Hypoxia induces cellular oxidative stress that is associated with neurodegenerative diseases. HPN (4'-hydroxyl-2-substituted phenyl nitronyl nitroxide), a stable nitronyl nitroxide, has excellent free radical scavenging properties. The purpose of this study was to investigate the protective effects of HPN on hypoxia-induced damage in PC12 cells. It was shown that HPN significantly attenuated hypoxia-induced loss of cell viability, release of lactate dehydrogenase (LDH), and morphological changes in PC12 cells. Moreover, hypoxic PC12 cells had increased levels of reactive oxygen species (ROS), malondialdehyde (MDA), and expression of HIF-1α and VEGF, but had reduced levels of superoxide dismutase (SOD) and catalase (CAT), and HPN reversed these changes. HPN also inhibited hypoxia-induced cell apoptosis via suppressing the expression of Bax, cytochrome c, and caspase-3, and inducing the expression of Bcl-2. These results indicate that the protective effects of HPN on hypoxia-induced damage in PC12 cells is associated with the suppression of hypoxia-induced oxidative stress and cell apoptosis. HPN could be a promising candidate for the development of a novel neuroprotective agent.

中文翻译：

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硝酰基氮氧化物对 PC12 细胞缺氧引起的损伤的保护作用。

缺氧会诱发与神经退行性疾病相关的细胞氧化应激。HPN（4'-羟基-2-取代苯基硝基硝基氧）是一种稳定的硝基氧，具有优异的自由基清除性能。本研究的目的是探讨 HPN 对缺氧引起的 PC12 细胞损伤的保护作用。结果表明，HPN 可显着减轻缺氧引起的细胞活力丧失、乳酸脱氢酶 (LDH) 的释放以及 PC12 细胞的形态变化。此外，缺氧的 PC12 细胞的活性氧 (ROS)、丙二醛 (MDA) 水平以及 HIF-1α 和 VEGF 表达增加，但超氧化物歧化酶 (SOD) 和过氧化氢酶 (CAT) 水平降低，HPN 逆转了这些情况变化。HPN 还通过抑制 Bax、细胞色素 c 和 caspase-3 的表达以及诱导 Bcl-2 的表达来抑制缺氧诱导的细胞凋亡。这些结果表明HPN对缺氧引起的PC12细胞损伤的保护作用与抑制缺氧引起的氧化应激和细胞凋亡有关。HPN 可能是开发新型神经保护剂的有希望的候选者。