INVESTIGATION OF INFLAMMATION ASSOCIATED CYP2E1 AND CYP1A1 EXPRESSION IN THE EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS MOUSE MODEL OF MULTIPLE SCLEROSIS

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2023-1-27

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Solak, Damla

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Multiple sclerosis (MS) is an autoimmune neurodegenerative disease which affects brain and spinal cord. Myelin which wraps around the axon and its progenitor cells, oligodendrocytes, are destroyed in this disease. This results in the loss of signal transmission which leads to axonal, and eventually neuronal loss. There are various symptoms of the disease such as unstable feelings, fatigue, visual disability, muscle spasms, and walking difficulties. The etiology of the disease is still in its infancy; however, genetic, environmental factors, and abnormal immune responses are known to play a role in the development of multiple sclerosis. Cytochrome P450, one of the members of monooxygenases, are the enzymes predominantly localized in the liver but also in lung, brain, and kidney. They have an essential role in the metabolism of drugs, other xenobiotics, and endogenous substrates and activation of the procarcinogens. CYP2E1 is the second highly expressed CYP450 enzyme in liver and is also found in brain. CYP1A1 is mainly localized in lung but also in the brain and liver. The expression of CYP450 enzymes varies under inflammatory conditions. Accordingly, the bioavailability of drugs and other exogenous and endogenous substrates that are metabolized by these enzymes will be equally affected. Therefore, as multiple sclerosis is an inflammatory neurodegenerative disorder, unique expression levels of these enzymes need to be examined in these conditions. The possible change in gene (mRNA) and protein expression of CYP2E1 and CYP1A1 enzymes in liver and brain in the case of MS has not been investigated before. In this study, female C57BL/6 mouse model for experimental autoimmune encephalomyelitis (EAE - MS Model) was used to investigate the effects of EAE on mRNA and protein levels of CYP2E1 and CYP1A1 by qPCR and Western blotting techniques, respectively. The mRNA and the protein expression of the control group were equilibrated to 1.00 fold and the relative expression of the EAE group were estimated. The results of this study illustrate that the EAE immunization was not significantly affecting the mRNA and the protein levels of CYP2E1 and CYP1A1 in mice liver and brain. Nevertheless, protein expression of CYP2E1 is slightly higher in the EAE group compared to the control group. Moreover, CYP2E1 and CYP1A1 mRNA expressions were increased slightly in the liver of the EAE group and CYP2E1 mRNA expression was decreased slightly in the brain of EAE group compared to the control group, but the results were not statistically significant.

Subject Keywords

Multiple Sclerosis (MS), CYP2E1, CYP1A1, Experimental autoimmune encephalomyelitis (EAE), Brain, Liver, Mouse, Inflammation

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https://hdl.handle.net/11511/102503

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Graduate School of Natural and Applied Sciences, Thesis

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Citation Formats

D. Solak, “INVESTIGATION OF INFLAMMATION ASSOCIATED CYP2E1 AND CYP1A1 EXPRESSION IN THE EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS MOUSE MODEL OF MULTIPLE SCLEROSIS,” M.S. - Master of Science, Middle East Technical University, 2023.