Deimination of the myelin basic protein decelerates its proteasome-mediated metabolism.
Deimination of myelin basic protein (MBP) by peptidylarginine deiminase (PAD) prevents its binding to the proteasome and decelerates its degradation by the proteasome in mammalian cells. Potential anticancer drug tetrazole analogue of chloramidine 2, at concentrations greater than 1 µM inhibits the enzymatic activity of PAD in vitro. The observed acceleration of proteasome hydrolysis of MBP to antigenic peptides in the presence of PAD inhibitor may increase the efficiency of lesion of the central nervous system by cytotoxic lymphocytes in multiple sclerosis. We therefore suggest that clinical trials and the introduction of PAD inhibitors in clinical practice for the treatment of malignant neoplasms should be performed only after a careful analysis of their potential effect on the induction of autoimmune neurodegeneration processes.
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow, 117997, Russia.
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Kuzina
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow, 117997, Russia.
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Kudriaeva
Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, ul. Karla Marksa 74, Kazan, 420055 Tatarstan, Russia.
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Glagoleva
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow, 117997, Russia. vera.knorre@gmail.com.
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Knorre
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow, 117997, Russia.|Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, ul. Karla Marksa 74, Kazan, 420055 Tatarstan, Russia.|Faculty of Chemistry, Moscow State University, Moscow, 119991, Russia.
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Gabibov
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow, 117997, Russia.|Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, ul. Karla Marksa 74, Kazan, 420055 Tatarstan, Russia.|Institute of Gene Biology, Russian Academy of Sciences, ul. Vavilova 34/5, Moscow, 119334, Russia.
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Belogurov
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D000069286:Bortezomib / Q000494:pharmacology; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D006867:Hydrolases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D006868:Hydrolysis; D008809:Mice, Inbred C3H; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000378:metabolism; D018482:Muscle, Skeletal / Q000201:enzymology; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D000076342:Protein-Arginine Deiminases; D059748:Proteolysis; D011817:Rabbits; D013777:Tetrazoles / Q000494:pharmacology*; D014162:Transfection
D001713:Biphenyl Compounds; D004791:Enzyme Inhibitors; D004676:Myelin Basic Protein; C000613746:N-(4-((2-chloroethanimidoyl)amino)-1-(2-tert-butyl-2H-tetrazol- 5-yl)butyl)biphenyl-4-carboxamide; D018696:Neuroprotective Agents; D013777:Tetrazoles; D000069286:Bortezomib; D006867:Hydrolases; D046988:Proteasome Endopeptidase Complex; D000076342:Protein-Arginine Deiminases