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Effects of Retinoids at the Cellular Level (Differentiation, Apoptosis, Autophagy, Cell Cycle Regulation, and Senescence)
Published in Ayse Serap Karadag, Berna Aksoy, Lawrence Charles Parish, Retinoids in Dermatology, 2019
The entry of RA into the nucleus, where binding to receptors occurs, depends upon the retinoid binding proteins. These cytosolic proteins include cellular retinol-binding proteins (RBP): RBP1, RBP2, cellular retinoic acid-binding protein 1 and 2 (CRABP1, CRABP2), and fatty acid-binding protein 5 (FABP5), which are responsible for cellular transport of poorly soluble retinoids during uptake, metabolism, and function (5).
Hair and Nail Manifestations of HIV Infection
Published in Clay J. Cockerell, Antoanella Calame, Cutaneous Manifestations of HIV Disease, 2012
Gabriela M. Blanco, Frankie G. Rholdon, Clay J. Cockerell
About 30% of patients taking indinavir develop one of many retinoid-like effects such as alopecia, xerosis, ingrown nails, and paronychia.109 Bouscarat et al. suggested that protease inhibitors have a retinoid-like effect due to homologies between the amino acid sequences of retinoic acid-binding protein 1(CRABP1) and the catalytic site of HIV-1 protease, the target site of protease inhibitors.110 It is hypothesized that indinavir may interfere with retinoid metabolism by either enhancing the retinoid signaling pathway, increasing the synthesis of retinoic acid, or decreasing the P450-mediated oxidative metabolism of retinoic acid.
All-Trans Retinoic Acid Prevents the Progression of Gastric Precancerous Lesions by Regulating Disordered Retinoic Acid Metabolism
Published in Nutrition and Cancer, 2022
Hanhan Wu, Didi Zhao, Chen Wang, Daoming Zhang, Min Tang, Shiqing Qian, Lina Xu, Tao Xia, Juanyan Zhou, Guangjun Wang, Yue He, Lei Gao, Wenjun Chen, Li Li, Wanshui Yang, Qihong Zhao, Chuanlai Hu, Anla Hu
As the most biologically active metabolite of vitamin A, retinoic acid (RA) cannot be obtained directly from food but only vitamin A (retinol, retinyl ester, or carotenoids) from food that is metabolized in the body (11). Retinol is delivered to target cells bound to plasma retinol-binding protein (RBP). HoloRBP binds to RBP receptor, stimulated by retinoic acid gene 6 (STRA6) (12, 13). Cellular retinol-binding protein 1 (CRBP1) accepts retinol from STRA6 in the cytoplasm and delivers retinol to membranes, where retinol is either esterified by lecithin retinol acyltransferase (LRAT) to inactive retinyl ester or oxidized by retinol dehydrogenases (RDH) to retinal (14, 15). Retinal is oxidized further to RA by aldehyde dehydrogenases (ALDH) in the cytoplasm or is reduced back to retinol by retinal dehydrogenases in the membranes (14, 16). RA binds to cellular retinol acid-binding protein (CRABP1/2). Most RA is transferred by holoCRABP2 to the nucleus for binding to heterodimers of RA receptors (RARs) and retinoid X receptors (RXRs) in the target nucleus and thereafter triggers the downstream signaling pathways. The remainder is delivered to enzymes by holoCRABP1 for degradation. The clearance of RA is mediated predominantly by cytochrome P450 family 26 enzymes (CYP26). The family consists of three highly conserved enzymes, CYP26A1, CYP26B1, and CYP26C1 (17, 18). In addition, β-carotene is taken up by the cells and cleaved into retinal by β-carotene 15-15′-oxygenase (BCO1). Retinals derived from β-carotene may be oxidized to RA or converted to retinol (19).
All-trans retinoic acid in anticancer therapy: how nanotechnology can enhance its efficacy and resolve its drawbacks
Published in Expert Opinion on Drug Delivery, 2021
Gabriel Silva Marques Borges, Flávia Alves Lima, Guilherme Carneiro, Gisele Assis Castro Goulart, Lucas Antônio Miranda Ferreira
Altered catabolism by the CYP enzymes and ATRA sequestration by the cellular retinoic acid binding proteins (CRABP) are among the reasons listed for these bioavailability issues during the treatment [86]. CRABP1 and CRABP2 are proteins that can bind ATRA with high affinity and allow transportation of the hydrophobic ATRA in the aqueous cellular milieu. CRABP2 transport ATRA from the cytoplasm to the nucleus, allowing its binding to RAR. CRABP1 is related to ATRA catabolism, directing it to CYP enzymes. Several cancer cells less sensitive to ATRA, had enhanced expression of CRABP1 [87–90]. ATRA is metabolized by the CYP enzymes into a variety of polar metabolites and the main metabolism pathway is the 4-hydroxilation. Among the CYP enzymes, CYP26 seems to be to most specific for ATRA, and the subtypes CYP26A1 and CYP26B2 are the most studied ones. Many cancer types, including breast, colorectal, ovarian, and head and neck cancers show increased expression of CYP26 enzymes [87,91].