A Novel, Nongenomic Mechanism Underlies Retinoic Acid-Induced Growth Cone Turning

Farrar, Nathan; Dmetrichuk, Jennifer M.; Carlone, Robert L.; Spencer, Gaynor E.

doi:10.1523/jneurosci.2921-09.2009

Cited by 47 publications

(53 citation statements)

References 38 publications

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“…Using central neurons from adult animals, Farrar et al [165] showed that RA-induced positive growth cone turning was maintained even in the presence of actinomycin D, an inhibitor of transcription, thereby showing that this process is independent of transcription. This RA-dependent process requires local protein synthesis and Ca 2?…”

Section: Non-genomic Signalingmentioning

confidence: 99%

From carrot to clinic: an overview of the retinoic acid signaling pathway

Theodosiou

Laudet

Schubert

2010

Cell. Mol. Life Sci.

284

247

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Vitamin A is essential for the formation and maintenance of many body tissues. It is also important for embryonic growth and development and can act as a teratogen at critical periods of development. Retinoic acid (RA) is the biologically active form of vitamin A and its signaling is mediated by the RA and retinoid X receptors. In addition to its role as an important molecule during development, RA has also been implicated in clinical applications, both as a potential anti-tumor agent as well as for the treatment of skin diseases. This review presents an overview of how dietary retinoids are converted to RA, hence presenting the major players in RA metabolism and signaling, and highlights examples of treatment applications of retinoids. Moreover, we discuss the origin and diversification of the retinoid pathway, which are important factors for understanding the evolution of ligand-specificity among retinoid receptors.

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Section: Non-genomic Signalingmentioning

confidence: 99%

From carrot to clinic: an overview of the retinoic acid signaling pathway

Theodosiou

Laudet

Schubert

2010

Cell. Mol. Life Sci.

284

247

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“…RA has previously been shown to affect protein synthesis Chen 2008), PKA signaling (Kholodenko et al 2007) and PLC activation (Liou et al 2005). However, despite our use of pharmacological inhibitors that 1) are capable of blocking other effects of RA (Farrar et al 2009;Liou et al 2005) and 2) are known effective blockers in Lymnaea (Dobson et al 2006;Farrar et al 2009;Hamakawa et al 1999;Lacchini et al 2006;Marra et al 2013), there was no evidence to support a role for these particular pathways in the effects of atRA on neuronal firing. We did, however, find that acute exposure to atRA resulted in a significant decline in [Ca 2ϩ ] i as early as 15 min after application.…”

Section: Discussionmentioning

confidence: 88%

“…Vehicle controls for the retinoid antagonist experiments used 0.01% DMSO (final bath concentration). Anisomycin, used to block protein synthesis, was added for a final bath concentration of 45 M (Farrar et al 2009;Hamakawa et al 1999). The final bath concentration of the PKA inhibitors (PKAi), Rp-adenosine 3=,5=-cyclic monophosphorothioate (Rp-cAMPs) was 10 M and for H-89 was 5 M (Marra et al 2013).…”

Section: Methodsmentioning

confidence: 99%

“…The vitamin A metabolite, retinoic acid (RA), is also very important for development and regeneration of the nervous system (Maden 2007) and can induce neurite outgrowth (Clagett-Dame et al 2006;Corcoran et al 2000), promote growth cone turning Farrar et al 2009), as well as modulate hippocampal synaptic plasticity, such as long-term potentiation and depression (Chiang et al 1998;Misner et al 2001;Nomoto et al 2012). We recently investigated whether RA might exert some of its effects by directly modulating the electrical firing of neurons.…”

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confidence: 99%

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Retinoic acid affects calcium signaling in adult molluscan neurons

Vesprini

Dawson

Yuan

et al. 2015

Journal of Neurophysiology

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acid, the active metabolite of vitamin A, is important for nervous system development, regeneration, as well as cognitive functions of the adult central nervous system. These central nervous system functions are all highly dependent on neuronal activity. Retinoic acid has previously been shown to induce changes in the firing properties and action potential waveforms of adult molluscan neurons in a dose-and isomer-dependent manner. In this study, we aimed to determine the cellular pathways by which retinoic acid might exert such effects, by testing the involvement of pathways previously shown to be affected by retinoic acid. We demonstrated that the ability of all-trans retinoic acid (atRA) to induce electrophysiological changes in cultured molluscan neurons was not prevented by inhibitors of protein synthesis, protein kinase A or phospholipase C. However, we showed that atRA was capable of rapidly reducing intracellular calcium levels in the same dose-and isomer-dependent manner as shown previously for changes in neuronal firing. Moreover, we also demonstrated that the transmembrane ion flux through voltage-gated calcium channels was rapidly modulated by retinoic acid. In particular, the peak current density was reduced and the inactivation rate was increased in the presence of atRA, over a similar time course as the changes in cell firing and reductions in intracellular calcium. These studies provide further evidence for the ability of atRA to induce rapid effects in mature neurons.

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“…Given that our cultures were exposed to ATRA from times ranging from neuronal cell line [52], and the growth cone turning response in mollusc neurons in vitro [53].…”

Section: Discussionmentioning

confidence: 99%

Acute effects of all-trans-retinoic acid in ischemic injury

Panickar¹,

Dawson

2012

Translational Neuroscience

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All-trans-retinoic acid (ATRA) is a vitamin A derivative that is important in neuronal patterning, survival, and neurite outgrowth. Neuroprotective effects of ATRA in ischemia have been demonstrated but its effects on glial swelling are not known. We investigated the relatively acute effects of ATRA on cell swelling in ischemic injury and on key features hypothesized to contribute to cell swelling including increased reactive oxygen species/ reactive nitrogen species (ROS/RNS), depolarization of the inner mitochondrial membrane potential (ΔΨ m ), and increased intracellular calcium ([Ca 2+ ] i ). C6 glial cultures were subjected to 5 hr oxygen-glucose deprivation (OGD). ATRA was added to separate groups after the end of OGD. OGD increased cell volume by 43%, determined at 90 min after the end of OGD, but this increase was significantly attenuated by ATRA. OGD induced an increase in ROS/RNS production in the whole cell and mitochondria, as assessed by the fluorescent dyes CM-H 2 DCFDA and MitoTracker CM-H 2 -XROS at the end of OGD. The increase in mitochondrial ROS, but not cellular ROS, was significantly attenuated by ATRA. OGD also induced a 67% decline in mitochondrial ΔΨ m but this decline was significantly attenuated by ATRA. OGD-induced increase in [Ca 2+ ] i was also significantly attenuated by ATRA. Taken together with our previous results where calcium channel blockers reduced cell swelling, the effects of ATRA in attenuating swelling are possibly mediated through its effects in regulating [Ca 2+ ] i . Considering the paucity of agents in attenuating brain edema in ischemia, ATRA has the potential to reduce brain edema and associated neural damage in ischemic injury.

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A Novel, Nongenomic Mechanism Underlies Retinoic Acid-Induced Growth Cone Turning

Cited by 47 publications

References 38 publications

From carrot to clinic: an overview of the retinoic acid signaling pathway

From carrot to clinic: an overview of the retinoic acid signaling pathway

Retinoic acid affects calcium signaling in adult molluscan neurons

Acute effects of all-trans-retinoic acid in ischemic injury

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