Identification and characterization of retinoid-active short-chain dehydrogenases/reductases in Drosophila melanogaster

Abstract

Background In chordates, retinoid metabolism is an important target of short-chain dehydrogenases/reductases (SDRs). It is not known whether SDRs play a role in retinoid metabolism of protostomes, such as Drosophila melanogaster. Methods Drosophila genome was searched for genes encoding proteins with ∼50% identity to human retinol dehydrogenase 12 (RDH12). The corresponding proteins were expressed in Sf9 cells and biochemically characterized. Their phylogenetic relationships were analyzed using PHYLIP software. Results A total of six Drosophila SDR genes were identified. Five of these genes are clustered on chromosome 2 and one is located on chromosome X. The deduced proteins are 300 to 406 amino acids long and are associated with microsomal membranes. They recognize all-trans-retinaldehyde and all-trans-3-hydroxyretinaldehyde as substrates and prefer NADPH as a cofactor. Phylogenetically, Drosophila SDRs belong to the same branch of the SDR superfamily as human RDH12, indicating a common ancestry early in bilaterian evolution, before protostome-deuterostome split. Conclusions Similarities in the substrate and cofactor specificities of Drosophila versus human SDRs suggest conservation of their function in retinoid metabolism throughout protostome and deuterostome phyla. General Significance The discovery of Drosophila retinaldehyde reductases sheds new light on the conversion of β-carotene and zeaxantine to visual pigment and provides a better understanding of the evolutionary roots of retinoid-active SDRs.

Chronic exposure to imidacloprid or thiamethoxam neonicotinoid causes oxidative damages and alters carotenoid-retinoid levels in caged honey bees (Apis mellifera)

“…So far, NinaB, an isomeroxygenase that combines carotene oxygenase and retinoid isomerase functions, was found in several insect species 40 and appears to use many carotenoids such as α/β-carotene, β-cryptoxanthin, lutein and zeaxanthin as substrates in order to produce various proportions of RALD isomers 40 , 41 . In D. melanogaster , short chain dehydrogenases (SDRs) were shown to be biochemically similar to the human Rdh12 42 . These SDRs were assumed to convert all- trans -RALD or all- trans -3-hydroxy-RALD to ROL isomers and might also be implicated in the reverse reaction in some cell types 42 .…”

“…In D. melanogaster , short chain dehydrogenases (SDRs) were shown to be biochemically similar to the human Rdh12 42 . These SDRs were assumed to convert all- trans -RALD or all- trans -3-hydroxy-RALD to ROL isomers and might also be implicated in the reverse reaction in some cell types 42 . Human Aldh1a orthologous genes found in some insects suggest potential enzyme candidates for the oxidation of RALD to RA 43 .…”

RDH12Mutations Cause a Severe Retinal Degeneration With Relatively Spared Rod Function

“…RDH12 localizes to the rod and cone photoreceptor inner segment and is able to reduce all-trans-and all-cis retinoids. 11,58,59 Murine Rdh12 knockouts, however, do not show an overt retinal degeneration or major slowing of the visual cycle. 58,60,61 Redundancy of retinal dehydrogenases, specifically RDH8, has been offered as an explanation for this discrepancy or a different role of RDH12 in humans compared to the murine model.…”

Enzymology of retinoic acid biosynthesis and degradation

“…At least six homologs of these genes sharing ‫ف‬ 50% identity to human RDH12 can be found in the genome of Drosophila melanogaster . The proteins encoded by the Drosophila genes are 300-406 amino acids long and are associated with microsomal membranes ( 84 ). They recognize all-trans -retinaldehyde and all-trans -3-hydroxyretinaldehyde as substrates and prefer NADPH as a cofactor.…”