Stress-induced autonomic dysregulation of mitochondrial function in the rat urothelium.
Stress-induced autonomic dysregulation of mitochondrial function in the rat urothelium.
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DOI：
10.1002/nau.23876
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发表时间：
2019-03
影响因子：
2
通讯作者：
Birder LA
中科院分区：
文献类型：
--
作者：
Kullmann FA;McDonnell BM;Wolf-Johnston AS;Kanai AJ;Shiva S;Chelimsky T;Rodriguez L;Birder LA
慢性压力会加剧大多数疼痛疾病的症状，包括间质性膀胱炎/膀胱疼痛综合征 (IC/BPS)。在这种使膀胱衰弱的情况下，尿路上皮细胞 (UTC) 会出现异常。可能将压力（可能通过交感神经系统-SNS 活动增加）与尿路上皮功能障碍联系起来的事件顺序尚不清楚。由于自主神经失调、线粒体功能障碍和氧化应激都发生在慢性疼痛中，因此我们研究了慢性心理压力是否引发了将这三种功能障碍联系起来的级联反应。成年雌性 Wistar京都大鼠经历 10 天的回避水应激 (WAS)。然后收获膀胱用于 UTC 培养物中的蛋白质印迹和单细胞成像。 WAS 大鼠的 UTC 表现出去极化线粒体膜电位（与对照相比，Ψm 去极化多约 30%）、激活的 AMPK 和改变的 UT 线粒体生物能学。粘膜中融合蛋白 mitofusion-2 (MFN-2) 的表达上调，表明线粒体结构变化与细胞代谢的改变一致。在培养的 WAS UTC 中，细胞内钙水平升高，这与细胞功能受损一致。用α-肾上腺素能 (α-AR) 受体激动剂刺激培养的 UTC 会增加活性氧化物质 (ROS) 的产生，表明 SNS 活性对 UTC 具有直接作用。用胍乙啶治疗大鼠以阻断 SNS 活性可阻止大部分 WAS 引起的变化。慢性压力会导致持续的交感神经介导效应，从而改变 UTC 线粒体功能。这可能会影响尿路上皮屏障和信号传导，从而导致膀胱功能障碍和疼痛。据我们所知，这是首次证明潜在的自主机制将压力与线粒体功能障碍直接联系起来。
Chronic stress exacerbates the symptoms of most pain disorders including interstitial cystitis/bladder pain syndrome (IC/BPS). Abnormalities in urothelial cells (UTC) occur in this debilitating bladder condition. The sequence of events that might link stress (presumably through increased sympathetic nervous system-SNS activity) to urothelial dysfunction are unknown. Since autonomic dysregulation, mitochondrial dysfunction, and oxidative stress all occur in chronic pain, we investigated whether chronic psychological stress initiated a cascade linking these three dysfunctions. Adult female Wistar Kyoto rats were exposed to 10 days of water avoidance stress (WAS). Bladders were then harvested for Western blot and single cell imaging in UTC cultures. UTC from WAS rats exhibited depolarized mitochondria membrane potential (Ψm ~30% more depolarized compared to control), activated AMPK and altered UT mitochondria bioenergetics. Expression of the fusion protein mitofusion-2 (MFN-2) was upregulated in the mucosa, suggesting mitochondrial structural changes consistent with altered cellular metabolism. Intracellular calcium levels were elevated in cultured WAS UTC, consistent with impaired cellular function. Stimulation of cultured UTC with alpha-adrenergic (α-AR) receptor agonists increased reactive oxidative species (ROS) production, suggesting a direct action of SNS activity on UTC. Treatment of rats with guanethidine to block SNS activity prevented most of WAS-induced changes. Chronic stress results in persistent sympathetically mediated effects that alter UTC mitochondrial function. This may impact the urothelial barrier and signaling, which contributes to bladder dysfunction and pain. This is the first demonstration, to our knowledge, of a potential autonomic mechanism directly linking stress to mitochondrial dysfunction.
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DOI：
10.1523/jneurosci.5369-07.2008
发表时间：
2008-03-05
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Andersson DA;Gentry C;Moss S;Bevan S
通讯作者：
Bevan S
影响因子：
2.7
作者：
Birder, Lori A.
通讯作者：
Birder, Lori A.
影响因子：
5.9
作者：
Hanno, Philip;Nordling, Jorgen;Fall, Magnus
通讯作者：
Fall, Magnus
靶向线粒体的抗氧化剂可保留老年大鼠骨骼肌的收缩特性和线粒体功能。
影响因子：
--
作者：
Javadov S;Jang S;Rodriguez-Reyes N;Rodriguez-Zayas AE;Soto Hernandez J;Krainz T;Wipf P;Frontera W
通讯作者：
Frontera W
影响因子：
2
作者：
Charrua, Ana;Pinto, Rui;Cruz, Francisco
通讯作者：
Cruz, Francisco