RESUMO
Phymorhynchus is a genus of deep-sea snails that are most distributed in hydrothermal vent or cold seep environments. In this study, we presented the complete mitochondrial genome of P. buccinoides, a cold seep snail from the South China Sea. It is the first mitochondrial genome of a cold seep member of the superfamily Conoidea. The mitochondrial genome is 15,764 bp in length, and contains 13 protein-coding genes (PCGs), 2 rRNA genes, and 22 tRNA genes. These genes are encoded on the positive strand, except for 8 tRNA genes that are encoded on the negative strand. The start codon ATG and 3 types of stop codons, TAA, TAG and the truncated termination codon T, are used in the 13 PCGs. All 13 PCGs in the 26 species of Conoidea share the same gene order, while several tRNA genes have been translocated. Phylogenetic analysis revealed that P. buccinoides clustered with Typhlosyrinx sp., Eubela sp., and Phymorhynchus sp., forming the Raphitomidae clade, with high support values. Positive selection analysis showed that a residue located in atp6 (18 S) was identified as the positively selected site with high posterior probabilities, suggesting potential adaption to the cold seep environment. Overall, our data will provide a useful resource on the evolutionary adaptation of cold seep snails for future studies.
Assuntos
Genoma Mitocondrial , Caramujos/genética , Animais , DNA Mitocondrial/genética , Ordem dos Genes , Genes Mitocondriais , Proteínas Mitocondriais/genética , Filogenia , RNA Ribossômico/genética , RNA de Transferência/genéticaRESUMO
Free Fatty Acid 4 receptor (FFA4 receptor or GPR120), a rhodopsin-like G protein coupled receptor (GPCR) subfamily member, is a receptor that senses specific fatty acids such as ω-3 fatty acid in fish oil or the endogenous signaling lipid, PHASA. FFA4 receptor is enriched in lung, colon and adipose tissue but is also detected in many other tissues and cells. The activation of FFA4 receptor has multiple effects, including but not limited to inhibition of inflammation, improving insulin sensitivity and adipogenesis, and regulating hormone secretion from the gastro-intestinal system and pancreatic islets. The important role of FFA4 receptor in maintaining metabolic homeostasis strongly indicates the great potential of selective FFA4 receptor agonizts to treat diabetes and inflammation. In this review, we summarize recent research progress in the physiological and biochemical studies of FFA4 receptor and highlight its underlying signaling mechanisms and ligand identification to assist future research to exploit FFA4 receptor as a drug target.
Assuntos
Descoberta de Drogas/métodos , Hipoglicemiantes/farmacologia , Terapia de Alvo Molecular/métodos , Receptores Acoplados a Proteínas G/metabolismo , Sequência de Aminoácidos , Animais , Arrestina/metabolismo , Humanos , Dados de Sequência Molecular , Receptores Acoplados a Proteínas G/química , Receptores Acoplados a Proteínas G/genética , Transdução de Sinais/efeitos dos fármacosRESUMO
Combined blockade of IKr and IKs potassium channels is considered to be a promising therapeutic strategy for arrhythmia. In this study, we designed and synthesized 15 derivatives through modifying the hit compound 7 that was discovered by screening in-house database by whole-patch clamp technique. All of the compounds were evaluated on CHO and HEK 293 cell lines stably expressing hERG (IKr) and hKCNQ1/KCNE1 (IKs) potassium channels, and half of them exhibited improved dual IKr and IKs inhibitory effects compared to the hit compound. Compounds 7a and 7b with potent dual inhibitory activities were selected for further in vivo evaluations. Due to the preferable pharmacological behaviors, compound 7a deserved further optimization as a promising lead compound.
