Detection and quantification of 10-formyltetrahydrofolate dehydrogenase (10-FTHFDH) in rat retina,optic nerve,and brain |
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| Affiliation: | 1. Department of Ophthalmology, National Health Insurance Service Ilsan Hospital, Goyang, South Korea;2. Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, South Korea;3. Valued-Eye Clinic, Daejeon, South Korea;4. Department of Ophthalmology, Korea University College of Medicine, Seoul, South Korea;5. Institute of Vascular Disease and Metabolism, Yonsei University College of Medicine, Seoul, South Korea;6. College of Pharmacy, Yonsei University, Seoul, South Korea;1. Department of Microbiology, Yokohama City University School of Medicine, Kanagawa, 236-0004, Japan;2. Life Science Laboratory, Technology and Development Division, Kanto Chemical Co., Inc., Kanagawa, 259-1146, Japan;3. Division of Virology, Kawasaki City Institute for Public Health, Kanagawa, 210-0821, Japan;4. Department of Health Science, Gunma Paz University Graduate School, Gunma, 370-0006, Japan;5. Influenza Research Center, National Institute of Infectious Diseases, Tokyo, 208-0011, Japan;1. Keio University School of Medicine, Tokyo, Japan;2. Kyoto Prefectural University of Medicine, Kyoto, Japan;3. Tokyo Dental College, Ichikawa, Japan;4. Kansai Rosai Hospital, Amagasaki, Japan;5. Kyorin University School of Medicine, Tokyo, Japan;6. Korea University Anam Hospital, Korea;7. Ulsan University Asan Medical Center, Korea;8. Seoul National University, Seoul National University Bundang Hospital, Korea;9. Chonnam National University Hospital, Korea;10. Yonsei University Severance Hospital, Korea;11. Beijing Tongren Eye Center, Beijing Institute of Ophthalmology, China;12. The Affiliated Eye Hospital of Wenzhou Medical University, China;13. Zhongshan Ophthalmic Center, Sun Yat-Sen University, China;14. Peking University People''s Hospital, China;15. Eye Institute of Xiamen University, China;1. The Key Laboratory for Human Disease Gene Study of Sichuan Province, Department of Clinical Laboratory, Sichuan Provincial People''s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, PR China;2. Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences, Sichuan Academy of Medical Sciences, Chengdu, Sichuan 610072, PR China;3. Department of Ophthalmology, Sichuan Provincial People''s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, PR China;4. Institute of Chengdu Biology, Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, Sichuan 610041, PR China;1. QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia;2. Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia;3. Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victorian, Australia;4. School of Medicine, Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia;5. Lions Eye Institute, Centre for Ophthalmology and Visual Science, University of Western Australia, Perth, Western Australia, Australia |
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| Abstract: | Methanol poisoning is characterized by the accumulation of formic acid, a metabolite of methanol, which can lead to metabolic acidosis and ocular toxicity. Formate metabolism to CO2 is governed by tissue H4folate and 10-FTHFDH levels. Presumably, rats are not normally susceptible to formate toxicity because they possess high hepatic H4folate and 10-FTHFDH levels. However, the ability of target tissues to metabolize formate is not known. Therefore, studies were performed to determine whether 10-FTHFDH was present in rat retina, optic nerve, and brain. 10-FTHFDH levels were determined using Western blot analysis of mitochondiral and postmitochondrial preparations from these tissues. Hepatic mitochandrial and postmitochondrial levels of 10-FTHFDH were 13 and 12 ng/μg protein, respectively. Postmitochondrial levels of 10-FTHFDH in rat retina, optic nerve and whole brain were 0.2, 1.3, and 2.1 ng/μg protein; mitochondrial values in retina and brain were 0.2 and 1.5 ng/μg protein, respectively. Postmitochondrial values obtained for rat brain regions were similar to those found for whole brain. These results suggest that, in rats, target tissues possess the capacity to metabolize formate to CO2 and may be protected from formate toxicity through this folate-dependent system. |
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