The neutral cysteine protease bleomycin hydrolase is essential for epidermal integrity and bleomycin resistance
| العنوان: | The neutral cysteine protease bleomycin hydrolase is essential for epidermal integrity and bleomycin resistance |
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| المؤلفون: | John S. Lazo, Dale G. Hoyt, Donald R. Schwartz, John Abernethy, Gregg E. Homanics, Ed Klein |
| المصدر: | Proceedings of the National Academy of Sciences. 96:4680-4685 |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 1999. |
| سنة النشر: | 1999 |
| مصطلحات موضوعية: | Aging, Restriction Mapping, Drug Resistance, Dermatitis, Biology, Bleomycin, Mice, chemistry.chemical_compound, Pulmonary fibrosis, medicine, Animals, Humans, Skin, Mice, Knockout, chemistry.chemical_classification, Multidisciplinary, Acrodermatitis enteropathica, Bleomycin hydrolase, Gene targeting, Biological Sciences, medicine.disease, Molecular biology, Cysteine protease, In vitro, Cysteine Endopeptidases, Enzyme, Animals, Newborn, chemistry, Biochemistry, Epidermis |
| الوصف: | The papain superfamily member bleomycin hydrolase (Blmh) is a neutral cysteine protease with structural similarity to a 20S proteasome. Bleomycin (BLM), a clinically used glycopeptide anticancer agent, is deaminated in vitro by Blmh. We used gene targeting to generate mice that lack Blmh and demonstrated that Blmh is the sole enzyme required for BLM deamination. Although some Blmh null mice were viable and reproduced, only about 65% of the expected number survived the neonatal period, revealing an important role for Blmh in neonatal survival. Mice lacking Blmh exhibited variably penetrant tail dermatitis that resembled rodent ringtail. The histopathology of the tail dermatitis was similar to skin lesions in humans with pellagra, necrolytic migratory erythema, and acrodermatitis enteropathica. Compared with controls, Blmh null mice were more sensitive to acute BLM lethality and developed pulmonary fibrosis more readily following BLM treatment. Thus, we have established that Blmh is an essential protectant against BLM-induced death and has an important role in neonatal survival and in maintaining epidermal integrity. |
| تدمد: | 1091-6490 0027-8424 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2db555785162c0d17702697afe6a607b https://doi.org/10.1073/pnas.96.8.4680 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....2db555785162c0d17702697afe6a607b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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