Beschreibung: Carbonyl reducing enzymes play important roles in the Phase I metabolism of many carbonyl group bearing xenobiotics (Fig. 1) [1,2]. On the other hand, these enzymes metabolize endogenous signal molecules such as steroid hormones, prostaglandines, biogenic amines, as well as sugars and lipid peroxidation derived carbonyls, and are therefore involved in the (patho)physiology of frequent diseases including diabetes, hypertension, the metabolic syndrome, osteoporosis, cancer and neurodegenerative disorders (Fig. 2)[3]. The importance of carbonyl reduction could be demonstrated in the model organism Drosophila melanogaster, where the carbonyl reductase „sniffer“ protects against age-dependent neurodegeneration [4,5]. The enzyme „sniffer“, a homodimeric carbonyl reductase that belongs to the shortchain dehydrogenase/reductase (SDR) superfamily, shares identity to the human enzyme carbonyl reductase type I (CBR1) [6,7]. „Sniffer“ is also common in other species like Daphnia, which are classical organisms for aquatic toxicity testing. Recently, the carbonyl reductase “sniffer” has been identified in the Blue mussel Mytilus spp. (Fig. 3). Millions of tonnes of munitions that have been dumped after World War II pose a new threat to the seas worldwide, since the metal vessels corrode and the toxic explosives trinitrotoluene (TNT) and metabolites leak into the environment [8,9]. Therefore, specific biomarkers are urgently sought to detect TNT contaminations and to perform a risk assessment both for the ecosphere and the human sea food consumer. In the present study, we provide evidence that TNT induces gene expression of the carbonyl reductase „sniffer“ in blue mussels.

Beschreibung: Millions of tons of all kind of munitions, including mines, bombs and torpedoes have been dumped after World War II in the marine environment and do now pose a new threat to the seas worldwide. Beside the acute risk of unwanted detonation, there is a chronic risk of contamination, because the metal vessels corrode and the toxic and carcinogenic explosives (trinitrotoluene (TNT) and metabolites) leak into the environment. While the mechanism of toxicity and carcinogenicity of TNT and its derivatives occurs through its capability of inducing oxidative stress in the target biota, we had the idea if TNT can induce the gene expression of carbonyl reductase in blue mussels. Carbonyl reductases are members of the short-chain dehydrogenase/reductase (SDR) superfamily. They metabolize xenobiotics bearing carbonyl functions, but also endogenous signal molecules such as steroid hormones, prostaglandins, biogenic amines, as well as sugar and lipid peroxidation derived reactive carbonyls, the latter providing a defence mechanism against oxidative stress and reactive oxygen species (ROS). Here, we identified and cloned the gene coding for carbonyl reductase from the blue mussel Mytilus spp. by a bioinformatics approach. In both laboratory and field studies, we could show that TNT induces a strong and concentration-dependent induction of gene expression of carbonyl reductase in the blue mussel. Carbonyl reductase may thus serve as a biomarker for TNT exposure on a molecular level which is useful to detect TNT contaminations in the environment and to perform a risk assessment both for the ecosphere and the human seafood consumer.