In silico investigation of uncoupling protein function in avian genomes

INTRODUCTION: The uncoupling proteins (UCPs) are involved in lipid metabolism and belong to a family of mitochondrial anionic transporters. In poultry, only one UCP homologue has been identified and experimentally shown to be associated with growth, feed conversion ratio, and abdominal fat according to its predominant expression in bird muscles. In endotherm birds, cell metabolic efficiency can be tuned by the rate of mitochondrial coupling. Thus, avUCP may be a key contributor to controlling metabolic rate during particular environmental changes. METHODS: This study aimed to perform a set of in-silico investigations primarily focused on the structural, biological, and biomimetic functions of avUCP. Thereby, using in silico genome analyses among 8 avian species (chicken, turkey, swallow, manakin, sparrow, wagtail, pigeon, and mallard) and a series of bioinformatic approaches, we provide phylogenetic inference and comparative genomics of avUCPs and investigate whether sequence variation can alter coding sequence characteristics, the protein structure, and its biological features. Complementarily, a combination of literature mining and prediction approaches was also applied to predict the gene networks of avUCP to identify genes, pathways, and biological crosstalk associated with avUCP function. RESULTS: The results showed the evolutionary alteration of UCP proteins in different avian species. Uncoupling proteins in avian species are highly conserved trans membrane proteins as seen by sequence alignment, physio-chemical parameters, and predicted protein structures. Taken together, avUCP has the potential to be considered a functional marker for the identification of cell metabolic state, thermogenesis, and oxidative stress caused by cold, heat, fasting, transfer, and other chemical stimuli stresses in birds. It can also be deduced that avUCP, in migrant or domestic birds, may increase heat stress resistance by reducing fatty acid transport/b-oxidation and thermoregulation alongside antioxidant defense mechanisms. The predicted gene network for avUCP highlighted a cluster of 21 genes involved in response to stress and 28 genes related to lipid metabolism and the proton buffering system. Finally, among 11 enriched pathways, crosstalk of 5 signaling pathways including MAPK, adipocytokine, mTOR, insulin, ErbB, and GnRH was predicted, indicating a possible combination of positive or negative feedback among pathways to regulate avUCP functions. DISCUSSION: Genetic selection for fast-growing commercial poultry has unintentionally increased susceptibility to many kinds of oxidative stress, and so avUCP could be considered as a potential candidate gene for balancing energy expenditure and reactive oxygen species production, especially in breeding programs. In conclusion, avUCP can be introduced as a pleiotropic gene that requires the contribution of regulatory genes, hormones, pathways, and genetic crosstalk to allow its finely-tuned function

Investigations of antiproliferative and antioxidant activity of β-lactam morpholino-1,3,5-triazine hybrids

TARAMAPUBMEDTARAMASCOPUSTARAMAWOSThis article reports for the first time the synthesis of some novel β-lactam morpholino-1,3,5-triazine hybrids by a [2+2]-cycloaddition reaction of imines 7a–c, 9a–c and 11 with ketenes derived from substituted acetic acids. The reaction was totally diastereoselective, leading exclusively to the formation of cis-β-lactams 8a–l, 10a–f and 12a–c. The synthesized compounds were tested for activity towards SW1116, MCF-7 and HepG2 cancer cell lines and non-cancerous HEK-293 cell line by MTT assay. None of the compounds exert an observable effect on HepG2, MCF-7 and HEK-293 cells, but compounds 7b, 8f, 8g, 8l, 10c, and 10e exhibited excellent growth inhibitory activity (IC50 7b > 8f > 8g. Collectively, the in vitro capabilities of some of these morpholino-triazine imines and β- lactams suggest possible applications to development of new antioxidants and DNA binding therapeutics.Şiraz Üniversitesi (96-GR-SC-23