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An Evolutionary Perspective of Dopachrome Tautomerase Enzymes in Metazoans.

ABSTRACT: Melanin plays a pivotal role in the cellular processes of several metazoans. The final step of the enzymically-regulated melanin biogenesis is the conversion of dopachrome into dihydroxyindoles, a reaction catalyzed by a class of enzymes called dopachrome tautomerases. We traced dopachrome tautomerase (DCT) and dopachrome converting enzyme (DCE) genes throughout metazoans and we could show that only one class is present in most of the phyla. While DCTs are typically found in deuterostomes, DCEs are present in several protostome phyla, including arthropods and mollusks. The respective DCEs belong to the yellow gene family, previously reported to be taxonomically restricted to insects, bacteria and fungi. Mining genomic and transcriptomic data of metazoans, we updated the distribution of DCE/yellow genes, demonstrating their presence and active expression in most of the lophotrochozoan phyla as well as in copepods (Crustacea). We have traced one intronless DCE/yellow gene through most of the analyzed lophotrochozoan genomes and we could show that it was subjected to genomic diversification in some species, while it is conserved in other species. DCE/yellow was expressed in most phyla, although it showed tissue specific expression patterns. In the parasitic copepod Mytilicola intestinalis DCE/yellow even belonged to the 100 most expressed genes. Both tissue specificity and high expression suggests that diverse functions of this gene family also evolved in other phyla apart from insects.

SUBMITTER: Rosani U

PROVIDER: S-EPMC6678240 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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An Evolutionary Perspective of Dopachrome Tautomerase Enzymes in Metazoans.

Rosani Umberto U Domeneghetti Stefania S Maso Lorenzo L Wegner K Mathias KM Venier Paola P

Genes 20190628 7

Melanin plays a pivotal role in the cellular processes of several metazoans. The final step of the enzymically-regulated melanin biogenesis is the conversion of dopachrome into dihydroxyindoles, a reaction catalyzed by a class of enzymes called dopachrome tautomerases. We traced dopachrometautomerase (DCT) and dopachrome converting enzyme (DCE) genes throughout metazoans and we could show that only one class is present in most of the phyla. While DCTs are typically found in ...[more]

PMID: 31261784

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Project description:Adipose tissue is a critical exchange center for complex energy transactions involving triacylglycerol storage and release. It also has an active endocrine role, releasing various adipose-derived cytokines (adipokines) that participate in complex pathways to maintain metabolic and vascular health. Here, we found D-dopachrome tautomerase (DDT) as an adipokine secreted from human adipocytes by a proteomic approach. DDT mRNA levels in human adipocytes were negatively correlated with obesity-related clinical parameters such as BMI, and visceral and subcutaneous fat areas. Experiments using SGBS cells, a human preadipocyte cell line, revealed that DDT mRNA levels were increased in an adipocyte differentiation-dependent manner and DDT was secreted from adipocytes. In DDT knockdown adipocytes differentiated from SGBS cells that were infected with the adenovirus expressing shRNA against the DDT gene, mRNA levels of genes involved in both lipolysis and lipogenesis were slightly but significantly increased. Furthermore, we investigated AMP-activated protein kinase (AMPK) signaling, which phosphorylates and inactivates enzymes involved in lipid metabolism, including hormone-sensitive lipase (HSL) and acetyl-CoA carboxylase (ACC), in DDT knockdown adipocytes. The AMPK phosphorylation of HSL Ser-565 and ACC Ser-79 was inhibited in DDT knockdown cells and recovered in the cells treated with recombinant DDT (rDDT), suggesting that down-regulated DDT in adipocytes brings about a state of active lipid metabolism. Furthermore, administration of rDDT in db/db mice improved glucose intolerance and decreased serum free fatty acids levels. In the adipose tissue from rDDT-treated db/db mice, not only increased levels of HSL phosphorylated by AMPK, but also decreased levels of HSL phosphorylated by protein kinase A (PKA), which phosphorylates HSL to promote its activity, were observed. These results suggested that DDT acts on adipocytes to regulate lipid metabolism through AMPK and/or PKA pathway(s) and improves glucose intolerance caused by obesity.

Project description:BackgroundThe human (Homo sapiens) chemokine-like protein macrophage migration inhibitory factor (HsMIF) is a pivotal mediator of inflammatory, infectious and immune diseases including septic shock, colitis, malaria, rheumatoid arthritis, and atherosclerosis, as well as tumorigenesis. HsMIF has been found to exhibit several sequential and three-dimensional sequence motifs that in addition to its receptor binding sites include catalytic sites for oxidoreductase and tautomerase activity, which provide this 12.5 kDa protein with a remarkable functional complexity. A human MIF paralog, D-dopachrome tautomerase (HsDDT), has been identified, but its physiological relevance is incompletely understood. MIF/DDT-like proteins have been described in animals, protists and bacteria. Although based on sequence data banks the presence of MIF/DDT-like proteins has also been recognized in the model plant species Arabidopsis thaliana, details on these plant proteins have not been reported.ResultsTo broaden the understanding of the biological role of these proteins across kingdoms we performed a comprehensive in silico analysis of plant MIF/DDT-like (MDL) genes/proteins. We found that the A. thaliana genome harbors three MDL genes, of which two are chiefly constitutively expressed in aerial plant organs, while the third gene shows stress-inducible transcript accumulation. The product of the latter gene likely localizes to peroxisomes. Structure prediction suggests that all three Arabidopsis proteins resemble the secondary and tertiary structure of human MIF. MIF-like proteins are found in all species across the plant kingdom, with an increasing family complexity towards evolutionarily advanced plant taxa. Plant MDL proteins are predicted to lack oxidoreductase activity, but possibly share tautomerase activity with human MIF/DDT.ConclusionsPeroxisome localization seems to be a specific feature of a subset of MIF/DDT orthologs found in dicotyledonous plant species, which together with its stress-inducible gene expression might point to convergent evolution in higher plants and vertebrates towards neofunctionalization of MIF/MDL proteins in stress response pathways including innate immunity.

Dataset Information

An Evolutionary Perspective of Dopachrome Tautomerase Enzymes in Metazoans.

Publications

An Evolutionary Perspective of Dopachrome Tautomerase Enzymes in Metazoans.

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