Heme oxygenase-1 regulates cell proliferation via carbon monoxide-mediated inhibition of T-type Ca2+ channels.
Heme oxygenase-1 regulates cell proliferation via carbon monoxide-mediated inhibition of T-type Ca2+ channels.
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DOI：
10.1007/s00424-014-1503-5
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发表时间：
2015-02
影响因子：
4.5
通讯作者：
Peers, Chris
中科院分区：
文献类型：
--
作者：
Duckles, Hayley;Boycott, Hannah E.;Al-Owais, Moza M.;Elies, Jacobo;Johnson, Emily;Dallas, Mark L.;Porter, Karen E.;Giuntini, Francesca;Boyle, John P.;Scragg, Jason L.;Peers, Chris
抗氧化酶血红素加氧酶-1（HO-1）的诱导提供细胞保护并抑制与各种病理性心血管疾病（包括心肌梗死和血管损伤）相关的血管平滑肌细胞（VSMC）的增殖。然而，其潜在机制尚未完全了解。与未转染的细胞相比，在HEK 293细胞中过表达Cav3.2 T型Ca 2+通道提高了基础[Ca 2 +]i并增加了增殖。通过诱导HO-1或将细胞暴露于HO-1产物一氧化碳（CO）（作为CO释放分子，CORM-3），增殖和[Ca 2 +]i水平降低至未转染细胞中观察到的水平。在主动脉VSMC系A7 r5，增殖也受到抑制诱导HO-1或暴露的细胞CO，和膜片钳记录表明，CO抑制T型（以及L型）Ca 2+电流在这些细胞。最后，在人大隐静脉平滑肌细胞中，T型通道抑制或HO-1诱导或CO暴露可减少增殖。T型通道阻断和HO-1诱导的作用是非相加的。总的来说，这些数据表明HO-1通过CO介导的T型Ca 2+通道抑制来调节增殖。这种信号传导途径提供了一种新的手段，通过这种手段可以治疗性地调节VSMC（和其他细胞）的增殖。
Induction of the antioxidant enzyme heme oxygenase-1 (HO-1) affords cellular protection and suppresses proliferation of vascular smooth muscle cells (VSMCs) associated with a variety of pathological cardiovascular conditions including myocardial infarction and vascular injury. However, the underlying mechanisms are not fully understood. Over-expression of Cav3.2 T-type Ca2+ channels in HEK293 cells raised basal [Ca2+]i and increased proliferation as compared with non-transfected cells. Proliferation and [Ca2+]i levels were reduced to levels seen in non-transfected cells either by induction of HO-1 or exposure of cells to the HO-1 product, carbon monoxide (CO) (applied as the CO releasing molecule, CORM-3). In the aortic VSMC line A7r5, proliferation was also inhibited by induction of HO-1 or by exposure of cells to CO, and patch-clamp recordings indicated that CO inhibited T-type (as well as L-type) Ca2+ currents in these cells. Finally, in human saphenous vein smooth muscle cells, proliferation was reduced by T-type channel inhibition or by HO-1 induction or CO exposure. The effects of T-type channel blockade and HO-1 induction were non-additive. Collectively, these data indicate that HO-1 regulates proliferation via CO-mediated inhibition of T-type Ca2+ channels. This signalling pathway provides a novel means by which proliferation of VSMCs (and other cells) may be regulated therapeutically.
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影响因子：
3
作者：
BOLTON, TB;MACKENZIE, I;AARONSON, PI
通讯作者：
AARONSON, PI
影响因子：
3.4
作者：
Lee, JH;Gomora, JC;Perez-Reyes, E
通讯作者：
Perez-Reyes, E
影响因子：
4.8
作者：
Gollasch, M;Haase, H;Haller, H
通讯作者：
Haller, H
影响因子：
4
作者：
Cribbs, Leanne L.
通讯作者：
Cribbs, Leanne L.
影响因子：
3.5
作者：
Chemin, J;Monteil, A;Lory, P
通讯作者：
Lory, P