Aldehyde dehydrogenases: From eye crystallins to metabolic disease and cancer stem cells

Vasiliou, Vasilis; Thompson, David C.; Smith, Clay; Fujita, Mayumi; Chen, Ying

doi:10.1016/j.cbi.2012.10.026

Cited by 123 publications

(126 citation statements)

References 126 publications

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“…At least 19 genes contribute to the ALDH gene family (Vasiliou et al, 2013). Of these, RALDH1 ( ALDH1A1 ) was the first unequivocally identified to contribute physiologically to atRA biosynthesis (Posch et al, 1992).…”

Section: Diverse Metabolic Functions Of Cellular Retinol Binding-pmentioning

confidence: 99%

Cellular retinoid binding-proteins, CRBP, CRABP, FABP5: Effects on retinoid metabolism, function and related diseases

Napoli

2017

Pharmacology & Therapeutics

196

180

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Cellular binding-proteins (BP), including CRBP1, CRBP2, CRABP1, CRABP2, and FABP5, shepherd the poorly aqueous soluble retinoids during uptake, metabolism and function. Holo-BP promote efficient use of retinol, a scarce but essential nutrient throughout evolution, by sheltering it and its major metabolite all-trans-retinoic acid from adventitious interactions with the cellular milieu, and by imposing specificity of delivery to enzymes, nuclear receptors and other partners. Apo-BP reflect cellular retinoid status and modify activities of retinoid metabolon enzymes, or exert non-canonical actions. High ligand binding affinities and the nature of ligand sequestration necessitate external factors to prompt retinoid release from holo-BP. One or more of cross-linking, kinetics, and colocalization have identified these factors as RDH, RALDH, CYP26, LRAT, RAR and PPARβ/δ. Michaelis-Menten and other kinetic approaches verify that BP channel retinoids to select enzymes and receptors by protein-protein interactions. Function of the BP and enzymes that constitute the retinoid metabolon depends in part on retinoid exchanges unique to specific pairings. The complexity of these exchanges configure retinol metabolism to meet the diverse functions of all-trans-retinoic acid and its ability to foster contrary outcomes in different cell types, such as inducing apoptosis, differentiation or proliferation. Altered BP expression affects retinoid function, for example, by impairing pancreas development resulting in abnormal glucose and energy metabolism, promoting predisposition to breast cancer, and fostering more severe outcomes in prostate cancer, ovarian adenocarcinoma, and glioblastoma. Yet, the extent of BP interactions with retinoid metabolon enzymes and their impact on retinoid physiology remains incompletely understood.

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Section: Diverse Metabolic Functions Of Cellular Retinol Binding-pmentioning

confidence: 99%

Cellular retinoid binding-proteins, CRBP, CRABP, FABP5: Effects on retinoid metabolism, function and related diseases

Napoli

2017

Pharmacology & Therapeutics

196

180

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“…Despite aldehyde groups covering the BNP surface, the covalent linkage of these surface aldehydes to BNPs limits their distribution. Additionally, aldehydes are common in many foods and metabolites, which may confer high tolerance, and aldehyde groups can be readily detoxified by aldehyde dehydrogenase [33]. …”

Section: Discussionmentioning

confidence: 99%

Degradable bioadhesive nanoparticles for prolonged intravaginal delivery and retention of elvitegravir

et al. 2017

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New methods for long-lasting protection against sexually transmitted disease, such as the human immunodeficiency virus (HIV), are needed to help reduce the severity of STD epidemics, especially in developing countries. Intravaginal delivery of therapeutics has emerged as a promising means to provide women with local protection, but residence times of such agents are greatly reduced by the protective mucus layer, fluctuating hormone cycle, and complex anatomical structure of the reproductive tract. Polymeric nanoparticles (NPs) capable of encapsulating the desired cargo, penetrating through the mucosal surfaces, and delivering agents to the site of action have been explored. However, prolonged retention of polymer carriers and their enclosed materials may also be needed to ease adherence and confer longer-lasting protection against STDs. Here, we examined the fate of two poly(lactic acid)-hyperbranched polyglycerols (PLA-HPG) NP formulations – 1) nonadhesive PLA-HPG NPs (NNPs) and 2) surface-modified bioadhesive NPs (BNPs) – loaded with the antiretroviral elvitegravir (EVG) after intravaginal administration. BNP distribution was widespread throughout the reproductive tract, and retention was nearly 5 times higher than NNPs after 24h. Moreover, BNPs were found to be highly associated with submucosal leukocytes and epithelial cell populations for up to 48h after topical application, and EVG was retained significantly better in the vaginal lumen when delivered with BNPs as opposed to NNPs over a 24h period. Our results suggest that bioadhesive PLA-HPG NPs can greatly improve and prolong intravaginal delivery of agents, which may hold potential in providing sustained protection over longer durations.

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“…In addition to aldehyde metabolism, some ALDHs (e.g. ALDH2 and ALDH1A1) exhibit esterase and reductase catalytic activities [3,4]. Finally, ALDHs may also possess non-catalytic functions, such as structural or binding properties [5].…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic analysis and plasma metabolomics in Aldh16a1 -null mice reveals a potential role of ALDH16A1 in renal function

Charkoftaki

Chen

Han

et al. 2017

Chemico-Biological Interactions

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ALDH16A1 is a novel member of the ALDH superfamily that is enzymatically-inactive and highly expressed in the kidney. Recent studies identified an association between a rare missense single nucleotide variant (SNV) in the ALDH16A1 gene and elevated serum uric acid levels and gout. The present study explores the mechanisms by which ALDH16A1 influences uric acid homeostasis in the kidney. We generated and validated a mouse line with global disruption of the Aldh16a1 gene through gene targeting and performed RNA-seq analyses in the kidney of wild-type (WT) and Aldh16a1 knockout (KO) mice, along with plasma metabolomics. We found that ALDH16A1 is expressed in proximal and distal convoluted tubule cells in the cortex of the kidney and in zone 3 hepatocytes. RNA-seq and gene ontology enrichment analyses showed that cellular lipid and lipid metabolic processes are up-regulated. Three transporters localized in the apical membrane of the proximal convoluted tubule of the kidney known to influence urate/uric acid homeostasis were found to be up-regulated (Abcc4, Slc16a9) or down-regulated (Slc17a3). An initial metabolomics analysis in plasma revealed an altered lipid profile in KO mice that is in agreement with our RNA-seq analysis. This is the first study demonstrating a functional role of ALDH16A1 in the kidney.

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Aldehyde dehydrogenases: From eye crystallins to metabolic disease and cancer stem cells

Cited by 123 publications

References 126 publications

Cellular retinoid binding-proteins, CRBP, CRABP, FABP5: Effects on retinoid metabolism, function and related diseases

Cellular retinoid binding-proteins, CRBP, CRABP, FABP5: Effects on retinoid metabolism, function and related diseases

Degradable bioadhesive nanoparticles for prolonged intravaginal delivery and retention of elvitegravir

Transcriptomic analysis and plasma metabolomics in Aldh16a1 -null mice reveals a potential role of ALDH16A1 in renal function

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