Essential role of hemoglobin beta-93-cysteine in posthypoxia facilitation of breathing in conscious mice
Essential role of hemoglobin beta-93-cysteine in posthypoxia facilitation of breathing in conscious mice
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DOI：
10.1152/japplphysiol.01050.2013
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发表时间：
2014-05-01
影响因子：
3.3
通讯作者：
Lewis, Stephen J.
中科院分区：
文献类型：
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作者：
Gaston, Benjamin;May, Walter J.;Lewis, Stephen J.
当红细胞血红蛋白(Hb)被O-2完全饱和时，一氧化氮(NO)与Hbβ链上的半胱氨酸93残基(B93-Cys)共价结合，形成S亚硝基血红蛋白。NO的结合与Hb的O-2饱和度是变构偶联的。随着饱和度的降低，B93-CyS上的NO基团转移到红细胞中的硫醇和血浆中，形成循环的S-亚硝硫醇。在这里，我们研究了暴露在低氧刺激期间和之后的换气变化是否依赖于红细胞B93-Cys。研究是在清醒的小鼠中进行的，其中用人Hb取代天然小鼠Hb(hB93-Cys小鼠)，以及在B链第93位用含有丙氨酸而不是半胱氨酸的人Hb取代小鼠Hb(hB93-Ala)。这两个菌株都表达人类伽马链Hb，可能允许残留S亚硝硫醇依赖的信号转导元件。HB93-Cys小鼠和hB93-Ala小鼠的静息参数和初始低氧(10%O-2，90%N-2)呼吸反应相似，但hB93-Ala小鼠返回室内空气后的兴奋性呼吸反应(短时增强)明显减弱。此外，在双侧切断颈动脉窦神经的小鼠中，短期增强反应几乎是不存在的。这些数据表明，hB93-Cys在介导颈动脉窦神经依赖的短时程增强中起重要作用，这是急性缺氧恢复的重要机制。
When erythrocyte hemoglobin (Hb) is fully saturated with O-2, nitric oxide (NO) covalently binds to the cysteine 93 residue of the Hb beta-chain (B93-CYS), forming S-nitrosohemoglobin. Binding of NO is allosterically coupled to the O-2 saturation of Hb. As saturation falls, the NO group on B93-CYS is transferred to thiols in the erythrocyte, and in the plasma, forming circulating S-nitrosothiols. Here, we studied whether the changes in ventilation during and following exposure to a hypoxic challenge were dependent on erythrocytic B93-CYS. Studies were performed in conscious mice in which native murine Hb was replaced with human Hb (hB93-CYS mice) and in mice in which murine Hb was replaced with human Hb containing an alanine rather than cysteine at position 93 on the Bchain (hB93-ALA). Both strains expressed human gamma-chain Hb, likely allowing a residual element of S-nitrosothiol-dependent signaling. While resting parameters and initial hypoxic (10% O-2, 90% N-2) ventilatory responses were similar in hB93-CYS mice and hB93-ALA mice, the excitatory ventilatory responses (short-term potentiation) that occurred once the mice were returned to room air were markedly diminished in hB93-ALA mice. Further, short-term potentiation responses were virtually absent in mice with bilateral transection of the carotid sinus nerves. These data demonstrate that hB93-CYS plays an essential role in mediating carotid sinus nerve-dependent short-term potentiation, an important mechanism for recovery from acute hypoxia.