Vitamin A Metabolism: Challenges and Perspectives

Ziouzenkova, Ouliana

doi:10.4172/2376-1318.1000e106

Cited by 3 publications

(4 citation statements)

References 46 publications

(64 reference statements)

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“…RA regulates a network of transcription factors and is a powerful therapeutic agent [ 33 ]. However, administration of RA is unspecific and causes numerous side effects known as “RA syndrome”.…”

Section: Discussionmentioning

confidence: 99%

“…RA induces differentiation of cells and regulates gene transcription, signaling events, and post-translational modification of proteins (reviewed in [ 26 , 33 ]). All isomers of RA are high affinity ligands for the retinoic acid receptor (RAR) (reviewed in [ 34 ]).…”

Section: Review Sectionmentioning

confidence: 99%

“…In contrast, Rald suppresses adipogenesis by inhibiting PPARγ and RXR activation [ 37 ]. PPARγ, RAR, and RXR regulate numerous differentiation processes and immune response [ 26 , 33 , 34 , 35 ]. Considering the role of ALDH1in controlling RA and Rald concentrations, it is possible that ALDH1 plays a role in the auto-/paracrine switch regulating adipogenesis and various other differentiation processes.…”

Section: Review Sectionmentioning

confidence: 99%

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Aldehyde Dehydrogenase 1A1: Friend or Foe to Female Metabolism?

2014

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In this review, we summarize recent advances in understanding vitamin A-dependent regulation of sex-specific differences in metabolic diseases, inflammation, and certain cancers. We focus on the characterization of the aldehyde dehydrogenase-1 family of enzymes (ALDH1A1, ALDH1A2, ALDH1A3) that catalyze conversion of retinaldehyde to retinoic acid. Additionally, we propose a “horizontal transfer of signaling” from estrogen to retinoids through the action of ALDH1A1. Although estrogen does not directly influence expression of Aldh1a1, it has the ability to suppress Aldh1a2 and Aldh1a3, thereby establishing a female-specific mechanism for retinoic acid generation in target tissues. ALDH1A1 regulates adipogenesis, abdominal fat formation, glucose tolerance, and suppression of thermogenesis in adipocytes; in B cells, ALDH1A1 plays a protective role by inducing oncogene suppressors Rara and Pparg. Considering the conflicting responses of Aldh1a1 in a multitude of physiological processes, only tissue-specific regulation of Aldh1a1 can result in therapeutic effects. We have shown through successful implantation of tissue-specific Aldh1a1−/− preadipocytes that thermogenesis can be induced in wild-type adipose tissues to resolve diet-induced visceral obesity in females. We will briefly discuss the emerging role of ALDH1A1 in multiple myeloma, the regulation of reproduction, and immune responses, and conclude by discussing the role of ALDH1A1 in future therapeutic applications.

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Section: Discussionmentioning

confidence: 99%

Section: Review Sectionmentioning

confidence: 99%

Section: Review Sectionmentioning

confidence: 99%

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Aldehyde Dehydrogenase 1A1: Friend or Foe to Female Metabolism?

2014

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“…RA binding to RAR induces its heterodimerization with retinoid X receptor, and binding to cognate response element (RARE) sequences in the promoters of target genes [18]. In addition, RA regulates a plethora of signaling and transcriptional pathways [19], including a Zfp423 -dependent induction of Pparg expression [20]. Paracrine RA production by ALDH1 enzymes in dendritic cells plays an important role in B cell homing to the mucosa, and promotes IgA isotype class switching [21,22].…”

Section: 1 Introductionmentioning

confidence: 99%

Aldehyde dehydrogenase-1a1 induces oncogene suppressor genes in B cell populations

Yasmeen

Meyers

Álvarez

et al. 2013

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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The deregulation of B cell differentiation has been shown to contribute to autoimmune disorders, hematological cancers, and aging. We provide evidence that the retinoic acid-producing enzyme aldehyde dehydrogenase 1a1 (Aldh1a1) is an oncogene suppressor in specific splenic IgG1+/CD19− and IgG1+/CD19+ B cells populations. Aldh1a1 regulated transcription factors during B cell differentiation in a sequential manner: 1) retinoic acid receptor alpha (Rara) in IgG1+/CD19− and 2) zinc finger protein Zfp423 and peroxisome proliferator-activated receptor gamma (Pparg) in IgG1+/CD19+ splenocytes. In Aldh1a1−/− mice, splenic IgG1+/CD19− and IgG1+/CD19+ B cells acquired expression of proto-oncogenic genes c-Fos, c-Jun, and Hoxa10 that resulted in splenomegaly. Human multiple myeloma B cell lines also lack Aldh1a1 expression; however, ectopic Aldh1a1 expression rescued Rara and Znf423 expression in these cells. Our data highlight a mechanism by which an enzyme involved in vitamin A metabolism can improve B cell resistance to oncogenesis.

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Encapsulation and controlled release of retinol from silicone particles for topical delivery

Shields

White

Osta

et al. 2018

Journal of Controlled Release

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Retinol, a derivative of vitamin A, is a ubiquitous compound used to treat acne, reduce wrinkles and protect against conditions like psoriasis and ichthyosis. While retinol is used as the primary active ingredient (AI) in many skin care formulations, its efficacy is often limited by an extreme sensitivity to degrade and toxicity at high concentrations. While microencapsulation is an appealing method to help overcome these issues, few microencapsulation strategies have made a major translational impact due to challenges with complexity, cost, limited protection of the AI and poor control of the release of the AI. We have developed a class of silicone particles that addresses these challenges for the encapsulation, protection and controlled release of retinol and other hydrophobic compounds. The particles are prepared by the sol-gel polymerization of silane monomers, which enables their rapid and facile synthesis at scale while maintaining a narrow size distribution (i.e., CV < 20%). We show that our particles can: (i) encapsulate retinol with high efficiency (>85%), (ii) protect retinol from degradation (yielding a half-life 9× greater than unencapsulated retinol) and (iii) slowly release retinol over several hours (at rates from 0.14 to 0.67 μg cm s). To demonstrate that the controlled release of retinol from the particles can reduce irritation, we performed a double blind study on human subjects and found that formulations containing our particles were 12-23% less irritating than identical formulations containing Microsponge® particles (an industry standard by Amcol, Inc.). To show that the silicone particles can elicit a favorable biological response, similar to the Microsponge® particles, we applied both formulations to reconstructed human epidermal tissues and found an upregulation of keratin 19 (K19) and a downregulation of K10, indicating that the reduced irritation observed in the human study was not caused by reduced activity. We also found a decrease in the production of interleukin-1α (IL-1α) compared to formulations containing the Microsponge particles, suggesting lower irritation levels and supporting the findings from the human study. Finally, we show that the silicone particles can encapsulate other AIs, including betamethasone, N, N-diethyl-meta-toluamide (DEET), homosalate and ingenol mebutate, establishing these particles as a true platform technology.

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Vitamin A Metabolism: Challenges and Perspectives

Cited by 3 publications

References 46 publications

Aldehyde Dehydrogenase 1A1: Friend or Foe to Female Metabolism?

Aldehyde Dehydrogenase 1A1: Friend or Foe to Female Metabolism?

Aldehyde dehydrogenase-1a1 induces oncogene suppressor genes in B cell populations

Encapsulation and controlled release of retinol from silicone particles for topical delivery

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