Hypoxic induction of UCP3 in the growth plate: UCP3 suppresses chondrocyte autophagy.
Hypoxic induction of UCP3 in the growth plate: UCP3 suppresses chondrocyte autophagy.
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DOI：
10.1002/jcp.21408
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发表时间：
2008-08
影响因子：
5.6
通讯作者：
Shapiro, Irving M.
中科院分区：
文献类型：
--
作者：
Watanabe, Hitoshi;Bohensky, Jolene;Freeman, Theresa;Srinivas, Vickram;Shapiro, Irving M.
这项研究的总体目标是研究解偶联蛋白(UCP)在调控软骨细胞成熟过程中的晚期事件中的作用。我们首次发现了骨痂软骨细胞表达UCP3。缺氧时，UCP3对线粒体跨膜电位(Δψm)的调节依赖于HIF-1α。我们还首次展示了UCP3调控自噬的诱导。因此，抑制UCP3增强了自噬表型的表达，即使在血清充足的培养液中也是如此。可以预见的是，成熟的自噬软骨细胞容易受到凋亡素的挑战。易感性可能与胞浆中抗凋亡蛋白bcl2和bclxL的表达降低以及细胞色素c的基线表达升高有关。我们的结论是，与缺氧诱导因子-1α相一致，UCP3通过调节跨膜电位来调节线粒体的活性。此外，它还抑制自噬反应的诱导。当这种情况发生时，它会抑制对促进软骨细胞从生长板上删除的药物的敏感性。
The overall goal of the investigation was to examine the role of uncoupling proteins (UCP’s) in regulating late stage events in the chondrocyte maturation pathway. We showed for the first time that epiphyseal chondrocytes expressed UCP3. In hypoxia, UCP3 mediated regulation of the mitochondrial transmembrane potential (Δψm) was dependent on HIF-1α. We also showed for the first time that UCP3 regulated the induction of autophagy. Thus, suppression of UCP3 enhanced the expression of the autophagic phenotype, even in serum-replete media. Predictably, the mature autophagic chondrocytes were susceptible to an apoptogen challenge. Susceptibility was probably associated with a lowered expression of the anti-apoptotic proteins Bcl2 and BCLxL and a raised baseline expression of cytochrome c in the cytosol. We conclude that in concert with HIF-1α, UCP3 regulates the activity of the mitochondrion by modulating the transmembrane potential. In addition, it suppresses induction of the autophagic response. When this occurs, it suppresses sensitivity to agents that promote chondrocyte deletion from the growth plate.
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影响因子：
56.9
作者：
SHAPIRO, IM;GOLUB, EE;FRASCA, P
通讯作者：
FRASCA, P
影响因子：
4.8
作者：
Adams, CS;Mansfield, K;Shapiro, IM
通讯作者：
Shapiro, IM
线粒体解偶联蛋白。
影响因子：
12.3
作者：
Ledesma A;de Lacoba MG;Rial E
通讯作者：
Rial E
影响因子：
13.3
作者：
Bohensky, Jolene;Shapiro, Irving M.;Srinivas, Vickram
通讯作者：
Srinivas, Vickram
影响因子：
29
作者：
Kim, JW;Tchernyshyov, I;Dang, CV
通讯作者：
Dang, CV