کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5892260 | 1153302 | 2010 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The resorptive apparatus of osteoclasts supports lysosomotropism and increases potency of basic versus non-basic inhibitors of cathepsin K
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شناسی تکاملی
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چکیده انگلیسی
Next, we compared the ability of basic and non-basic inhibitors of catK to suppress bone resorption by human osteoclasts. We found that basic compounds were considerably more potent than non-basic compounds at suppression of osteoclastic resorption than would be anticipated from their potency as enzyme inhibitors. Also consistent with osteoclastic lysosomotropism, basic inhibitors suppressed resorption for substantially longer than a non-basic inhibitor after washout from cell cultures. Furthermore, selectivity of basic inhibitors for inhibition of catK versus other cathepsins persisted: concentrations that inhibited catK in osteoclasts had no detectable effect on cathepsin S (catS) in a cell-based assay. This data is consistent with accumulation and enrichment of such basic inhibitors in the resorptive apparatus of the osteoclast, allowing for prolonged efficacy at the intended site of action. Our results suggest a major advantage for lysosomotropic compounds as inhibitors of bone resorption by osteoclasts in osteoporosis and other diseases caused by excessive osteoclastic activity.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bone - Volume 46, Issue 5, May 2010, Pages 1400-1407
Journal: Bone - Volume 46, Issue 5, May 2010, Pages 1400-1407
نویسندگان
Karen Fuller, Erik Lindstrom, Michael Edlund, Ian Henderson, Urszula Grabowska, Kinga A. Szewczyk, Raymond Moss, Bertil Samuelsson, Timothy J. Chambers,