger RNA n [2 [[n [3 (4 chlorophenyl) 2 propenyl] n methylamino]methyl]phenyl] n (2 hydroxyethyl) 4 methoxybenzenesulfonamide n(g) methylarginine nitric oxide nitric oxide synthase inhibitor protein kinase (calcium,calmodulin) protein kinase inhibitor animal model animal tissue article DNA synthesis down regulation enzyme assay enzyme inhibition immunohistochemistry mouse nonhuman priority journal protein expression reverse transcription polymerase chain reaction salivary gland signal transduction submandibular gland Western blotting Animals Ca(2+)-Calmodulin Dependent Protein Kinase Disease Models, Animal Female Mice Mice, Inbred BALB C Mice, Inbred NOD Nitric Oxide Protein Kinase Inhibitors Salivary Gland Diseases Signal Transduction Submandibular Gland
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_00071188_v143_n8_p1058_Rosignoli
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	todo:paper_00071188_v143_n8_p1058_Rosignoli2023-10-03T14:05:30Z Inhibition of calcium-calmodulin kinase restores nitric oxide production and signaling in submandibular glands of a mouse model of salivary dysfunction Rosignoli, F. Roca, V. Meiss, R. Pregi, N. Pérez Leirós, C. CaM kinase inhibition KN-93 NOD mice NOS regulation Salivary dysfunction arginase bisindolylmaleimide complementary DNA cyclic GMP glyceraldehyde 3 phosphate dehydrogenase messenger RNA n [2 [[n [3 (4 chlorophenyl) 2 propenyl] n methylamino]methyl]phenyl] n (2 hydroxyethyl) 4 methoxybenzenesulfonamide n(g) methylarginine nitric oxide nitric oxide synthase inhibitor protein kinase (calcium,calmodulin) protein kinase inhibitor animal model animal tissue article DNA synthesis down regulation enzyme assay enzyme inhibition immunohistochemistry mouse nonhuman priority journal protein expression reverse transcription polymerase chain reaction salivary gland signal transduction submandibular gland Western blotting Animals Ca(2+)-Calmodulin Dependent Protein Kinase Disease Models, Animal Female Mice Mice, Inbred BALB C Mice, Inbred NOD Nitric Oxide Protein Kinase Inhibitors Salivary Gland Diseases Signal Transduction Submandibular Gland Nitric oxide is an intracellular and diffusible messenger of neurotransmitters involved in salivary secretion, as well as an inflammatory mediator in salivary gland diseases. It is synthesized by three different isoforms of nitric oxide synthase (NOS), each subject to a fine transcriptional, post-transcriptional and/or post-translational regulation. Our purpose was to study the possible mechanisms leading to NOS downregulation in submandibular glands of normal mice and in the nonobese diabetic (NOD) mouse model of salivary dysfunction with lower NOS activity. NOS activity and cGMP accumulation were determined by radioassays in submandibular glands of both mice in the presence of the protein kinase inhibitors KN-93 and bisindolylmaleimide. NOS I mRNA and protein expression and localization were assessed by RT-PCR, Western blot and immunohistochemistry. A downregulatory effect of calcium-calmodulin kinase II (CaMK II) on NOS activity in submandibular glands of both NOD and BALB/c mice was observed. Our results are consistent with a physiological regulation of NOS activity by this kinase but not by PKC in normal BALB/c mice. They are also supportive of a role for CaMK II in the lack of detectable NOS activity in submandibular glands of NOD mice. KN-93 also restored cGMP accumulation in NOD submandibular glands. 4 The downregulation of NOS in NOD mice seems to be mainly mediated by this kinase rather than the result of a lower expression or different cellular localization of the enzyme. It was not related to different substrate or cofactors availability either. Fil:Rosignoli, F. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Roca, V. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Pregi, N. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Pérez Leirós, C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00071188_v143_n8_p1058_Rosignoli
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	CaM kinase inhibition KN-93 NOD mice NOS regulation Salivary dysfunction arginase bisindolylmaleimide complementary DNA cyclic GMP glyceraldehyde 3 phosphate dehydrogenase messenger RNA n [2 [[n [3 (4 chlorophenyl) 2 propenyl] n methylamino]methyl]phenyl] n (2 hydroxyethyl) 4 methoxybenzenesulfonamide n(g) methylarginine nitric oxide nitric oxide synthase inhibitor protein kinase (calcium,calmodulin) protein kinase inhibitor animal model animal tissue article DNA synthesis down regulation enzyme assay enzyme inhibition immunohistochemistry mouse nonhuman priority journal protein expression reverse transcription polymerase chain reaction salivary gland signal transduction submandibular gland Western blotting Animals Ca(2+)-Calmodulin Dependent Protein Kinase Disease Models, Animal Female Mice Mice, Inbred BALB C Mice, Inbred NOD Nitric Oxide Protein Kinase Inhibitors Salivary Gland Diseases Signal Transduction Submandibular Gland
spellingShingle	CaM kinase inhibition KN-93 NOD mice NOS regulation Salivary dysfunction arginase bisindolylmaleimide complementary DNA cyclic GMP glyceraldehyde 3 phosphate dehydrogenase messenger RNA n [2 [[n [3 (4 chlorophenyl) 2 propenyl] n methylamino]methyl]phenyl] n (2 hydroxyethyl) 4 methoxybenzenesulfonamide n(g) methylarginine nitric oxide nitric oxide synthase inhibitor protein kinase (calcium,calmodulin) protein kinase inhibitor animal model animal tissue article DNA synthesis down regulation enzyme assay enzyme inhibition immunohistochemistry mouse nonhuman priority journal protein expression reverse transcription polymerase chain reaction salivary gland signal transduction submandibular gland Western blotting Animals Ca(2+)-Calmodulin Dependent Protein Kinase Disease Models, Animal Female Mice Mice, Inbred BALB C Mice, Inbred NOD Nitric Oxide Protein Kinase Inhibitors Salivary Gland Diseases Signal Transduction Submandibular Gland Rosignoli, F. Roca, V. Meiss, R. Pregi, N. Pérez Leirós, C. Inhibition of calcium-calmodulin kinase restores nitric oxide production and signaling in submandibular glands of a mouse model of salivary dysfunction
topic_facet	CaM kinase inhibition KN-93 NOD mice NOS regulation Salivary dysfunction arginase bisindolylmaleimide complementary DNA cyclic GMP glyceraldehyde 3 phosphate dehydrogenase messenger RNA n [2 [[n [3 (4 chlorophenyl) 2 propenyl] n methylamino]methyl]phenyl] n (2 hydroxyethyl) 4 methoxybenzenesulfonamide n(g) methylarginine nitric oxide nitric oxide synthase inhibitor protein kinase (calcium,calmodulin) protein kinase inhibitor animal model animal tissue article DNA synthesis down regulation enzyme assay enzyme inhibition immunohistochemistry mouse nonhuman priority journal protein expression reverse transcription polymerase chain reaction salivary gland signal transduction submandibular gland Western blotting Animals Ca(2+)-Calmodulin Dependent Protein Kinase Disease Models, Animal Female Mice Mice, Inbred BALB C Mice, Inbred NOD Nitric Oxide Protein Kinase Inhibitors Salivary Gland Diseases Signal Transduction Submandibular Gland
description	Nitric oxide is an intracellular and diffusible messenger of neurotransmitters involved in salivary secretion, as well as an inflammatory mediator in salivary gland diseases. It is synthesized by three different isoforms of nitric oxide synthase (NOS), each subject to a fine transcriptional, post-transcriptional and/or post-translational regulation. Our purpose was to study the possible mechanisms leading to NOS downregulation in submandibular glands of normal mice and in the nonobese diabetic (NOD) mouse model of salivary dysfunction with lower NOS activity. NOS activity and cGMP accumulation were determined by radioassays in submandibular glands of both mice in the presence of the protein kinase inhibitors KN-93 and bisindolylmaleimide. NOS I mRNA and protein expression and localization were assessed by RT-PCR, Western blot and immunohistochemistry. A downregulatory effect of calcium-calmodulin kinase II (CaMK II) on NOS activity in submandibular glands of both NOD and BALB/c mice was observed. Our results are consistent with a physiological regulation of NOS activity by this kinase but not by PKC in normal BALB/c mice. They are also supportive of a role for CaMK II in the lack of detectable NOS activity in submandibular glands of NOD mice. KN-93 also restored cGMP accumulation in NOD submandibular glands. 4 The downregulation of NOS in NOD mice seems to be mainly mediated by this kinase rather than the result of a lower expression or different cellular localization of the enzyme. It was not related to different substrate or cofactors availability either.
format	JOUR
author	Rosignoli, F. Roca, V. Meiss, R. Pregi, N. Pérez Leirós, C.
author_facet	Rosignoli, F. Roca, V. Meiss, R. Pregi, N. Pérez Leirós, C.
author_sort	Rosignoli, F.
title	Inhibition of calcium-calmodulin kinase restores nitric oxide production and signaling in submandibular glands of a mouse model of salivary dysfunction
title_short	Inhibition of calcium-calmodulin kinase restores nitric oxide production and signaling in submandibular glands of a mouse model of salivary dysfunction
title_full	Inhibition of calcium-calmodulin kinase restores nitric oxide production and signaling in submandibular glands of a mouse model of salivary dysfunction
title_fullStr	Inhibition of calcium-calmodulin kinase restores nitric oxide production and signaling in submandibular glands of a mouse model of salivary dysfunction
title_full_unstemmed	Inhibition of calcium-calmodulin kinase restores nitric oxide production and signaling in submandibular glands of a mouse model of salivary dysfunction
title_sort	inhibition of calcium-calmodulin kinase restores nitric oxide production and signaling in submandibular glands of a mouse model of salivary dysfunction
url	http://hdl.handle.net/20.500.12110/paper_00071188_v143_n8_p1058_Rosignoli
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Inhibition of calcium-calmodulin kinase restores nitric oxide production and signaling in submandibular glands of a mouse model of salivary dysfunction

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