LKB1 is the gatekeeper of carotid body chemosensing and the hypoxic ventilatory response.
LKB1 is the gatekeeper of carotid body chemosensing and the hypoxic ventilatory response.
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DOI：
10.1038/s42003-022-03583-7
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发表时间：
2022-06-29
影响因子：
5.9
通讯作者：
中科院分区：
文献类型：
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作者：
低氧通气反应（HVR）对呼吸和机体供氧至关重要，主要由颈动脉体介导。在这里，我们揭示了缺氧和高碳血症时颈动脉体传入放电是由肝激酶B1 （LKB1）的表达决定的，肝激酶B1是代谢应激时激活amp活化蛋白激酶（AMPK）的主要激酶。相反，AMPK儿茶酚胺能细胞的条件性缺失对颈动脉机体对缺氧或高碳酸血症的反应没有影响。相比之下，LKB1和AMPK的缺失使HVR减弱。然而，在LKB1敲除中，缺氧引起通气不足、呼吸暂停和cheyne - stokes样呼吸，而AMPK缺失后仅观察到通气不足和呼吸暂停。因此，我们确定LKB1是颈动脉体化学感应的重要调节因子，并发现颈动脉体和HVR对LKB1和AMPK的依赖性存在差异。与AMPK不同，肝激酶B1 （LBK1）是颈动脉体化学感应和缺氧通气反应所必需的。此外，LBK1而非AMPK的缺失会在缺氧时引发cheyne - stokes样呼吸，这与心力衰竭有关。
The hypoxic ventilatory response (HVR) is critical to breathing and thus oxygen supply to the body and is primarily mediated by the carotid bodies. Here we reveal that carotid body afferent discharge during hypoxia and hypercapnia is determined by the expression of Liver Kinase B1 (LKB1), the principal kinase that activates the AMP-activated protein kinase (AMPK) during metabolic stresses. Conversely, conditional deletion in catecholaminergic cells of AMPK had no effect on carotid body responses to hypoxia or hypercapnia. By contrast, the HVR was attenuated by LKB1 and AMPK deletion. However, in LKB1 knockouts hypoxia evoked hypoventilation, apnoea and Cheyne-Stokes-like breathing, while only hypoventilation and apnoea were observed after AMPK deletion. We therefore identify LKB1 as an essential regulator of carotid body chemosensing and uncover a divergence in dependency on LKB1 and AMPK between the carotid body on one hand and the HVR on the other. Unlike AMPK, Liver kinase B1 (LBK1) is required for carotid body chemosensing and the hypoxic ventilatory response. Moreover, loss of LBK1, but not AMPK, provokes Cheyne-Stokes-like breathing during hypoxia, which is associated with heart failure.
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影响因子：
29
作者：
Gowans GJ;Hawley SA;Ross FA;Hardie DG
通讯作者：
Hardie DG
影响因子：
--
作者：
Hawley SA;Boudeau J;Reid JL;Mustard KJ;Udd L;Mäkelä TP;Alessi DR;Hardie DG
通讯作者：
Hardie DG
影响因子：
3.3
作者：
Hirooka, Y;Polson, JW;Dampney, RAL
通讯作者：
Dampney, RAL
影响因子：
11.4
作者：
Boudeau, J;Baas, AF;Alessi, DR
通讯作者：
Alessi, DR
影响因子：
64.8
作者：
通讯作者：
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