Higher Blood Uric Acid in Female Humans and Mice as a Protective Factor against Pathophysiological Decline of Lung Function
| Autor: | Yasuhiro Ogata, Junji Saruwatari, Yuka Eto, Yuki Sakamoto, Naomi Nakagata, Hirofumi Kai, Tsuyoshi Shuto, Mary Ann Suico, Natsuki Masuda, Tappei Takada, Keiko Ueno-Shuto, Taisei Kawakami, Toru Takeo, Makoto Hosoyamada, Ryunosuke Nakashima, Hirofumi Nohara, Kasumi Maruta, Haruka Fujikawa, Hiroshi Watanabe, Naoko H. Tomioka, Kentaro Oniki, Koji Otake, Shunsuke Kamei, Noriki Takahashi |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Antioxidant mice Physiology medicine.drug_class medicine.medical_treatment Clinical Biochemistry 030204 cardiovascular system & hematology medicine.disease_cause Biochemistry elderly Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine single nucleotide polymorphism (SNP) Internal medicine medicine oxidative stress Molecular Biology COPD Lung biology business.industry lcsh:RM1-950 lung function Cell Biology respiratory system medicine.disease Pathophysiology 030104 developmental biology Endocrinology medicine.anatomical_structure lcsh:Therapeutics. Pharmacology chemistry Estrogen biology.protein uric acid (UA) Uric acid SLC2A9/GLUT9 business Oxidative stress SLC2A9 sexual differences |
| Zdroj: | Antioxidants, Vol 9, Iss 387, p 387 (2020) Antioxidants Volume 9 Issue 5 |
| ISSN: | 2076-3921 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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