Inactivation of p38 kinase delays the onset of senescence in rabbit articuilar chondrocytes
Inactivation of p38 kinase delays the onset of senescence in rabbit articuilar chondrocytes
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DOI：
10.1016/j.mad.2004.11.009
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发表时间：
2005-05-01
影响因子：
5.3
通讯作者：
Shin, DY
中科院分区：
文献类型：
--
作者：
Kang, S;Jung, MS;Shin, DY
复制性衰老限制了体内和体外的细胞增殖。最近，其他研究小组和我们报道了p38激酶在衰老的发生中起关键作用。在这项研究中，我们证明了复制性衰老可以在体外兔软骨细胞中通过p38激酶失活来延迟。我们发现，p38激酶的活性在衰老的软骨细胞相比，衰老前的同行升高。为了研究p38激酶在衰老发生中的作用，我们使用化学抑制剂SB 203580或MKK6和p38的显性失活突变体形式（分别为MKK6A和p38dn）来灭活该激酶。我们发现，p38激酶的失活导致增殖的刺激，寿命的延长，并在衰老的发病延迟，从而意味着p38激酶限制兔关节软骨细胞在体外的寿命。(c)2004爱思唯尔爱尔兰有限公司保留所有权利。
Replicative senescence limits cellular proliferation in vivo and in vitro. Recently, other groups and we reported that p38 kinase plays a key role on the onset of senescence. In this study, we demonstrated that replicative senescence can be delayed in rabbit chondrocytes in vitro by that p38 kinase inactivation. We found that the activity of p38 kinase is elevated in senescent chondrocytes as compared to pre-senescent counterparts. To examine the role of p38 kinase on the onset of senescence, we inactivated the kinase pharmacologically or genetically using either a chemical inhibitor, SB203580, or dominant negative mutant forms of MKK6 and p38 (MKK6A and p38dn, respectively). We show that the inactivation of p38 kinase leads to the stimulation of proliferation, the extension of life span, and a delay in the onset of senescence, thus implying that p38 kinase limits the life span of rabbit articular chondrocytes in vitro. (c) 2004 Elsevier Ireland Ltd. All rights reserved.