INVESTIGATION OF EFFECTS OF VITAMIN D AND VITAMIN D METABOLIZING CYP450 ISOZYMES ON MULTIPLE SCLEROSIS PATHOPHYSIOLOGY IN ANIMAL MODEL BY MOLECULAR APPROACHES

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2021-8

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Evin, Emre

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Multiple sclerosis (MS) is a complicated, recurrent, and often progressive inflammatory demyelinating autoimmune disease of the central nervous system, yet etiopathogenesis remains unsolved. MS frequency increases with increasing latitude, leading to a hypothesis that MS is inversely correlated with the duration and intensity of sunlight and vitamin D concentrations. In this study, the relationships between vitamin D supplementation, MS, VDR, and vitamin D metabolizing CYP enzymes, including CYP2R1, CYP27A1, CYP27B1, and CYP24A1 at mRNA and protein expression levels, were investigated by qRT-PCR and Western blotting techniques in female C57BL/6 mouse autoimmune encephalomyelitis (EAE) model. Both mRNA and protein expressions of Gr 1 were set to 1.00 fold, and expressions of the other groups were calculated relatively to Gr 1. At first, mice were divided into four groups; Gr 1 (control), Gr 2 (vitamin D supplemented control), Gr 3 (EAE), and Gr 4 (vitamin D supplemented EAE). According to the results of this study, vitamin D was not a preventive but a therapeutic agent since significantly higher numbers of mice were recovered in the Gr 4 (8 mice out of 12) than the Gr 3 (2 mice out of 12) (p=0.013<0.05). There was no statistically significant difference in CYP27A1 mRNA and protein expression among the groups. CYP2R1 mRNA expression was significantly low in Gr 4 (0.50 fold; p<0.05). However, CYP2R1 protein expression was not significantly different between the groups. CYP27B1 mRNA and protein expression were significantly high in Gr 2 and Gr 4 compared to Gr 3. CYP24A1 protein expression was higher in Gr 4 (1.70±0.46; p<0.05), which was positively correlated with the clinical score of the EAE. Although VDR mRNA expression increases with the EAE immunization, it was reverted in protein expression levels probably because of the post-transcriptional regulations by miRNAs. In conclusion, vitamin D supplementation and CYP24A1 inhibitor therapy may help to reduce the severity of MS symptoms.

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Vitamin D, Experimental autoimmune encephalomyelitis, VDR, Vitamin D metabolizing CYPs,, Multiple sclerosis

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https://hdl.handle.net/11511/91679

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Graduate School of Natural and Applied Sciences, Thesis

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Citation Formats

E. Evin, “INVESTIGATION OF EFFECTS OF VITAMIN D AND VITAMIN D METABOLIZING CYP450 ISOZYMES ON MULTIPLE SCLEROSIS PATHOPHYSIOLOGY IN ANIMAL MODEL BY MOLECULAR APPROACHES,” Ph.D. - Doctoral Program, Middle East Technical University, 2021.