Carbon Monoxide Mediated Vascular Responses and Interactions with Other Gasotransmitters in Mouse Aorta
Project no. 20636 · Status: Kapanmış (Yayın bekleniyor) · 2019
Summary
Gasotransmitters are gaseous molecules that can be produced enzymatically at need, can penetrate through the plasma membrane by diffusion instead of receptor-ligand interaction and show their effects in a concentration-dependent manner with or without secondary messenger molecule. NO, H2S and CO signaling molecules are the molecules so far classified as gasotransmitters. The complex relation between gasotransmitters and their paradoxical effect on the cardiovascular system has created a new research area. Since the complex interactions between gasotransmitters are regulated by evolutionarily preserved enzymes, gasotransmitters have had their regulatory impact on different biological diseases since the beginning of time. Furthermore, the concentration-dependent mechanism of action of gasotransmitters makes their concentration and presence detection a point of interest. This study has mainly focused on CO gazaotransmitter; its effect on vascular tonus and its interaction with other gasotransmitters during this process. Also, this study reveals a new approch to determination of CO molecule via biosensors. The differences in the results of exogenous CO-induced vasodilation and maximum contraction obtained within the scope of the study clearly demonstrate the interaction with the NO gasotransmitter. The interaction between CO and H2S gasotransmitters was investigated using the combination of H2S precursor L-Cysteine, exogenous H2S donor NaHS and non-selective H2S inhibitor AOAA incubations with cumulative CORM-2 dose-response experiments. These results reveal that endothelium integrity plays a tremendous role in CO-induced vasodilation. Moreover, to investigate the effect of H2S gasotransmitter on basal CO production, heme-oxygenase inhibitor CrMP and CO precursor Hemin incubation applications were performed with the combination of NaHS and L-Cysteine cumulative dose-response experiments. As a consequence of this experiment, hemin incubation results increased vasodilation levels whereas CrMP incubation decreased these results. Moreover, studies have been carried out on the development of a biosensor for the detection of exogenously produced CO molecule by mimicking a naturally occurring enzymatic reaction based on a LC principle system. As a result, it has been achieved to detect CO with a simple LC system principle which is an optically observable biosensor based on enzyme-substrate-inhibitor relation. The interaction of the enzyme Cytochrome C Oxidase (COX), which functions as an ETS element during aerobic respiration in nature, with its substrate, cytochrome C, can be inhibited by blocking it by the CO molecule. The inhibition effect of the CO molecule on this ezimatic reaction was used. The biosensor determines CO based on inhibition on this basis. As a conclusion of this study, endothelial integrity plays a tremendously important role in CO gasotransmitter caused vasodilation. Furthermore, during this study, a novel method was developed to detect CO gasotransmitter based on an optical system that consists of LC and enzyme-substrate-inhibitor interaction.