Abstract
Aldose reductase (AKR1B) proteins are monomeric enzymes, belonging to the aldo-keto reductase (AKR) superfamily. They perform oxidoreduction of carbonyl groups from a wide variety of substrates, such as aliphatic and aromatic aldehydes or ketones. Due to the involvement of human aldose reductases in pathologies, such as diabetic complications and cancer, AKR1B subgroup enzymatic properties have been extensively characterized. However, the issue of AKR1B function in non-pathologic conditions remains poorly resolved. Adrenal activities generated large amount of harmful aldehydes from lipid peroxidation and steroidogenesis, including 4-hydroxynonenal (4-HNE) and isocaproaldehyde (4-methylpentanal), which can both be reduced by AKR1B proteins. More recently, some AKR1B isoforms have been shown to be endowed with prostaglandin F synthase (PGFS) activity, suggesting that, in addition to possible scavenger function, they could instigate paracrine signals. Interestingly, the adrenal gland is one of the major sites for human and murine AKR1B expression, suggesting that their detoxifying/signaling activity could be specifically required for the correct handling of adrenal function. Moreover, chronic effects of ACTH result in a coordinated regulation of genes encoding the steroidogenic enzymes and some AKR1B isoforms. This review presents the molecular mechanisms accounting for the adrenal-specific expression of some AKR1B genes. Using data from recent mouse genetic models, we will try to connect their enzymatic properties and regulation with adrenal functions.
Highlights
The pituitary adrenocorticotropic hormone is the main regulator of adrenal steroidogenesis acting through the cAMP-dependent protein kinase (PKA) signaling pathway
This review presents the molecular mechanisms accounting for the adrenal-specific expression of some AKR family 1 member B (AKR1B) genes
They are organized in two subgroups based on their ability to reduce glucose: aldose reductases (AR; AKR family 1 member B1 (AKR1B1)–6) and aldose reductase-like proteins (ARLP; Akr1b7–19), respectively [4, 10,11,12]
Summary
The pituitary adrenocorticotropic hormone is the main regulator of adrenal steroidogenesis acting through the cAMP-dependent protein kinase (PKA) signaling pathway. The AKR1B subfamily includes proteins sharing a high degree of similarity (i.e., more than 65% of identity; Table 1) They are organized in two subgroups based on their ability to reduce glucose: aldose reductases (AR; AKR1B1–6) and aldose reductase-like proteins (ARLP; Akr1b7–19), respectively [4, 10,11,12]. Their structure, enzymatic properties, and substrate specificities have been the subject of many studies [1, 5, 7, 13,14,15,16,17], emphasizing that in addition to their high percentage of identity, they display redundant substrate specificities and overlapping expression patterns. Analysis of murine genetic models and identification of the mechanisms regulating their expression are the necessary steps to complete our understanding in AKR1Bs biological function
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