Hyaluronic acid regulates a key redox control factor Nrf2 via phosphorylation of Akt in bovine articular chondrocytes.
Hyaluronic acid regulates a key redox control factor Nrf2 via phosphorylation of Akt in bovine articular chondrocytes.
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DOI：
10.1016/j.fob.2015.05.007
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发表时间：
2015
期刊：
影响因子：
2.6
通讯作者：
Fukuda, Kanji
中科院分区：
文献类型：
--
作者：
Onodera, Yuta;Teramura, Takeshi;Takehara, Toshiyuki;Fukuda, Kanji
关键词：
透明质酸（HA）具有减少细胞超氧化物的药理作用。在HA处理的软骨细胞中，Nrf 2及其下游基因的表达上调。抑制Akt或抑制HA受体可阻止HA介导的Nrf 2积累。Nrf 2 siRNA抑制HA对抗氧化酶的作用。HA可能通过激活Akt调节Nrf 2来减少ROS。透明质酸（HA）在软骨细胞中的一个重要药理学功能是减少细胞超氧化物的产生和积累。在这里，我们证明了HA的补充和积累的核因子-红细胞-2-相关因子2（Nrf 2），这是一个主转录因子在细胞氧化还原反应，在培养的软骨细胞来源于牛关节软骨之间的关系。在HA处理的软骨细胞中，Nrf 2及其下游基因的表达上调。在HA处理的软骨细胞中，Akt被磷酸化，并且用siRNA抑制Akt活性或抑制HA受体CD 44和/或RHAMM阻止HA介导的Nrf 2积累。此外，Nrf 2 siRNA抑制了HA对抗氧化酶的影响。这些结果表明，HA可能通过激活Akt，通过Nrf 2调节而有助于ROS减少。我们的研究提示了软骨细胞中细胞外基质（ECM）介导的氧化还原系统的新机制。
Hyaluronic acid (HA) has a pharmacological role for reduction of cellular superoxide. In HA-treated chondrocytes, expression of Nrf2 and its downstream genes was upregulated. Inhibition of Akt or suppression of HA receptors prevented HA-mediated Nrf2 accumulation. Nrf2 siRNA inhibited the HA effect on antioxidant enzymes. HA might contribute to ROS reduction through Nrf2 regulation by activating Akt. One important pharmacological function of hyaluronic acid (HA) in chondrocytes is reduction of cellular superoxide generation and accumulation. Here we demonstrated a relationship between HA supplementation and accumulation of Nuclear factor-erythroid-2-related factor 2 (Nrf2), which is a master transcription factor in cellular redox reactions, in cultured chondrocytes derived from bovine joint cartilage. In HA-treated chondrocytes, expression of Nrf2 and its downstream genes was upregulated. In HA-treated chondrocytes, Akt was phosphorylated, and inhibition of Akt activity or suppression of HA receptors CD44 and/or RHAMM with siRNAs prevented HA-mediated Nrf2 accumulation. Furthermore, Nrf2 siRNA inhibited the HA effect on antioxidant enzymes. These results show that HA might contribute to ROS reduction through Nrf2 regulation by activating Akt. Our study suggests a new mechanism for extracellular matrix (ECM)-mediated redox systems in chondrocytes.
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DOI：
10.1097/01.blo.0000143804.26638.82
发表时间：
2004-10-01
影响因子：
4.2
作者：
Knudson, CB;Knudson, W
通讯作者：
Knudson, W
影响因子：
120.1
作者：
Drummond, Grant R.;Selemidis, Stavros;Griendling, Kathy K.;Sobey, Christopher G.
通讯作者：
Sobey, Christopher G.
影响因子：
9
作者：
Kudoh K;Uchinami H;Yoshioka M;Seki E;Yamamoto Y
通讯作者：
Yamamoto Y
影响因子：
10.5
作者：
Jaramillo MC;Zhang DD
通讯作者：
Zhang DD
影响因子：
5.2
作者：
Johnson, Jeffrey A.;Johnson, Delinda A.;Kraft, Andrew D.;Calkins, Marcus J.;Jakel, Rebekah J.;Vargas, Marcelo R.;Chen, Pei-Chun
通讯作者：
Chen, Pei-Chun