RESUMO
Grp1-associated scaffold protein (Grasp), the product of a retinoic acid-induced gene in P19 embryonal carcinoma cells, is expressed primarily in brain, heart, and lung of the mouse. We report herein that Grasp transcripts are also found in mouse skin in which the Grasp gene is robustly induced following acute ultraviolet-B (UVB) exposure. Grasp(-/-) mice were found to exhibit delayed epidermal proliferation and a blunted apoptotic response after acute UVB exposure. Immunohistochemical analyses revealed that the nuclear residence time of the tumor suppressor protein p53 was reduced in Grasp(-/-) mice after UVB exposure. Taken together, our results suggest that a physiological role of Grasp may be to regulate skin homeostasis after UVB exposure, potentially by influencing p53-mediated apoptotic responses in skin.
Assuntos
Proteínas de Transporte/metabolismo , Proteínas de Membrana/metabolismo , Fenômenos Fisiológicos da Pele/efeitos da radiação , Pele/efeitos da radiação , Animais , Apoptose/fisiologia , Apoptose/efeitos da radiação , Proteínas de Transporte/genética , Núcleo Celular/fisiologia , Núcleo Celular/efeitos da radiação , Proliferação de Células/efeitos da radiação , Células Cultivadas , Derme/fisiologia , Derme/efeitos da radiação , Epiderme/patologia , Epiderme/fisiologia , Epiderme/efeitos da radiação , Fibroblastos/fisiologia , Fibroblastos/efeitos da radiação , Homeostase/fisiologia , Homeostase/efeitos da radiação , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína Supressora de Tumor p53/metabolismo , Raios UltravioletaRESUMO
In 1948, a dynamic junior member of the Johns Hopkins Biology Department, William McElroy, became the first director of the McCollum-Pratt Institute for the Investigation of Micronutrient Elements. The Institute was founded at the university to further studies into the practicalities of animal nutrition. Ultimately, however, the Institute reflected McElroy's vision that all biological problems, including nutrition, could be best investigated through basic biochemical and enzyme studies. The Institute quickly became a hub of biochemical research over the following decade, producing foundational work on metabolism and a respected series of symposia. In this paper, I argue that McElroy's biochemical vantage on biology also permeated the traditionally morphological and embryological Biology Department at Hopkins. Largely due to the activity of McElroy and the Institute, the faculty, course offerings, and research underwent a radical reorientation toward biochemistry and molecular biology in the 1950s, even while maintaining a commitment to developmental biology. While the history of postwar biology is often told as the ascendancy of the "new" biology over "traditional" biology, the case of McElroy and the McCollum-Pratt Institute affords an opportunity for historical examination of biochemical and molecular science as a lens through which all branches of biology at an institution were reconceived and unified.