NRF2 Mediates Neuroblastoma Proliferation and Resistance to Retinoic Acid Cytotoxicity in a Model of In Vitro Neuronal Differentiation

2015 ◽  
Vol 53 (9) ◽  
pp. 6124-6135 ◽  
Author(s):  
Vitor de Miranda Ramos ◽  
Alfeu Zanotto-Filho ◽  
Matheus Augusto de Bittencourt Pasquali ◽  
Karina Klafke ◽  
Juciano Gasparotto ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Neuronal Differentiation

A posteriorising factor, retinoic acid, reveals that anteroposterior patterning controls the timing of neuronal differentiation in Xenopus neuroectoderm

Development ◽  
1996 ◽  
Vol 122 (11) ◽  
pp. 3409-3418 ◽  
Author(s):  
N. Papalopulu ◽  
C. Kintner
Keyword(s):  
Retinoic Acid ◽  
Neuronal Differentiation ◽  
Neural Tissue ◽  
Neural Plate ◽  
Neural Tube Closure ◽  
Proneural Gene ◽  
Anteroposterior Patterning ◽  
Neural Genes ◽  
Tube Closure

During early development of the Xenopus central nervous system (CNS), neuronal differentiation can be detected posteriorly at neural plate stages but is delayed anteriorly until after neural tube closure. A similar delay in neuronal differentiation also occurs in the anterior neural tissue that forms in vitro when isolated ectoderm is treated with the neural inducer noggin. Here we examine the factors that control the timing of neuronal differentiation both in embryos and in neural tissue induced by noggin (noggin caps). We show that the delay in neuronal differentiation that occurs in noggin caps cannot be overcome by inhibiting the activity of the neurogenic gene, X-Delta-1, which normally inhibits neuronal differentiation, suggesting that it represents a novel level of regulation. Conversely, we show that the timing of neuronal differentiation can be changed from late to early after treating noggin caps or embryos with retinoic acid (RA), a putative posteriorising agent. Concommittal with changes in the timing of neuronal differentiation, RA suppresses the expression of anterior neural genes and promotes the expression of posterior neural genes. The level of early neuronal differentiation induced by RA alone is greatly increased by the additional expression of the proneural gene, XASH3. These results indicate that early neuronal differentiation in neuralised ectoderm requires posteriorising signals, as well as signals that promote the activity of proneural genes such as XASH3. In addition, these result suggest that neuronal differentiation is controlled by anteroposterior (A-P) patterning, which exerts a temporal control on the onset of neuronal differentiation.

Neuronal differentiation of cloned human teratoma cells in response to retinoic acid in vitro

1986 ◽  
Vol 11 (1) ◽  
pp. 67-86 ◽  
Author(s):  
Michael Webb ◽  
Christopher Graham ◽  
Frank Walsh
Keyword(s):  
Retinoic Acid ◽  
Neuronal Differentiation

Inhibition by Carotenoids and Retinoic Acid of Osteoclast-Like Cell Formation Induced by Bone-Resorbing Agents In Vitro.

1999 ◽  
Vol 27 (3) ◽  
pp. 113-122 ◽  
Author(s):  
Yoshiko ISHIMI ◽  
Mineko OHMURA ◽  
Xinxiang WANG ◽  
Michio YAMAGUCHI ◽  
Sachie IKEGAMI
Keyword(s):  
Retinoic Acid ◽  
Cell Formation

Enhanced Oral Absorption of All-trans Retinoic Acid upon Encapsulation in Solid Lipid Nanoparticles

2020 ◽  
Vol 8 (6) ◽  
pp. 495-510
Author(s):  
Manoj Kumar ◽  
Garima Sharma ◽  
Dinesh Singla ◽  
Sukhjeet Singh ◽  
Vandita Kakkar ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Side Effects ◽  
Solid Lipid Nanoparticles ◽  
In Vitro Release ◽  
Lipid Nanoparticles ◽  
Solid Lipid ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Vitro Release

Background:: All-trans retinoic acid (ATRA) is widely employed in the treatment of various proliferative and inflammatory diseases. However, its therapeutic efficacy is imperiled due to its poor solubility and stability. Latter was surmounted by its incorporation into a solid matrix of lipidic nanoparticles (SLNs). Methods:: ATRA loaded SLNs (ATRA-SLNs) were prepared using a novel microemulsification technique (USPTO 9907758) and an optimal composition and were characterized in terms of morphology, differential scanning calorimetry (DSC), and powder X-ray diffraction studies (PXRD). In vitro release, oral plasma pharmacokinetics (in rats) and stability studies were also done. Results:: Rod-shaped ATRA-SLNs could successfully incorporate 3.7 mg/mL of ATRA, increasing its solubility (from 4.7 μg/mL) by 787 times, having an average particle size of 131.30 ± 5.0 nm and polydispersibility of 0.283. PXRD, DSC, and FTIR studies confirmed the formation of SLNs. Assay/total drug content and entrapment efficiency of ATRA-SLNs was 92.50 ± 2.10% and 84.60 ± 3.20% (n=6), respectively, which was maintained even on storage for one year under refrigerated conditions as an aqueous dispersion. In vitro release in 0.01 M phosphate buffer (pH 7.4) with 3% tween 80 was extended 12 times from 2h for free ATRA to 24 h for ATRA-SLNs depicting Korsmeyer Peppas release. Oral administration in rats showed 35.03 times enhanced bioavailability for ATRA-SLNs. Conclusion:: Present work reports preparation and evaluation of bioenhanced ATRA-SLNs containing a high concentration of ATRA (>15 times than that reported by others). Latter is attributed to the novel preparation process and intelligent selection of components. Lay Summary: All-trans retinoic acid (ATRA) shows an array of pharmacological activities but its efficacy is limited due to poor solubility, stability and side effects. In present study its solubility and efficacy is improved by 787 and 35.5 times, respectively upon incorporation into solid lipid nanoparticles (ATRA-SLNs). Latter extended its release by 12 times and provided stability for at least a year under refrigeration. A controlled and sustained release will reduce dose related side effects. ATRA-SLNs reported presently can thus be used in treatment /prophylaxis of disorders like cancers, tuberculosis, age related macular degeneration and acne and as an immune-booster.

scholarly journals All-Trans Retinoic Acid Increases DRP1 Levels and Promotes Mitochondrial Fission

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1202
Author(s):  
Bojjibabu Chidipi ◽  
Syed Islamuddin Shah ◽  
Michelle Reiser ◽  
Manasa Kanithi ◽  
Amanda Garces ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Mitochondrial Fission ◽  
Normal Function ◽  
Mitochondrial Network ◽  
Protein Levels ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Area And Perimeter

In the heart, mitochondrial homeostasis is critical for sustaining normal function and optimal responses to metabolic and environmental stressors. Mitochondrial fusion and fission are thought to be necessary for maintaining a robust population of mitochondria, and disruptions in mitochondrial fission and/or fusion can lead to cellular dysfunction. The dynamin-related protein (DRP1) is an important mediator of mitochondrial fission. In this study, we investigated the direct effects of the micronutrient retinoid all-trans retinoic acid (ATRA) on the mitochondrial structure in vivo and in vitro using Western blot, confocal, and transmission electron microscopy, as well as mitochondrial network quantification using stochastic modeling. Our results showed that ATRA increases DRP1 protein levels, increases the localization of DRP1 to mitochondria in isolated mitochondrial preparations. Our results also suggested that ATRA remodels the mitochondrial ultrastructure where the mitochondrial area and perimeter were decreased and the circularity was increased. Microscopically, mitochondrial network remodeling is driven by an increased rate of fission over fusion events in ATRA, as suggested by our numerical modeling. In conclusion, ATRA results in a pharmacologically mediated increase in the DRP1 protein. It also results in the modulation of cardiac mitochondria by promoting fission events, altering the mitochondrial network, and modifying the ultrastructure of mitochondria in the heart.

scholarly journals In vitro metabolism of retinoic acid in hamster intestine and liver.

1979 ◽  
Vol 254 (14) ◽  
pp. 6296-6302 ◽  
Author(s):  
A B Roberts ◽  
M D Nichols ◽  
D L Newton ◽  
M B Sporn
Keyword(s):  
Retinoic Acid ◽  
In Vitro Metabolism
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