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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2004
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00071188_v143_n8_p1058_Rosignoli http://hdl.handle.net/20.500.12110/paper_00071188_v143_n8_p1058_Rosignoli |
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paper:paper_00071188_v143_n8_p1058_Rosignoli2023-06-08T14:31:37Z Inhibition of calcium-calmodulin kinase restores nitric oxide production and signaling in submandibular glands of a mouse model of salivary dysfunction Rosignoli, Florencia Roca, Valeria Inés Pregi, Nicolás Pérez Leirós, Claudia 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. 2004 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00071188_v143_n8_p1058_Rosignoli 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, Florencia Roca, Valeria Inés Pregi, Nicolás Pérez Leirós, Claudia 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. |
| author |
Rosignoli, Florencia Roca, Valeria Inés Pregi, Nicolás Pérez Leirós, Claudia |
| author_facet |
Rosignoli, Florencia Roca, Valeria Inés Pregi, Nicolás Pérez Leirós, Claudia |
| author_sort |
Rosignoli, Florencia |
| 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 |
| publishDate |
2004 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00071188_v143_n8_p1058_Rosignoli http://hdl.handle.net/20.500.12110/paper_00071188_v143_n8_p1058_Rosignoli |
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