Gotoh Tomomi, Mori Masataka
Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Kumamoto 860-8556, Japan.
Arterioscler Thromb Vasc Biol. 2006 Jul;26(7):1439-46. doi: 10.1161/01.ATV.0000223900.67024.15. Epub 2006 Apr 27.
Nitric oxide (NO) is a multifunctional biomolecule involved in a variety of physiological and pathological processes, including regulation of blood vessel dilatation and anti-arteriosclerotic effects. However, a large amount of NO is toxic to the host and causes several diseases such as apoptosis, septic shock, and diabetes mellitus. Inducible-form NO synthase is induced in inflammatory diseases, including insulitis and arteriosclerosis. Endoplasmic reticulum (ER) stress pathway was first identified as a cellular response pathway induced by the accumulation of unfolded proteins in ER to preserve ER functions. Later it was found that ER stress pathway is also activated by various cellular stresses to protect cells, but when stresses are severe, apoptosis is induced to remove damaged cells. It is reported that NO and reactive oxygen species disturb ER functions, then ER stress-mediated apoptosis pathway is activated. CHOP/GADD153, which belongs to C/EBP transcription factor family, is induced in this process and mediates apoptosis. ER stress pathway induced by NO can be involved in the pathogenesis of various vascular diseases.
一氧化氮（NO）是一种多功能生物分子，参与多种生理和病理过程，包括调节血管舒张和抗动脉粥样硬化作用。然而，大量的NO对宿主有毒，并导致多种疾病，如细胞凋亡、脓毒症休克和糖尿病。诱导型一氧化氮合酶在包括胰岛炎和动脉硬化在内的炎症性疾病中被诱导产生。内质网（ER）应激途径最初被确定为一种细胞反应途径，由内质网中未折叠蛋白的积累所诱导，以维持内质网功能。后来发现，内质网应激途径也被各种细胞应激激活以保护细胞，但当应激严重时，会诱导细胞凋亡以清除受损细胞。据报道，NO和活性氧会干扰内质网功能，进而激活内质网应激介导的细胞凋亡途径。CHOP/GADD153属于C/EBP转录因子家族，在此过程中被诱导并介导细胞凋亡。由NO诱导的内质网应激途径可能参与各种血管疾病的发病机制。
