Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 1464–1470 |
| Journal | Journal of Cellular Biochemistry |
| Volume | 117 |
| Issue number | 6 |
| Early online date | 26 Nov 2015 |
| DOIs | |
| Publication status | Published - Jun 2016 |
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Bafilomycin A1 Attenuates Osteoclast Acidification and Formation, Accompanied by Increased Levels of SQSTM1/p62 Protein. / Zhu, Sipin; Rea, Sarah; Cheng, Tak Sum; Feng, Hao Tian; Walsh, John; Ratajczak, Tom; Tickner, Jennifer; Pavlos, Nathan; Xu, H; Xu, Jiake.
In: Journal of Cellular Biochemistry, Vol. 117, No. 6, 06.2016, p. 1464–1470.Research output: Contribution to journal › Article
TY - JOUR
T1 - Bafilomycin A1 Attenuates Osteoclast Acidification and Formation, Accompanied by Increased Levels of SQSTM1/p62 Protein
AU - Zhu, Sipin
AU - Rea, Sarah
AU - Cheng, Tak Sum
AU - Feng, Hao Tian
AU - Walsh, John
AU - Ratajczak, Tom
AU - Tickner, Jennifer
AU - Pavlos, Nathan
AU - Xu, H
AU - Xu, Jiake
PY - 2016/6
Y1 - 2016/6
N2 - 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. J. Cell. Biochem. 117: 1464–1470, 2016. © 2015 Wiley Periodicals, Inc.
AB - 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. J. Cell. Biochem. 117: 1464–1470, 2016. © 2015 Wiley Periodicals, Inc.
U2 - 10.1002/jcb.25442
DO - 10.1002/jcb.25442
M3 - Article
VL - 117
SP - 1464
EP - 1470
JO - Journal of Cellular Biochemistry
JF - Journal of Cellular Biochemistry
SN - 0730-2312
IS - 6
ER -