Nitric oxide regulates AKT phosphorylation and nuclear translocation in cultured retinal cells

Mejía-García, Telmo A.; Portugal, Camila C.; Encarnação, Thaísa Godinho da; Prado, Marco A. M.; Paes‐de‐Carvalho, Roberto

doi:10.1016/j.cellsig.2013.08.001

Cited by 47 publications

(38 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, in E8 cultures, L-arginine treatment has already been described to increase endogenous NO production in an nNOS-dependent manner. 14,22 Interestingly, L-arginine administration promoted robust dose-dependent neuronal death in E6 purified cultures (Figure 2c) but it increased the viability of cultured E8 neurons (Figure 2e). Similarly, inhibiting basal NOS activity with L-NAME increased the viability of E6 neurons ( Figure 2d) and promoted neuronal death in cultured E8 neurons (Figure 2f).…”

Section: Resultsmentioning

confidence: 98%

“…44,45 Furthermore, it has been reported that NO regulates AKT activation and nuclear translocation via cGKII in retinal neurons. 22 We then decided to evaluate the role played by AKT in CREB phosphorylation regulated by cGKII in the nuclei. Knocking down cGKII with shRNAs was sufficient to increase nuclear phospho-AKT accumulation in E6 markedly (Figure 7a).…”

Section: Resultsmentioning

confidence: 99%

“…Antibodies. Primary antibodies: mouse anti-CREB (#9197), mouse antiphospho-CREB Ser133 (#9196), rabbit anti-phospho-CREB Ser133 (#9191) were from Cell Signaling (Danvers, MA, USA) and their specificity for chick CREB has been described previously 23,27 ; rabbit anti-cGKII (ab110124) was from Abcam (Cambridge, MA, USA), rabbit anti-phospho-AKT Ser473 (#9271) was from Cell Signaling and the specificity of both antibodies in the chick was previously determined 22 ; rabbit anti-phospho-nNOS Ser1417 (07-544) was from Millipore (Merck/Millipore) and its specificity was previously determined. 15 Antibody labeling in chick retinal cells was re-validated (Supplementary Figure 1).…”

Section: Discussionmentioning

confidence: 99%

“…21 In the developing retina, cGKs have been associated with Src avian sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (Src)-induced neuronal apoptosis, 15 ascorbate transport 14 and cGKII, specifically, regulates V-Akt murine thymoma viral oncogene (AKT)/PKB activation. 22 In addition, cyclic AMPresponsive element-binding protein (CREB) phosphorylation in retinal cells is dependent on a cGK-mediated extracellular regulated kinase (ERK) activation, which directly correlates glutamate and NO pathway to nuclear CREB activity in the retina. 23 Therefore, NO-mediated cGK activation also regulates physiological events in developing retinal cells.…”

mentioning

confidence: 99%

See 3 more Smart Citations

The nitric oxide-cGKII system relays death and survival signals during embryonic retinal development via AKT-induced CREB1 activation

et al. 2014

View full text Add to dashboard Cite

During early neurogenesis, retinal neuronal cells display a conserved differentiation program in vertebrates. Previous studies established that nitric oxide (NO) and cGMP accumulation regulate essential events in retinal physiology. Here we used pharmacological and genetic loss-of-function to investigate the effects of NO and its downstream signaling pathway in the survival of developing avian retinal neurons in vitro and in vivo. Six-day-old (E6) chick retinal cells displayed increased calcium influx and produced higher amounts of NO when compared with E8 cells. L-arginine (substrate for NO biosynthesis) and S-nitroso-N-acetyl-D,L-penicillamine (SNAP; a nitrosothiol NO donor) promoted extensive cell death in E6 retinas, whereas in E8 both substances decreased apoptosis. The effect of NO at both periods was mediated by soluble guanylyl cyclase (sGC) and cGMP-dependent kinase (cGK) activation. In addition, shRNA-mediated cGKII knockdown prevented NO-induced cell death (E6) and cell survival (E8). This, NO-induced cell death or cell survival was not correlated with an early inhibition of retinal cell proliferation. E6 cells also responded differentially from E8 neurons regarding cyclic AMP-responsive element-binding protein (CREB) activation in the retina in vivo. NO strongly decreased nuclear phospho-CREB staining in E6 but it robustly enhanced CREB phosphorylation in the nuclei of E8 neurons, an effect that was completely abrogated by cGKII shRNAs at both embryonic stages. The ability of NO in regulating CREB differentially during retinal development relied on the capacity of cGKII in decreasing (E6) or increasing (E8) nuclear AKT (V-Akt murine thymoma viral oncogene) activation. Accordingly, inhibiting AKT prevented both cGKII shRNA-mediated CREB upregulation in E6 and SNAP-induced CREB activation in E8. Furthermore, shRNAmediated in vivo cGKII or in vitro CREB1 knockdown confirmed that NO/cGKII dualistically regulated the downstream CREB1 pathway and caspase activation in the chick retina to modulate neuronal viability. These data demonstrate that NO-mediated cGKII signaling may function to control the viability of neuronal cells during early retinal development via AKT/CREB1 activity. Cell Death and Differentiation (2014) 21, 915-928; doi:10.1038/cdd.2014.11; published online 14 February 2014The retina is part of the central nervous system (CNS) because of its derivation from the anterior neural tube. Mature retinal tissue is arranged in a laminar structure composed of seven major classes of cells: ganglion, horizontal, amacrine, bipolar, cone and rod photoreceptors and the Mü ller glia. 1 Early retinal tissue is a pseudo-stratified epithelium in which mitotically active neuronal precursor cells are found. Another noteworthy characteristic of vertebrate retinogenesis is the well-established chronology of cell-type generation, with ganglion cells generally being the first cells to be born and the Mü ller glia and bipolar neurons usually the last. Nevertheless, the differentiation periods of different cell type...

show abstract

Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

The nitric oxide-cGKII system relays death and survival signals during embryonic retinal development via AKT-induced CREB1 activation

et al. 2014

View full text Add to dashboard Cite

show abstract

“…In cultured chick embryonic retinal neurons, both endogenous and exogenous NO promoted AKT signalling pathway and probably survival mechanisms [37]. In goldfish optic nerve, scientists showed that NO signalling pathway through nNOS activation has a crucial role in nerve regeneration [38].…”

Section: Roles Of Noss In Seeing and Retinal Functionmentioning

confidence: 99%

Role of Nitric Oxide Synthase in Normal Brain Function and Pathophysiology of Neural Diseases

Dagdeviren¹

2017

Nitric Oxide Synthase - Simple Enzyme-Complex Roles

View full text Add to dashboard Cite

Nitric oxide synthase has three isoforms; according to their roles and tissues or cells they are involved. Neuronal NOS (nNOS) takes place in neuronal signalling, endothelial NOS (eNOS) takes place in vasodilation and inducible NOS (iNOS) takes place in immune responses. nNOS and eNOS are dominant but all isoforms have various roles in the central nervous system. nNOS and eNOS separately or together works in healthy brain during cognitive processes and in unhealthy brain during the pathology of related diseases. These roles were shown by inhibitor applied or by transgenic animal model studies and also by investigating the diseases at the molecular level. Besides, it is possible to say that iNOS has roles in some neurological pathologies creating immune responses. Three different isoforms mainly serve in different systems so there are lots of researchers from various disciplines working collaterally not knowing the others related works about NOSs. Because of this, a comprehensive chapter will be valuable for neuroscientists working with either healthy or unhealthy brains. The purpose of this chapter is to gather an overview of NOSs duties during the normal processes of the brain like learning and memory formation and abnormal processes such as depression, schizophrenia and brain cancers.

show abstract

A beneficial role for elevated extracellular glutamate in Amyotrophic Lateral Sclerosis and cerebral ischemia

Schiel

2021

BioEssays

View full text Add to dashboard Cite

This hypothesis proposes that increased extracellular glutamate in Amyotrophic Lateral Sclerosis (ALS) and cerebral ischemia, currently viewed as a trigger for excitotoxicity, is actually beneficial as it stimulates the utilization of glutamate as metabolic fuel.Renewed appreciation of glutamate oxidation by ischemic neurons has raised questions regarding the role of extracellular glutamate in ischemia. Is it detrimental, as suggested by excitotoxicity in early in vitro studies, or beneficial, as suggested by its oxidation in later in vivo studies? The answer may depend on the activity of N-methyl-Daspartate (NMDA) glutamate receptors. Early in vitro procedures co-activated NMDA receptors (NMDARs) containing 2A (GluN2A) and 2B (GluN2B) subunits, an event now believed to trigger excitotoxicity; however, during in vivo ischemia D-serine and zinc molecules are released and these ensure only GluN2B receptors are stimulated. This not only prevents excitotoxicity but also initiates signaling cascades that allow ischemic neurons to import and oxidize glutamate.

show abstract

Nitric oxide regulates AKT phosphorylation and nuclear translocation in cultured retinal cells

Cited by 47 publications

References 61 publications

The nitric oxide-cGKII system relays death and survival signals during embryonic retinal development via AKT-induced CREB1 activation

The nitric oxide-cGKII system relays death and survival signals during embryonic retinal development via AKT-induced CREB1 activation

Role of Nitric Oxide Synthase in Normal Brain Function and Pathophysiology of Neural Diseases

A beneficial role for elevated extracellular glutamate in Amyotrophic Lateral Sclerosis and cerebral ischemia

Contact Info

Product

Resources

About