Aldehyde dehydrogenase 1A3 is transcriptionally activated by all-trans-retinoic acid in human epidermal keratinocytes

All-trans retinoic acid (ATRA) influences cellular proliferation and differentiation but its mechanisms of action are not understood in keratinocytes. To investigate the potential mechanisms of action of ATRA in keratinocytes, microarray analysis of ATRA-treated normal human epidermal keratinocytes (NHEKs) was performed. Based on microarray data, we focused on insulin-like growth factor binding protein-6 (IGFBP-6), which is known to inhibit cellular senescence but has not been previously investigated in the context of ATRA-induced signaling in NHEKs. We verified that ATRA significantly increased IGFBP-6 gene and protein expression in NHEKs. Next, the effects of ATRA and IGFBP-6 on cell proliferation and senescence in H2O2-treated NHEKs were examined. IGFBP-6 was knocked-down using siRNA or overexpressed using pCMV-IGFBP-6. Cellular proliferation was observed using the bromodeoxyuridine (BrdU) incorporation assay. Cellular senescence was determined by monitoring SA-?-Gal staining and p21 expression. When IGFBP-6 was knocked down, cellular proliferation was inhibited, and the cellular senescence markers were increased. IGFBP-6 overexpression or ATRA treatment of H2O2-treated NHEKs rescued these effects. Taken together, our results suggest that ATRA prevents premature senescence-related skin damage at least in part by increasing IGFBP-6 expression, as shown herein in reactive oxygen species (ROS)-stimulated NHEKs.

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Response of Aldehyde Dehydrogenase (ALDH) after Cisplatin and All-Trans Retinoic Acid (ATRA) treatment of Spheroid-derived Cells (SDCs) from cervical cancer cell lines

10.1055/s-0038-1671355 ◽

2018 ◽

Cited By ~ 1

Author(s):

J Xu ◽

J Sehouli ◽

AM Kaufmann

Keyword(s):

Cervical Cancer ◽

Retinoic Acid ◽

Cell Lines ◽

Cancer Cell ◽

Aldehyde Dehydrogenase ◽

Cancer Cell Lines ◽

Cervical Cancer Cell ◽

Atra Treatment ◽

Trans Retinoic Acid ◽

All Trans Retinoic Acid

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All-trans Retinoic Acid-Induced Hyaluronan Production and Hyperplasia Are Partly Mediated by EGFR Signaling in Epidermal Keratinocytes

Journal of Investigative Dermatology ◽

10.1038/sj.jid.5701098 ◽

2008 ◽

Vol 128 (4) ◽

pp. 797-807 ◽

Cited By ~ 38

Author(s):

Sanna M. Pasonen-Seppänen ◽

Edward V. Maytin ◽

Kari J. Törrönen ◽

Juha M.T. Hyttinen ◽

Vincent C. Hascall ◽

...

Keyword(s):

Retinoic Acid ◽

Epidermal Keratinocytes ◽

Egfr Signaling ◽

Trans Retinoic Acid ◽

All Trans Retinoic Acid

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Developmental role of endogenous retinoids in the determination of morphallactic field in budding tunicates

Development ◽

10.1242/dev.117.3.835 ◽

1993 ◽

Vol 117 (3) ◽

pp. 835-845 ◽

Cited By ~ 1

Author(s):

K. Kawamura ◽

K. Hara ◽

S. Fujiwara

Keyword(s):

Retinoic Acid ◽

Aldehyde Dehydrogenase ◽

Ectopic Expression ◽

Trans Retinoic Acid ◽

All Trans Retinoic Acid ◽

Proximal Extremity ◽

Developmental Role

We have extracted retinoids from the budding tunicate Polyandrocarpa misakiensis and, using HPLC, identified some major peaks as cis-retinal, all-trans-retinal and all-trans-retinoic acid, of which cis-retinal was most abundant (~2 micromolar). In developing buds, the amount of cis-retinal was about one-fifth that of the adult animals. In those buds, aldehyde dehydrogenase, which could metabolize retinal in vitro, was expressed in epithelial cells and then in mesenchymal cells at the proximal extremity, that is, the future developmental field of the bud. Exogenous retinoic acid comparable to the endogenous level could induce an additional field at the distal end of the bud, resulting in a double monster. The induction always accompanied an ectopic expression of aldehyde dehydrogenase. The results of this work suggest that retinoic acid or related molecule(s) act as an endogenous trigger of morphallactic development of Polyandrocarpa buds.

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A novel isoenzyme of aldehyde dehydrogenase specifically involved in the biosynthesis of 9-cis and all-trans retinoic acid

Biochemical Journal ◽

10.1042/bj3050681 ◽

1995 ◽

Vol 305 (2) ◽

pp. 681-684 ◽

Cited By ~ 71

Author(s):

J Labrecque ◽

F Dumas ◽

A Lacroix ◽

P V Bhat

Keyword(s):

Retinoic Acid ◽

Aldehyde Dehydrogenase ◽

High Efficiency ◽

Rat Kidney ◽

Ph Optimum ◽

Retinoic Acids ◽

Trans Retinoic Acid ◽

All Trans Retinoic Acid ◽

X Receptors ◽

Specific Ligand

The pleiotropic effects of retinoids are mediated by two families of nuclear receptors: RAR (retinoic acid receptors) and RXR (retinoid X receptors). 9-cis-Retinoic acid is a specific ligand for RXR receptors, whereas either 9-cis- or all-trans-retinoic acid activates the RAR receptor family. The existence of RXRs suggests a new role for isomerization in the biology of retinoic acid. We report here the identification of an aldehyde dehydrogenase in the rat kidney that catalysed the oxidation of 9-cis- and all-trans-retinal to corresponding retinoic acids with high efficiency, 9-cis-retinal being 2-fold more active than all-trans-retinal. Based on several criteria, such as amino acid sequence, pH optimum, and inhibition by chloral hydrate, this enzyme was found to be a novel isoenzyme of aldehyde dehydrogenase. 9-cis-Retinol, the precursor for the biosynthesis of 9-cis-retinal was identified in the rat kidney. The occurrence of endogenous 9-cis-retinol and the existence of specific dehydrogenase which participates in the catalysis of 9-cis-retinal suggest that all-trans-retinoi(d) isomerization to 9-cis-retinoi(d) occurs at the retinol level, analogous to all-trans-retinol isomerization to 11-cis-retinol in the visual cycle.

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