Cigarette smoke (CS) and nicotine delay neutrophil spontaneous death via suppressing production of diphosphoinositol pentakisphosphate
Cigarette smoke (CS) and nicotine delay neutrophil spontaneous death via suppressing production of diphosphoinositol pentakisphosphate
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香烟烟雾（CS）和尼古丁通过抑制二磷酸肌醇五磷酸的产生来延迟中性粒细胞自发死亡
DOI：
10.1073/pnas.1302906110
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发表时间：
2013-04
影响因子：
11.1
通讯作者：
Luo, Hongbo R.
中科院分区：
文献类型：
--
作者：
Zhou, Yuan;Zhu, Haiyan;Ye, Keqiang;Luo, Hongbo R.
二磷酸肌醇五磷酸（InsP 7），一种含有高能焦磷酸键的高级肌醇磷酸，开始成为关键的细胞信号分子。然而，涉及InsP 7的各种生理和病理过程尚未完全了解。在这里，我们报告说，香烟烟雾（CS）提取物和尼古丁降低衰老中性粒细胞中的InsP 7水平。这随后导致Akt失活的抑制，Akt失活是中性粒细胞自发性死亡和迟发性中性粒细胞死亡的因果介质。CS提取物和尼古丁对中性粒细胞死亡的影响可以通过直接抑制PtdIns（3，4，5）P3/Akt通路或通过InsP 6 K1（一种负责中性粒细胞中InsP 7产生的肌醇六磷酸（InsP 6）激酶）的过表达来增加InsP 7水平来抑制。迟发性中性粒细胞死亡参与CS所致慢性阻塞性肺疾病的发病机制。因此，InsP 6 K1的破坏增加CS诱导的中性粒细胞积聚和肺损伤。总之，这些结果表明，CS和尼古丁通过抑制InsP 7的产生并因此阻断衰老中性粒细胞中Akt失活来延迟中性粒细胞的自发性死亡。通过这一途径调节中性粒细胞死亡为烟草诱导的慢性阻塞性肺疾病的治疗提供了策略和治疗靶点。
Diphosphoinositol pentakisphosphate (InsP7), a higher inositol phosphate containing energetic pyrophosphate bonds, is beginning to emerge as a key cellular signaling molecule. However, the various physiological and pathological processes that involve InsP7 are not completely understood. Here we report that cigarette smoke (CS) extract and nicotine reduce InsP7 levels in aging neutrophils. This subsequently leads to suppression of Akt deactivation, a causal mediator of neutrophil spontaneous death, and delayed neutrophil death. The effect of CS extract and nicotine on neutrophil death can be suppressed by either directly inhibiting the PtdIns(3,4,5)P3/Akt pathway, or increasing InsP7 levels via overexpression of InsP6K1, an inositol hexakisphosphate (InsP6) kinase responsible for InsP7 production in neutrophils. Delayed neutrophil death contributes to the pathogenesis of CS-induced chronic obstructive pulmonary disease. Therefore, disruption of InsP6K1 augments CS-induced neutrophil accumulation and lung damage. Taken together, these results suggest that CS and nicotine delay neutrophil spontaneous death by suppressing InsP7 production and consequently blocking Akt deactivation in aging neutrophils. Modifying neutrophil death via this pathway provides a strategy and therapeutic target for the treatment of tobacco-induced chronic obstructive pulmonary disease.
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影响因子：
7.3
作者：
Chakraborty A;Kim S;Snyder SH
通讯作者：
Snyder SH
影响因子：
64.5
作者：
Chakraborty A;Koldobskiy MA;Bello NT;Maxwell M;Potter JJ;Juluri KR;Maag D;Kim S;Huang AS;Dailey MJ;Saleh M;Snowman AM;Moran TH;Mezey E;Snyder SH
通讯作者：
Snyder SH
影响因子：
5.5
作者：
Iho, S;Tanaka, Y;Takahashi, T
通讯作者：
Takahashi, T
DOI：
10.3410/f.717967811.793467394
发表时间：
2013-01
期刊：
--
影响因子：
--
作者：
M. Welch;Rebecca L. Lamason
通讯作者：
M. Welch;Rebecca L. Lamason
DOI：
--
发表时间：
2005
期刊：
American journal of physiology. Lung cellular and molecular physiology
影响因子：
--
作者：
E. Finkelstein;J. Ruben;C. Koot;Milena Hristova;A. van der Vliet
通讯作者：
E. Finkelstein;J. Ruben;C. Koot;Milena Hristova;A. van der Vliet