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Article

Higher Blood Uric Acid in Female Humans and Mice as a Protective Factor against Pathophysiological Decline of Lung Function

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Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan
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Program for Leading Graduate Schools “HIGO (Health life science: Interdisciplinary and Global Oriented) Program”, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan
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Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan
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Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, 714 Petit Science Center, 100 Piedmont Ave SE, Atlanta, GA30303, USA
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Division of Reproductive Engineering, Center for Animal Resources and Development (CARD), Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860–0811, Japan
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Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan
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Japanese Red Cross Kumamoto Health Care Center, Kumamoto, 2-1-1 Nagamine-minami, Higashi-ku, Kumamoto 861-8520, Japan
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Human Physiology and Pathology, Faculty of Pharma-Science, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan
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Department of Pharmacy, The University of Tokyo Hospital, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
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Laboratory of Pharmacology, Division of Life Science, Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto 860-0082, Japan
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Global Center for Natural Resources Sciences, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-Honmachi, Chuo-ku, Kumamoto, 862-0973, Japan
*
Authors to whom correspondence should be addressed.
Antioxidants 2020, 9(5), 387; https://doi.org/10.3390/antiox9050387
Received: 23 March 2020 / Revised: 1 May 2020 / Accepted: 3 May 2020 / Published: 6 May 2020
The oxidant/antioxidant imbalance plays a pivotal role in the lung. Uric acid (UA), an endogenous antioxidant, is highly present in lung tissue, however, its impact on lung function under pathophysiological conditions remains unknown. In this work, pharmacological and genetic inhibition of UA metabolism in experimental mouse models of acute and chronic obstructive pulmonary disease (COPD) revealed that increased plasma UA levels improved emphysematous phenotype and lung dysfunction in accordance with reduced oxidative stress specifically in female but not in male mice, despite no impact of plasma UA induction on the pulmonary phenotypes in nondiseased mice. In vitro experiments determined that UA significantly suppressed hydrogen peroxide (H2O2)-induced oxidative stress in female donor-derived primary human bronchial epithelial (NHBE) cells in the absence of estrogen, implying that the benefit of UA is limited to the female airway in postmenopausal conditions. Consistently, our clinical observational analyses confirmed that higher blood UA levels, as well as the SLC2A9/GLUT9 rs11722228 T/T genotype, were associated with higher lung function in elderly human females. Together, our findings provide the first unique evidence that higher blood UA is a protective factor against the pathological decline of lung function in female mice, and possibly against aging-associated physiological decline in human females. View Full-Text
Keywords: oxidative stress; uric acid (UA); mice; lung function; sexual differences; elderly; SLC2A9/GLUT9; single nucleotide polymorphism (SNP) oxidative stress; uric acid (UA); mice; lung function; sexual differences; elderly; SLC2A9/GLUT9; single nucleotide polymorphism (SNP)
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MDPI and ACS Style

Fujikawa, H.; Sakamoto, Y.; Masuda, N.; Oniki, K.; Kamei, S.; Nohara, H.; Nakashima, R.; Maruta, K.; Kawakami, T.; Eto, Y.; Takahashi, N.; Takeo, T.; Nakagata, N.; Watanabe, H.; Otake, K.; Ogata, Y.; Tomioka, N.H.; Hosoyamada, M.; Takada, T.; Ueno-Shuto, K.; Suico, M.A.; Kai, H.; Saruwatari, J.; Shuto, T. Higher Blood Uric Acid in Female Humans and Mice as a Protective Factor against Pathophysiological Decline of Lung Function. Antioxidants 2020, 9, 387. https://doi.org/10.3390/antiox9050387

AMA Style

Fujikawa H, Sakamoto Y, Masuda N, Oniki K, Kamei S, Nohara H, Nakashima R, Maruta K, Kawakami T, Eto Y, Takahashi N, Takeo T, Nakagata N, Watanabe H, Otake K, Ogata Y, Tomioka NH, Hosoyamada M, Takada T, Ueno-Shuto K, Suico MA, Kai H, Saruwatari J, Shuto T. Higher Blood Uric Acid in Female Humans and Mice as a Protective Factor against Pathophysiological Decline of Lung Function. Antioxidants. 2020; 9(5):387. https://doi.org/10.3390/antiox9050387

Chicago/Turabian Style

Fujikawa, Haruka, Yuki Sakamoto, Natsuki Masuda, Kentaro Oniki, Shunsuke Kamei, Hirofumi Nohara, Ryunosuke Nakashima, Kasumi Maruta, Taisei Kawakami, Yuka Eto, Noriki Takahashi, Toru Takeo, Naomi Nakagata, Hiroshi Watanabe, Koji Otake, Yasuhiro Ogata, Naoko H. Tomioka, Makoto Hosoyamada, Tappei Takada, Keiko Ueno-Shuto, Mary A. Suico, Hirofumi Kai, Junji Saruwatari, and Tsuyoshi Shuto. 2020. "Higher Blood Uric Acid in Female Humans and Mice as a Protective Factor against Pathophysiological Decline of Lung Function" Antioxidants 9, no. 5: 387. https://doi.org/10.3390/antiox9050387

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