Candidate genes for performance in horses, including monocarboxylate transporters

ABSTRACT: Some horse breeds are highly selected for athletic activities. The athletic potential of each animal can be measured by its performance in sports. High athletic performance depends on the animal capacity to produce energy through aerobic and anaerobic metabolic pathways, among other factors. Transmembrane proteins called monocarboxylate transporters, mainly the isoform 1 (MCT1) and its ancillary protein CD147, can help the organism to adapt to physiological stress caused by physical exercise, transporting lactate and H+ ions. Horse breeds are selected for different purposes so we might expect differences in the amount of those proteins and in the genotypic frequencies for genes that play a significant role in the performance of the animals. The study of MCT1 and CD147 gene polymorphisms, which can affect the formation of the proteins and transport of lactate and H+, can provide enough information to be used for selection of athletic horses increasingly resistant to intense exercise. Two other candidate genes, the PDK4 and DMRT3, have been associated with athletic potential and indicated as possible markers for performance in horses. The oxidation of fatty acids is highly effective in generating ATP and is controlled by the expression of PDK4 (pyruvate dehydrogenase kinase, isozyme 4) in skeletal muscle during and after exercise. The doublesex and mab-3 related transcription factor 3 (DMRT3) gene encodes an important transcription factor in the setting of spinal cord circuits controlling movement in vertebrates and may be associated with gait performance in horses. This review describes how the monocarboxylate transporters work during physical exercise in athletic horses and the influence of polymorphisms in candidate genes for athletic performance in horses

Effects of nitric oxide on the adhesion of human melanocytes to extracellular matrix components

The aim of the present study was to explore whether nitric oxide (NO) interferes with the attachment of human melanocytes to the extracellular matrix (ECM) components. Consequently, the effects have been investigated of the NO‐releasing compounds 3‐morpholino‐sydnonimine (SIN‐1) and S‐nitroso‐glutathione (GSNO) on the in vitro adhesion of human melanocytic cells to fibronectin. The NO donors induced a concentration‐dependent reduction in the adhesion of both 51CrO42−‐labelled melanocytes and melanoma cells to fibronectin. Pigmented M14 melanoma cells were more susceptible to the effect of SIN‐1 (half‐maximal inhibiting effect at about 0·5 mm) than normal human melanocytes and also than the non‐pigmented melanoma cells Mel57 (half‐maximal inhibiting effects between 0·9 and 2 mm). This effect of SIN‐1 also appeared to be related to the melanin content of normal melanocytes, whereas GSNO was significantly less active. Both flow cytometric analysis and immunocytochemical staining showed expression of neuronal NO synthase in all cell lines. The results of this study suggest that aberrant in vivo production of NO during infection and inflammation may contribute to loss of melanocytes in, for example, vitiligo, by reducing de novo attachment of melanocytes to the ECM. These findings could also be important for understanding the process of metastasis

Tenascin is overexpressed in vitiligo lesional skin and inhibits melanocyte adhesion

The aetiology of vitiligo remains obscure. In this study, the role of integrins in the observed inability of melanocytes to repopulate lesional skin was investigated. Antibodies directed to alpha 2, alpha 3, alpha 5, alpha v, alpha 6, beta 1 and beta 3 integrin subunits were used. Immunohistology revealed no marked differences in the overall levels of expression of integrins between control, non-lesional perilesional or lesional skin. Moreover, no differences were noted in the level of expression of integrins or the adhesive capacity between cultured control cells derived from three separate donors and vitiligo-derived melanocytes from two donors. Rather, it was clearly observed that towards the lesion, vitiligo skin contains increasing amounts of tenascin in the basal membrane and papillary dermis in five patients employing T2H5 antihuman tenascin antibody. The anti-adhesive effect observed in vitro for this extracellular matrix molecule using normal melanocytes may contribute to loss of pigment cells in vitiligo or to ineffective repopulation of the lesion

In vitro tissue-digesting properties of krill enzymes compared with fibrinolysin/DNAse, papain and placebo

Wound debridement, the removal of necrotic tissue, can be achieved with proteolytic enzymes. Recently, a new multi-enzyme preparation, krill enzyme, isolated from Antarctic shrimp-like organisms (Euphausia superba), was reported to possess powerful proteolytic activity towards protein substrates. In this paper, we study the in vitro digestive properties of krill enzymes towards whole tissue, compared with placebo, papain, and fibrinolysin/DNAse. Freshly obtained skin specimens were exposed for 3 days to krill enzymes (3; 0.6 and 0.06 U/ml), papain (120; 60; 6 and 0.6 U/ml), fibrinolysin/DNAse (2.5/1500 E and 1/600 E), and phosphate-buffered saline control solution. Tissue digestion was estimated by measuring wet wt, dry wt, and histological examination. After 72 hr of exposure to 3 U/ml krill enzymes, the dry wt of the specimens was reduced to 2.7% +/- 1.9 (SEM, n = 5), compared with 31.0% +/- 2.7 for placebo, 25.7% +/- 2.5 for 120 U/ml papain, and 24.5% +/- 3.3 for 2.5/1500 E/ml fibrinolysin/DNAse. The differences between krill enzymes and fibrinolysin/DNAse, papain, and control solution were statistically significant (p <0.007). These data suggest that krill enzymes are more active than other commonly available proteolytic agents used for wound debridemen