scholarly journals Chemotactic Peptide-induced Changes of Intermediate Filament Organization in Neutrophils during Granule Secretion: Role of Cyclic Guanosine Monophosphate

1998 ◽  
Vol 9 (10) ◽  
pp. 2933-2947 ◽  
Author(s):  
Katherine B. Pryzwansky ◽  
Elizabeth P. Merricks
Keyword(s):  
Intermediate Filaments ◽  
Intermediate Filament ◽  
Cyclic Guanosine Monophosphate ◽  
Cytochalasin D ◽  
Guanosine Monophosphate ◽  
Microtubule Organization ◽  
Intact Cells ◽  
Filament Assembly ◽  
Dependent Protein ◽  
Granule Secretion

In neutrophils activated to secrete with formyl-methionyl-leucyl-phenylalanine, intermediate filaments are phosphorylated transiently by cyclic guanosine monophosphate (cGMP)-dependent protein kinase (G-kinase). cGMP regulation of vimentin organization was investigated. During granule secretion, cGMP levels were elevated and intermediate filaments were transiently assembled at the pericortex to areas devoid of granules and microfilaments. Microtubule and microfilament inhibitors affected intermediate filament organization, granule secretion, and cGMP levels. Cytochalasin D and nocodazole caused intermediate filaments to assemble at the nucleus, rather than at the pericortex. cGMP levels were elevated in neutrophils by both inhibitors; however, with cytochalasin D, cGMP was elevated earlier and granule secretion was excessive. Nocodazole did not affect normal cGMP elevations, but specific granule secretion was delayed. LY83583, a guanylyl cyclase antagonist, inhibited granule secretion and intermediate filament organization, but not microtubule or microfilament organization. Intermediate filament assembly at the pericortex and secretion were partially restored by 8-bromo-cGMP in LY83583-treated neutrophils, suggesting that cGMP regulates these functions. G-kinase directly induced intermediate filament assembly in situ, and protein phosphatase 1 disassembled filaments. However, in intact cells stimulated with formyl-methionyl-leucyl-phenylalanine, intermediate filament assembly is focal and transient, suggesting that vimentin phosphorylation is compartmentalized. We propose that, in addition to changes in microfilament and microtubule organization, granule secretion is also accompanied by changes in intermediate filament organization, and that cGMP regulates vimentin filament organization via activation of G-kinase.

scholarly journals The cGMP-Dependent Protein Kinase 2 Contributes to Cone Photoreceptor Degeneration in the Cnga3-Deficient Mouse Model of Achromatopsia

2020 ◽  
Vol 22 (1) ◽  
pp. 52
Author(s):  
Mirja Koch ◽  
Constanze Scheel ◽  
Hongwei Ma ◽  
Fan Yang ◽  
Michael Stadlmeier ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Mouse Model ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Cone Photoreceptor ◽  
Photoreceptor Degeneration ◽  
Dependent Protein Kinase ◽  
Genetic Ablation ◽  
Cgmp Dependent Protein Kinase ◽  
Dependent Protein

Mutations in the CNGA3 gene, which encodes the A subunit of the cyclic guanosine monophosphate (cGMP)-gated cation channel in cone photoreceptor outer segments, cause total colour blindness, also referred to as achromatopsia. Cones lacking this channel protein are non-functional, accumulate high levels of the second messenger cGMP and degenerate over time after induction of ER stress. The cell death mechanisms that lead to loss of affected cones are only partially understood. Here, we explored the disease mechanisms in the Cnga3 knockout (KO) mouse model of achromatopsia. We found that another important effector of cGMP, the cGMP-dependent protein kinase 2 (Prkg2) is crucially involved in cGMP cytotoxicity of cones in Cnga3 KO mice. Virus-mediated knockdown or genetic ablation of Prkg2 in Cnga3 KO mice counteracted degeneration and preserved the number of cones. Analysis of markers of endoplasmic reticulum stress and unfolded protein response confirmed that induction of these processes in Cnga3 KO cones also depends on Prkg2. In conclusion, we identified Prkg2 as a novel key mediator of cone photoreceptor degeneration in achromatopsia. Our data suggest that this cGMP mediator could be a novel pharmacological target for future neuroprotective therapies.

scholarly journals ANP and BNP Exert Anti-Inflammatory Action via NPR-1/cGMP Axis by Interfering with Canonical, Non-Canonical, and Alternative Routes of Inflammasome Activation in Human THP1 Cells

2020 ◽  
Vol 22 (1) ◽  
pp. 24
Author(s):  
Letizia Mezzasoma ◽  
Vincenzo Nicola Talesa ◽  
Rita Romani ◽  
Ilaria Bellezza
Keyword(s):  
Natriuretic Peptide ◽  
Specific Inhibitor ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Caspase 8 ◽  
Inflammasome Activation ◽  
Intracellular Cgmp ◽  
Dependent Protein ◽  
Anti Inflammatory ◽  
Alternative Routes

Dysregulated inflammasome activation and interleukin (IL)-1β production are associated with several inflammatory disorders. Three different routes can lead to inflammasome activation: a canonical two-step, a non-canonical Caspase-4/5- and Gasdermin D-dependent, and an alternative Caspase-8-mediated pathway. Natriuretic Peptides (NPs), Atrial Natriuretic Peptide (ANP) and B-type Natriuretic Peptide (BNP), binding to Natriuretic Peptide Receptor-1 (NPR-1), signal by increasing cGMP (cyclic guanosine monophosphate) levels that, in turn, stimulate cGMP-dependent protein kinase-I (PKG-I). We previously demonstrated that, by counteracting inflammasome activation, NPs inhibit IL-1β secretion. Here we aimed to decipher the molecular mechanism underlying NPs effects on THP-1 cells stimulated with lipopolysaccharide (LPS) + ATP. Involvement of cGMP and PKG-I were assessed pre-treating THP-1 cells with the membrane-permeable analogue, 8-Br-cGMP, and the specific inhibitor KT-5823, respectively. We found that NPs, by activating NPR-1/cGMP/PKG-I axis, lead to phosphorylation of NLRP3 at Ser295 and to inflammasome platform disassembly. Moreover, by increasing intracellular cGMP levels and activating phosphodiesterases, NPs interfere with both Gasdermin D and Caspase-8 cleavage, indicating that they disturb non-canonical and alternative routes of inflammasome activation. These results showed that ANP and BNP anti-inflammatory and immunomodulatory actions may involve the inhibition of all the known routes of inflammasome activation. Thus, NPs might be proposed for the treatment of the plethora of diseases caused by a dysregulated inflammasome activation.

The cGMP system: components and function

2020 ◽  
Vol 401 (4) ◽  
pp. 447-469 ◽  
Author(s):  
Franz Hofmann
Keyword(s):  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Signaling System ◽  
Pde Inhibitors ◽  
Mammalian Tissues ◽  
System Components ◽  
Cgmp Signaling ◽  
Dependent Protein ◽  
Successful Approach ◽  
And Function

AbstractThe cyclic guanosine monophosphate (cGMP) signaling system is one of the most prominent regulators of a variety of physiological and pathophysiological processes in many mammalian and non-mammalian tissues. Targeting this pathway by increasing cGMP levels has been a very successful approach in pharmacology as shown for nitrates, phosphodiesterase (PDE) inhibitors and stimulators of nitric oxide-guanylyl cyclase (NO-GC) and particulate GC (pGC). This is an introductory review to the cGMP signaling system intended to introduce those readers to this system, who do not work in this area. This article does not intend an in-depth review of this system. Signal transduction by cGMP is controlled by the generating enzymes GCs, the degrading enzymes PDEs and the cGMP-regulated enzymes cyclic nucleotide-gated ion channels, cGMP-dependent protein kinases and cGMP-regulated PDEs. Part A gives a very concise introduction to the components. Part B gives a very concise introduction to the functions modulated by cGMP. The article cites many recent reviews for those who want a deeper insight.

scholarly journals alpha-Internexin, a 66-kD intermediate filament-binding protein from mammalian central nervous tissues.

1985 ◽  
Vol 101 (4) ◽  
pp. 1316-1322 ◽  
Author(s):  
J S Pachter ◽  
R K Liem
Keyword(s):  
Optic Nerve ◽  
Intermediate Filaments ◽  
Intermediate Filament ◽  
Peptide Mapping ◽  
Exchange Chromatography ◽  
Filament Assembly ◽  
Antigen Antibody

In this paper we describe a 66-kD protein that co-purifies with intermediate filaments from rat optic nerve and spinal cord but can be separated further by ion-exchange chromatography. This protein is distinct from the 68-kD neurofilament subunit protein as judged by isoelectric focusing, immunoblotting, peptide mapping, and tests of polymerization competence. This protein is avidly recognized by the monoclonal anti-intermediate filament antigen antibody, previously demonstrated to recognize a common antigenic determinant in all five known classes of intermediate filaments. Also, when isolated this protein binds to various intermediate filament subunit proteins, which suggests an in vivo interaction with the intermediate filament cytoskeleton, and it appears to be axonally transported in the rat optic nerve. Because of this ability to bind to intermediate filaments in situ and in vitro we have named this protein alpha-internexin. A possible functional role for the protein in organizing filament assembly and distribution is discussed.

Sign in / Sign up

Export Citation Format

Share Document