TY - JOUR A1 - Vignon-Zellweger, Nicolas A1 - Rahnenführer, Jan A1 - Theuring, Franz A1 - Hocher, Berthold T1 - Analysis of cardiac and renal endothelin receptors by in situ hybridization in mice JF - Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion N2 - Background: Endothelin-1 (ET-1) is a multifunctional peptide, which is implicated in the renal and cardiac physicology as well as in many pathologies of these systems. ET-1's actions take place after the activation of two receptors: ETA and ETB. The expression of these receptors may be modulated during the pathologic process. The analysis of the distribution and level of expression of the receptors in animal models is therefore crucial. Methods: We developed a protocol for non-radioactive in situ hybridization for the mRNA of the two endothelin receptors on paraffin-embedded tissue using digoxigenin-labeled RNA probes. Results: In heart and kidney, the staining was reliable and specific. In a mouse model for endothelin/nitric oxide imbalance, cardiac ETB expression was reduced. The distribution of the receptors was in accordance with the actual knowledge. Differences in cell specific expression are discussed. Conclusions: We developed a protocol for the in situ hybridization of the endothelin receptors in mice. Given that the endothelin system is implicated in the development of many diseases, we believe that this protocol may be useful for a number of future preclinical studies. KW - Endothelin-1 KW - endothelin receptors KW - in situ hybridization KW - mouse Y1 - 2012 U6 - https://doi.org/10.7754/Clin.Lab.2012.120216 SN - 1433-6510 VL - 58 IS - 9-10 SP - 939 EP - 949 PB - Clin Lab Publ., Verl. Klinisches Labor CY - Heidelberg ER - TY - JOUR A1 - Terao, Mineko A1 - Garattini, Enrico A1 - Romão, Maria João A1 - Leimkühler, Silke T1 - Evolution, expression, and substrate specificities of aldehyde oxidase enzymes in eukaryotes JF - The journal of biological chemistry N2 - Aldehyde oxidases (AOXs) are a small group of enzymes belonging to the larger family of molybdo-flavoenzymes, along with the well-characterized xanthine oxidoreductase. The two major types of reactions that are catalyzed by AOXs are the hydroxylation of heterocycles and the oxidation of aldehydes to their corresponding carboxylic acids. Different animal species have different complements of AOX genes. The two extremes are represented in humans and rodents; whereas the human genome contains a single active gene (AOX1), those of rodents, such as mice, are endowed with four genes (Aox1-4), clustering on the same chromosome, each encoding a functionally distinct AOX enzyme. It still remains enigmatic why some species have numerous AOX enzymes, whereas others harbor only one functional enzyme. At present, little is known about the physiological relevance of AOX enzymes in humans and their additional forms in other mammals. These enzymes are expressed in the liver and play an important role in the metabolisms of drugs and other xenobiotics. In this review, we discuss the expression, tissue-specific roles, and substrate specificities of the different mammalian AOX enzymes and highlight insights into their physiological roles. KW - metalloenzyme KW - molybdenum KW - mouse KW - drug metabolism KW - flavoprotein KW - xenobiotic KW - oxidase KW - oxygen radicals KW - iron-sulfur protein KW - aldehyde oxidase (AOX) KW - enzyme evolution KW - metal-containing enzyme KW - molybdenum cofactor (Moco) KW - molybdo-flavoenzyme KW - 2Fe-2S cluster KW - flavin adenine dinucleotide (FAD) Y1 - 2020 U6 - https://doi.org/10.1074/jbc.REV119.007741 SN - 0021-9258 SN - 1083-351X VL - 295 IS - 16 SP - 5377 EP - 5389 PB - American Society for Biochemistry and Molecular Biology CY - Rockville ER - TY - JOUR A1 - Fedders, Ronja A1 - Muenzner, Matthias A1 - Weber, Pamela A1 - Sommerfeld, Manuela A1 - Knauer, Miriam A1 - Kedziora, Sarah A1 - Kast, Naomi A1 - Heidenreich, Steffi A1 - Raila, Jens A1 - Weger, Stefan A1 - Henze, Andrea A1 - Schupp, Michael T1 - Liver-secreted RBP4 does not impair glucose homeostasis in mice JF - The journal of biological chemistry N2 - Retinol-binding protein 4 (RBP4) is the major transport protein for retinol in blood. Recent evidence from genetic mouse models shows that circulating RBP4 derives exclusively from hepatocytes. Because RBP4 is elevated in obesity and associates with the development of glucose intolerance and insulin resistance, we tested whether a liver-specific overexpression of RBP4 in mice impairs glucose homeostasis. We used adeno-associated viruses (AAV) that contain a highly liver-specific promoter to drive expression of murine RBP4 in livers of adult mice. The resulting increase in serum RBP4 levels in these mice was comparable with elevated levels that were reported in obesity. Surprisingly, we found that increasing circulating RBP4 had no effect on glucose homeostasis. Also during a high-fat diet challenge, elevated levels of RBP4 in the circulation failed to aggravate the worsening of systemic parameters of glucose and energy homeostasis. These findings show that liver-secreted RBP4 does not impair glucose homeostasis. We conclude that a modest increase of its circulating levels in mice, as observed in the obese, insulin-resistant state, is unlikely to be a causative factor for impaired glucose homeostasis. KW - liver KW - retinoid-binding protein KW - glucose metabolism KW - insulin resistance KW - mouse KW - TTR Y1 - 2018 U6 - https://doi.org/10.1074/jbc.RA118.004294 SN - 1083-351X VL - 293 IS - 39 SP - 15269 EP - 15276 PB - American Society for Biochemistry and Molecular Biology CY - Bethesda ER -