Tissue localization of retinoic acid receptor (RAR) active drugs

Kouchmeshky, Azita; Goodman, Timothy; Whiting, Andrew; McCaffery, Peter

doi:10.1016/bs.mie.2020.03.012

Cited by 3 publications

(1 citation statement)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Retinol-binding protein transported vitamin A in the hydrophilic environment of the cytoplasm and regenerated visual pigments [ 56 , 57 ]. RAR was involved in the retinoic acid signaling pathway, which was crucial for the control of embryonic development [ 58 ]. The different living environments ( Cx.…”

Section: Discussionmentioning

confidence: 99%

Identification of differentially expressed genes based on antennae RNA-seq analyses in Culex quinquefasciatus and Culex pipiens molestus

Gao¹,

Gu²,

Xing³

et al. 2022

Parasites Vectors

View full text Add to dashboard Cite

Background Both Culex quinquefasciatus and Cx. pipiens molestus are sibling species within Cx. pipiens complex. Even though they are hard to distinguish morphologically, they have different physiological behaviors. However, the molecular mechanisms underlying these differences remain poorly understood. Methods Transcriptome sequencing was conducted on antennae of two sibling species. The identification of the differentially expressed genes (DEGs) was performed by the software DESeq2. Database for Annotation, Visualization and Integrated Discovery was used to perform GO pathway enrichment analysis. The protein–protein interaction (PPI) network was constructed with Cytoscape software. The hub genes were screened by the CytoHubba plugin and Degree algorithms. The identified genes were verified by quantitative real-time PCR. Results Most annotated transcripts (14,687/16,005) were expressed in both sibling species. Among 15 identified odorant-related DEGs, OBP10 was expressed 17.17 fold higher in Cx. pipiens molestus than Cx. quinquefasciatus. Eighteen resistance-related DEGs were identified, including 15 from CYP gene family and three from acetylcholinesterase, in which CYP4d1 was 86.59 fold more highly expressed in C. quinquefasciatus. Three reproductive DEGs were indentified with the expression from 5.01 to 6.55 fold. Among eight vision-related DEGs, retinoic acid receptor RXR-gamma in Cx. pipiens molestus group was more expressed with 214.08 fold. Among the 30 hub genes, there are 10 olfactory-related DEGs, 16 resistance-related DEGs, and four vision-related DEGs, with the highest score hub genes being OBP lush (6041148), CYP4C21 (6044704), and Rdh12 (6043932). The RT-qPCR results were consistent with the transcriptomic data with the correlation coefficient R = 0.78. Conclusion The study provided clues that antennae might play special roles in reproduction, drug resistance, and vision, not only the traditional olfactory function. OBP lush, CYP4C21, and Rdh12 may be key hints to the potential molecular mechanisms behind the two sibling species' biological differences. Graphical Abstract

show abstract

Section: Discussionmentioning

confidence: 99%

Identification of differentially expressed genes based on antennae RNA-seq analyses in Culex quinquefasciatus and Culex pipiens molestus

Gao¹,

Gu²,

Xing³

et al. 2022

Parasites Vectors

View full text Add to dashboard Cite

show abstract

The combined administration of LNC-encapsulated retinoic acid and calcitriol stimulates oligodendrocyte progenitor cell differentiation in vitro and in vivo after intranasal administration

Labrak,

Alhouayek,

Mwema

et al. 2024

International Journal of Pharmaceutics

View full text Add to dashboard Cite

Neuroprotective effects of ellorarxine in neuronal models of degeneration

Kouchmeshky,

Whiting,

McCaffery

2024

Front. Neurosci.

View full text Add to dashboard Cite

IntroductionRetinoic acid (RA) was first recognised to be important for the central nervous system (CNS) in its developmental regulatory role and, given this action, it has been proposed in the adult CNS to regulate plasticity and promote regeneration. These types of roles have included support of neurogenesis, induction of neurite outgrowth, and protection from neuronal death. These functions are predominantly mediated by the retinoic acid receptor (RAR) transcription factor, and hence agonists for the RARs have been tested in a variety of models of neurodegeneration. This present study employs several in vitro models less explored for the action of RAR agonists to reverse neurodegeneration.MethodsA series of assays are used in which neuronal cells are placed under the types of stress that have been linked to neurodegeneration, in particular amyotrophic lateral sclerosis (ALS), and the neuroprotective influence of a new potent agonist for RAR, ellorarxine, is tested out. In these assays, neuronal cells were subjected to excitotoxic stress induced by glutamate, proteostasis disruption caused by epoxomicin, and oxidative stress leading to stress granule formation triggered by sodium arsenite.ResultsEllorarxine effectively reversed neuronal death in excitotoxic and proteostasis disruption assays and mitigated stress granule formation induced by sodium arsenite. This study also highlights for the first time the novel observation of RAR modulation of stress granules, although it is unknown whether this change in stress granules will be neuroprotective or potentially regenerative. Furthermore, the distribution of RAR agonists following intraperitoneal injection was assessed in mice, revealing preferential accumulation in the central nervous system, particularly in the spinal cord, compared to the liver. Gene expression studies in the spinal cord demonstrated that ellorarxine induces transcriptional changes at a low dose (0.01 mg/kg).DiscussionThese findings underscore the therapeutic potential of RAR agonists, such as ellorarxine, for ALS and potentially other neurodegenerative diseases.

show abstract

Tissue localization of retinoic acid receptor (RAR) active drugs

Cited by 3 publications

References 36 publications

Identification of differentially expressed genes based on antennae RNA-seq analyses in Culex quinquefasciatus and Culex pipiens molestus

Identification of differentially expressed genes based on antennae RNA-seq analyses in Culex quinquefasciatus and Culex pipiens molestus

The combined administration of LNC-encapsulated retinoic acid and calcitriol stimulates oligodendrocyte progenitor cell differentiation in vitro and in vivo after intranasal administration

Neuroprotective effects of ellorarxine in neuronal models of degeneration

Contact Info

Product

Resources

About