ABSTRACT
Polyphosphates have been found in all cell types examined to date and play diverse roles depending on the cell type. In eukaryotic organisms, polyphosphates have been investigated mainly in mammalian cells, and only a few studies have addressed arthropods. Pyrophosphatases have been shown to regulate polyphosphate metabolism. However, these studies were restricted to trypanosomatids. Here we focus on the tick Rhipicephalus microplus, a haematophagous ectoparasite that is highly harmful to cattle. We produced a recombinant R. microplus pyrophosphatase (rRmPPase) with the aim of investigating its kinetic parameters using polyphosphates as substrate. Molecular docking assays of RmPPase with polyphosphates were also carried out. The kinetic and Hill coefficient parameters indicated that rRmPPase has a greater affinity, higher catalytic efficiency and increased cooperativity for sodium phosphate glass type 15 (polyP15 ) than for sodium tripolyphosphate (polyP3 ). Through molecular docking, we found that polyP3 binds close to the Mg2+ atoms in the catalytic region of the protein, participating in their coordination network, whereas polyP15 interactions involve negatively charged phosphate groups and basic amino acid residues, such as Lys56, Arg58 and Lys193; polyP15 has a more favourable theoretical binding affinity than polyP3 , thus supporting the kinetic data. This study shows, for the first time in arthropods, a pyrophosphatase with polyphosphatase activity, suggesting its participation in polyphosphate metabolism.
Subject(s)
Arthropod Proteins/genetics , Inorganic Pyrophosphatase/genetics , Polyphosphates/metabolism , Rhipicephalus/genetics , Animals , Arthropod Proteins/metabolism , Hydrolysis , Inorganic Pyrophosphatase/metabolism , Molecular Docking Simulation , Rhipicephalus/enzymology , Rhipicephalus/metabolismABSTRACT
Diabetes mellitus is a serious health problem that can lead to several pathological complications in numerous organs and tissues. The most important and most prevalent organs affected by this disease are the heart and the kidneys, and these complications are the major causes of death in patients with diabetes. MicroRNAs (miRNAs), short non-coding RNAs, have been found to be functionally important in the regulation of several pathological processes, and they are emerging as an important therapeutic tool to avoid the complications of diabetes mellitus. This review summarizes the knowledge on the effects of miRNAs in diabetes. The use of miRNAs in diabetes from a clinical perspective is also discussed, focusing on their potential role to repair cardiovascular and renal complications.
Subject(s)
Diabetic Cardiomyopathies/therapy , Diabetic Retinopathy/therapy , Genetic Therapy/methods , Kidney/metabolism , MicroRNAs/metabolism , Myocardium/metabolism , Animals , Diabetic Cardiomyopathies/genetics , Diabetic Cardiomyopathies/metabolism , Diabetic Retinopathy/genetics , Diabetic Retinopathy/metabolism , Gene Expression Regulation , Genetic Markers , Humans , Oligonucleotides, Antisense/therapeutic use , RNA InterferenceABSTRACT
Entomopathogenic bacteria isolated from Simulium larvae and adults from breeding sites in the states of São Paulo and Rio de Janeiro, Brazil, were identified as 18 strains of Bacillus thuringiensis and one of B. sphaericus. Most of these strains were serotyped according to their flagellar antigens. However, nine of the B. thuringiensis samples, could not be serotyped and were designated as "autoagglutinating"; they were also shown to be toxic in preliminary tests against Aedes aegypti larvae. Additionally, B. sphaericus was also shown to be toxic towards Culex quinquefasciatus larvae.