Cyp26a1 supports postnatal retinoic acid homeostasis and glucoregulatory control

Yoo, Hong Sik; Cockrum, Michael A; Napoli, Joseph L.

doi:10.1016/j.jbc.2023.104669

Cited by 6 publications

(2 citation statements)

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“…In the case of ATRA-responsive NB4 cells and ATRA-non-responsive K562 cells, ANGPTL4 and CYP26A1 were the most up-regulated DEGs induced by the ATRA treatment. In mammals, ATRA regulates various developmental processes, including brain formation and myeloid hematopoiesis [20]. At the same time, the optimal level of ATRA should be maintained during development, as retinoids are teratogenic [21].…”

Section: Discussionmentioning

confidence: 99%

Systems Biology for Drug Target Discovery in Acute Myeloid Leukemia

Novikova,

Tolstova,

Kurbatov

et al. 2024

IJMS

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Combining new therapeutics with all-trans-retinoic acid (ATRA) could improve the efficiency of acute myeloid leukemia (AML) treatment. Modeling the process of ATRA-induced differentiation based on the transcriptomic profile of leukemic cells resulted in the identification of key targets that can be used to increase the therapeutic effect of ATRA. The genome-scale transcriptome analysis revealed the early molecular response to the ATRA treatment of HL-60 cells. In this study, we performed the transcriptomic profiling of HL-60, NB4, and K562 cells exposed to ATRA for 3-72 h. After treatment with ATRA for 3, 12, 24, and 72 h, we found 222, 391, 359, and 1032 differentially expressed genes (DEGs) in HL-60 cells, as well as 641, 1037, 1011, and 1499 DEGs in NB4 cells. We also found 538 and 119 DEGs in K562 cells treated with ATRA for 24 h and 72 h, respectively. Based on experimental transcriptomic data, we performed hierarchical modeling and determined cyclin-dependent kinase 6 (CDK6), tumor necrosis factor alpha (TNF-alpha), and transcriptional repressor CUX1 as the key regulators of the molecular response to the ATRA treatment in HL-60, NB4, and K562 cell lines, respectively. Mapping the data of TMT-based mass-spectrometric profiling on the modeling schemes, we determined CDK6 expression at the proteome level and its down-regulation at the transcriptome and proteome levels in cells treated with ATRA for 72 h. The combination of therapy with a CDK6 inhibitor (palbociclib) and ATRA (tretinoin) could be an alternative approach for the treatment of acute myeloid leukemia (AML).

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Section: Discussionmentioning

confidence: 99%

Systems Biology for Drug Target Discovery in Acute Myeloid Leukemia

Novikova,

Tolstova,

Kurbatov

et al. 2024

IJMS

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“…Lipid and Cholesterol Metabolism: Cyp26a1, Pnpla5, Prap1, and Fdps Cyp26a1, a retinoic acid-metabolizing enzyme, is downregulated by glucagon and cortisol secreted during fasting. Pnpla5 is involved in diacylglycerol production and promotes lipid droplet formation [37]. It is highly activated in the liver of obese (ob/ob) mice, and its expression is suppressed by fasting [38].…”

Section: Key Genes Whose Expression Was Decreased By Galpmentioning

confidence: 99%

Transcriptomic (DNA Microarray) and Metabolome (LC-TOF-MS) Analyses of the Liver in High-Fat Diet Mice after Intranasal Administration of GALP (Galanin-like Peptide)

Takenoya,

Shibato,

Yamashita

et al. 2023

IJMS

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The aim of this research was to test the efficacy and potential clinical application of intranasal administration of galanin-like peptide (GALP) as an anti-obesity treatment under the hypothesis that GALP prevents obesity in mice fed a high-fat diet (HFD). Focusing on the mechanism of regulation of lipid metabolism in peripheral tissues via the autonomic nervous system, we confirmed that, compared with a control (saline), intranasally administered GALP prevented further body weight gain in diet-induced obesity (DIO) mice with continued access to an HFD. Using an omics-based approach, we identified several genes and metabolites in the liver tissue of DIO mice that were altered by the administration of intranasal GALP. We used whole-genome DNA microarray and metabolomics analyses to determine the anti-obesity effects of intranasal GALP in DIO mice fed an HFD. Transcriptomic profiling revealed the upregulation of flavin-containing dimethylaniline monooxygenase 3 (Fmo3), metallothionein 1 and 2 (Mt1 and Mt2, respectively), and the Aldh1a3, Defa3, and Defa20 genes. Analysis using the DAVID tool showed that intranasal GALP enhanced gene expression related to fatty acid elongation and unsaturated fatty acid synthesis and downregulated gene expression related to lipid and cholesterol synthesis, fat absorption, bile uptake, and excretion. Metabolite analysis revealed increased levels of coenzyme Q10 and oleoylethanolamide in the liver tissue, increased levels of deoxycholic acid (DCA) and taurocholic acid (TCA) in the bile acids, increased levels of taurochenodeoxycholic acid (TCDCA), and decreased levels of ursodeoxycholic acid (UDCA). In conclusion, intranasal GALP administration alleviated weight gain in obese mice fed an HFD via mechanisms involving antioxidant, anti-inflammatory, and fatty acid metabolism effects and genetic alterations. The gene expression data are publicly available at NCBI GSE243376.

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The interplay between retinoic acid binding proteins and retinoic acid degrading enzymes in modulating retinoic acid concentrations

Isoherranen,

Wen

2024

Current Topics in Developmental Biology

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Cyp26a1 supports postnatal retinoic acid homeostasis and glucoregulatory control

Cited by 6 publications

References 50 publications

Systems Biology for Drug Target Discovery in Acute Myeloid Leukemia

Systems Biology for Drug Target Discovery in Acute Myeloid Leukemia

Transcriptomic (DNA Microarray) and Metabolome (LC-TOF-MS) Analyses of the Liver in High-Fat Diet Mice after Intranasal Administration of GALP (Galanin-like Peptide)

The interplay between retinoic acid binding proteins and retinoic acid degrading enzymes in modulating retinoic acid concentrations

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