ABSTRACT

          Background and Objective: Genetic variations in the gene encoding endothelial nitric oxide synthase (eNOS) enzyme affect the susceptibility to cardiovascular disease. Identification of the way these changes affect eNOS structure and function in laboratory conditions is difficult and time-consuming. Thus, it seems essential to perform bioinformatics studies prior to laboratory studies to find  the variants that are more important. This study aimed to predict the damaging effect of changes in the coding region of eNOS using homology- and structure-based algorithms (SIFT and PolyPhen).

           Methods: First, the single nucleotide polymorphisms in the coding region (cSNPs) of the human eNOS gene were extracted from dbSNP. Resulting amino acid changes were reported as primary data required for the study. Then, position and type of amino acid changes along with the complete amino acid sequence were separately entered into the SIFT and PolyPhen tools for analysis.

         Results: Of 144 single nucleotide changes, 38 changes by the SIFT, 47 changes by the PolyPhen and 18 amino acid substitutions by both tools were predicted as damaging.

          Conclusion: It is predicted that 18 amino acid changes may have damaging phenotypic effects on the structure of the eNOS enzyme that may affect its performance by potentially affecting the enzyme’s various functional regions. Therefore, computational prediction of potentially damaging nsSNPs and prioritizing amino acid changes may be useful for investigating protein performance using targeted re-sequencing and gene mutagenesis experiments.

        

Background and Objective: The cell division cycle 25 (CDC25)is a familyof highly conserved dual-specificity phosphatases that activate cyclin-dependent kinase complexes. These complexes are the main cell cycle regulators. Mammalian cells ,exposure to DNA damaging radiations such as ionizing radiation and ultraviolet light, prevent cell cycle progression by activation of checkpoint pathways and lead to cell death.

      Methods: In this study, mice were exposed to different doses of ionizing radiation. Their total cellular protein was extracted from the bone marrow. After determining and matching the protein concentrations, CDC25A phosphatase levels were measured by western blotting.

        Results: The results showed that exposure to different doses of ionizing radiation in vivo significantly increased the expression of CDC25A compared to control group (P <0.05).

        Conclusion: Exposure to ionizing radiation increases the expression of CDC25A phosphatase, which increases the possibility of tumorigenesis in that area by increasing bone marrow cell proliferation.

        Keywords: Cell Cycle, CDC25A, Ionizing Radiation, Cyclin-Dependent Kinase.

ABSTRACT
         Background and Objectives: Exposure to ionizing radiation in modern societies is inevitable and can cause a variety of adverse health effects such as cancer and birth defects. Therefore, a reliable, repeatable and sensitive method is required for evaluation of radiation exposure. The aim of this study was to determine the amount of histone H2AX phosphorylation as an indicator of radiation exposure to evaluate the rate of double-strand DNA breakage in irradiated mice.
         Methods: In this study, 15 mice were exposed to different doses of ionizing radiation. After extraction of total protein from bone marrow cells, γH2AX protein was measured by western blotting. Data analysis was performed using ANOVA, Tukey's post hoc test, and the Pearson's correlation test.
         Results: The amount of γH2AX protein in the exposed groups increased significantly compared to the control group (P<0.05).
        Conclusion: The results of this study indicate that exposure to ionizing radiation increases the amount of γH2AX protein in bone marrow cells during the early hours. The protein can be used as a biomarker for monitoring of acute radiation or suspected local radiation exposure.
        Keywords: γH2AX Protein, Ionizing Radiation, Mouse.