Bafilomycin A1 Attenuates Osteoclast Acidification and Formation, Accompanied by Increased Levels of SQSTM1/p62 Protein
| Autor: | Jennifer Tickner, Haotian Feng, Taksum Cheng, Thomas Ratajczak, Nathan J. Pavlos, Huazi Xu, Sipin Zhu, John P. Walsh, Jiake Xu, Sarah L. Rea |
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| Rok vydání: | 2015 |
| Předmět: |
musculoskeletal diseases
0301 basic medicine Osteoclasts Biochemistry Negative regulator Mice 03 medical and health sciences chemistry.chemical_compound Osteoclast Sequestosome-1 Protein medicine Animals Humans Amines Enzyme Inhibitors Molecular Biology Cells Cultured Cell fusion Bafilomycin Protein level Cell Differentiation Cell Biology Cell biology RAW 264.7 Cells 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation chemistry Calcium Macrolides Intracellular |
| Zdroj: | Journal of Cellular Biochemistry. 117:1464-1470 |
| ISSN: | 1097-4644 0730-2312 |
| DOI: | 10.1002/jcb.25442 |
| Popis: | Vacuolar proton pump H(+)-adenosine triphosphatases (V-ATPases) play an important role in osteoclast function. Further understanding of the cellular and molecular mechanisms of V-ATPase inhibition is vital for the development of anti-resorptive drugs specifically targeting osteoclast V-ATPases. In this study, we observed that bafilomycin A1, a naturally-occurring inhibitor of V-ATPases, increased the protein level of SQSTM1/p62, a known negative regulator of osteoclast formation. Consistently, we found that bafilomycin A1 diminishes the intracellular accumulation of the acidotropic probe lysotracker in osteoclast-like cells; indicative of reduced acidification. Further, bafilomycin A1 inhibits osteoclast formation with attenuation of cell fusion and multi-nucleation of osteoclast-like cells during osteoclast differentiation. Taken together, these data indicate that bafilomycin A1 attenuates osteoclast differentiation in part via increased levels of SQSTM1/p62 protein, providing further mechanistic insight into the effect of V-ATPase inhibition in osteoclasts. |
| Databáze: | OpenAIRE |
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