Heterogeneous basal expression of nitric oxide synthase and superoxide dismutase isoforms in mammalian heart - Implications for mechanisms governing indirect and direct nitric oxide-related effects
Heterogeneous basal expression of nitric oxide synthase and superoxide dismutase isoforms in mammalian heart - Implications for mechanisms governing indirect and direct nitric oxide-related effects
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DOI：
10.1161/01.res.85.7.575
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发表时间：
1999-10-01
影响因子：
20.1
通讯作者：
Campbell, DL
中科院分区：
文献类型：
--
作者：
Brahmajothi, MV;Campbell, DL
通过免疫荧光定位法测定雪貂心脏（组织切片和分离的心肌细胞）中NO合酶（NOS;内皮型[eNOS]、神经型[nNOS]和精氨酸诱导型[iNOS]）和超氧化物歧化酶（SOD;细胞外膜结合型[ECSOD]、MnSOD和CuZnSOD）亚型的基础表达模式。本研究首次在哺乳动物心脏中发现：（1）eNOS和ECSOD在不同组织和不同心肌细胞中的异质性表达，（2）eNOS和ECSOD在组织和心肌细胞水平上的共定位，（3）eNOS和ECSOD在心肌细胞中的共定位，（4）eNOS和ECSOD在心肌细胞中的共定位。（3）eNOS和ECSOD在左室壁的表达呈明显的梯度变化，这两种酶在左心室心外膜肌细胞中高度表达和共定位，但在左心室内膜肌细胞中显著降低;（4）eNOS和3种SOD同工型的特异性亚细胞定位模式。特别是，eNOS和ECSOD被证明（电子显微镜和共聚焦显微镜）是专门定位于心室肌细胞的肌膜，类似的异质性eNOS和ECSOD的表达模式，也获得了人类LV组织切片，强调了这些新的发现的普遍重要性。我们的数据表明，肌膜定位的心肌细胞eNOS和ECSOD的活性在控制NO中有很强的功能相关性。O-2（-）的相互作用，并表明NO相关的心肌细胞蛋白和/或离子通道功能的调节作用可能比目前认为的要复杂得多。
The basal expression patterns of NO synthase (NOS; endothelial [eNOS], neuronal [nNOS], and cytokine-inducible [iNOS]) and superoxide dismutase (SOD; extracellular membrane bound [ECSOD], MnSOD, and CuZnSOD) isoforms in ferret heart (tissue sections and isolated myocytes) were determined by immunofluorescent localization. We demonstrate the following for the first time in the mammalian heart: (1) heterogeneous expression patterns of the 3 NOS and 3 SOD isoforms among different tissue and myocyte types; (2) colocalization of eNOS and ECSOD at both the tissue and myocyte levels; (3) a significant gradient of eNOS and ECSOD expression across the left ventricular (LV) wall, with both enzymes being highly expressed and colocalized in LV epicardial myocytes but markedly reduced in LV endocardial myocytes; and (4) specific subcellular localization patterns of eNOS and the 3 SOD isoforms. In particular, eNOS and ECSOD are demonstrated (electron and confocal microscopy) to be specifically localized to the sarcolemma of ventricular myocytes, Similar heterogeneous eNOS and ECSOD expression patterns were also obtained in human LV tissue sections, underscoring the general importance of these novel findings. Our data suggest a strong functional correlation between the activities of sarcolemmally localized myocyte eNOS and ECSOD in governing NO./O-2(-) interactions and suggest that NO-related modulatory effects on cardiac myocyte protein and/or ion channel function may be significantly more complex than is presently believed.