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一氧化氮合酶依赖性“开/关”开关和淡水和夏眠肺鱼,Protopterus annectens 的细胞凋亡:骨骼肌与心肌。

Nitric oxide synthase-dependent "on/off" switch and apoptosis in freshwater and aestivating lungfish, Protopterus annectens: skeletal muscle versus cardiac muscle.

机构信息

Department of Cell Biology, University of Calabria, 87030 Arcavacata di Rende, CS, Italy.

出版信息

Nitric Oxide. 2013 Aug 1;32:1-12. doi: 10.1016/j.niox.2013.03.005. Epub 2013 Mar 30.

DOI:10.1016/j.niox.2013.03.005
PMID:23545405
Abstract

African lungfishes (Protopterus spp.) are obligate air breathers which enter in a prolonged torpor (aestivation) in association with metabolic depression, and biochemical and morpho-functional readjustments during the dry season. During aestivation, the lungfish heart continues to pump, while the skeletal muscle stops to function but can immediately contract during arousal. Currently, nothing is known regarding the orchestration of the multilevel rearrangements occurring in myotomal and myocardial muscles during aestivation and arousal. Because of its universal role in cardio-circulatory and muscle homeostasis, nitric oxide (NO) could be involved in coordinating these stress-induced adaptations. Western blotting and immunofluorescence microscopy on cardiac and skeletal muscles of Protopterus annectens (freshwater, 6months of aestivation and 6days after arousal) showed that expression, localization and activity of the endothelial-like nitric oxide synthase (eNOS) isoform and its partners Akt and Hsp-90 are tissue-specifically modulated. During aestivation, phospho-eNOS/eNOS and phospho-Akt/Akt ratios increased in the heart but decreased in the skeletal muscle. By contrast, Hsp-90 increased in both muscle types during aestivation. TUNEL assay revealed that increased apoptosis occurred in the skeletal muscle of aestivating lungfish, but the myocardial apoptotic rate of the aestivating lungfish remained unchanged as compared with the freshwater control. Consistent with the preserved cardiac activity during aestivation, the expression of apoptosis repressor (ARC) also remained unchanged in the heart of aestivating and aroused fish as compared with the freshwater control. Contrarily, ARC expression was strongly reduced in the skeletal muscle of aestivating lungfish. On the whole, our data indicate that changes in the eNOS/NO system and cell turnover are implicated in the morpho-functional readjustments occurring in lungfish cardiac and skeletal muscle during the switch from freshwater to aestivation, and between the maintenance and arousal phases of aestivation.

摘要

非洲肺鱼(Protopterus spp.)是专性空气呼吸器,它们在旱季会与代谢抑制、生化和形态功能的重新调整相关联,进入长时间的休眠(夏眠)状态。在休眠期间,肺鱼的心脏继续跳动,而骨骼肌停止活动,但在苏醒时可以立即收缩。目前,对于休眠和苏醒过程中发生在肌节和心肌中的多层次重排,人们还一无所知。由于一氧化氮(NO)在心血管和肌肉稳态中的普遍作用,它可能参与协调这些应激诱导的适应。对淡水、休眠 6 个月和苏醒后 6 天的非洲肺鱼(Protopterus annectens)心脏和骨骼肌进行 Western blot 和免疫荧光显微镜分析显示,内皮型一氧化氮合酶(eNOS)同工型及其伴侣 Akt 和 Hsp-90 的表达、定位和活性在组织上是有特异性调节的。在休眠期间,心脏中的磷酸化 eNOS/eNOS 和磷酸化 Akt/Akt 比值增加,而骨骼肌中的比值则降低。相比之下,Hsp-90 在两种肌肉类型中均在休眠期间增加。TUNEL 检测显示,休眠肺鱼的骨骼肌中凋亡增加,但与淡水对照组相比,休眠肺鱼的心肌凋亡率保持不变。与休眠期间心脏活动保持不变一致的是,与淡水对照组相比,休眠和苏醒鱼类的心脏中的凋亡抑制因子(ARC)表达也保持不变。相反,休眠肺鱼骨骼肌中的 ARC 表达明显降低。总的来说,我们的数据表明,eNOS/NO 系统和细胞更新的变化可能与肺鱼心脏和骨骼肌在从淡水到休眠以及在休眠的维持和苏醒阶段之间的形态和功能重新调整有关。

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