ALDA WAKAMATSU

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LIM/14 - Laboratório de Investigação em Patologia Hepática, Hospital das Clínicas, Faculdade de Medicina

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Revista / Livro: American Journal of Pathology ×

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  • article 107 Citação(ões) na Scopus
    Age-Related Dysfunction of the Lacrimal Gland and Oxidative Stress Evidence from the Cu,Zn-Superoxide Dismutase-1 (Sod1) Knockout Mice
    (2012) KOJIMA, Takashi; WAKAMATSU, Tais H.; DOGRU, Murat; OGAWA, Yoko; IGARASHI, Ayako; IBRAHIM, Osama M. A.; INABA, Takaaki; SHIMIZU, Takahiko; NODA, Setsuko; OBATA, Hiroto; NAKAMURA, Shigeru; WAKAMATSU, Alda; SHIRASAWA, Takuji; SHIMAZAKI, Jun; NEGISHI, Kazuno; TSUBOTA, Kazuo
    An imbalance between free radical generation and radical scavenging antioxidant systems results in oxidative stress, which has been associated with cell Injury observed in many age-related diseases. The superoxide dismutase (SOD) family is a major antioxidant system, and deficiency of Cu,Zn-superoxide dismutase-1 (Sod1) in mice leads to many different phenotypes that resemble accelerated aging. In this study we examined the morphologic features and the secretory functions of the lacrimal glands in Sod1(-/-) mice. Lacrimal glands showed atrophy of acinar units; fibrosis; infiltration with CD4(+) T cells, monocytes, and neutrophils; increased staining with both 4-hydroxy-2-nonenal and 8-hydroxy-2'-deoxyguanosine; increases in apoptotic cells; and the presence of the epithelial-mesenchymal transition in senescent Sod1(-/-) mice. Electron microscopy findings revealed evidence of epithelial-mesenchymal transition, presence of swollen and degenerated mitochondria, and the presence of apoptotic cell death in the lacrimal glands of senescent Sod1(-/-) mice. These alterations were also associated with the accumulation of secretory vesicles in acinar epithelial cells, decreased production of both stimulated and nonstimulated tears, and a decline in total protein secretion from the lacrimal glands. Our results suggest that Sod1(-/-) mice may be a good model system in which to study the mechanism of reactive oxygen species-mediated lacrimal gland alterations. (Am J Pathol 2012, 180: 1879 1 89 4 DOI: 10.1016/j.ajpath.201201.019)