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不同条件下血红素加氧酶的调控及其与细胞凋亡和自噬的相互作用

Regulation of Heme Oxygenase and Its Cross-Talks with Apoptosis and Autophagy under Different Conditions in .

作者信息

Al L Abaquita Terence, Damulewicz Milena, Bhattacharya Debarati, Pyza Elżbieta

机构信息

Department of Cell Biology and Imaging, Institute of Zoology and Biomedical Research, Jagiellonian University, 30-387 Cracow, Poland.

出版信息

Antioxidants (Basel). 2021 Oct 28;10(11):1716. doi: 10.3390/antiox10111716.

Abstract

Heme oxygenase (HO) is one of the cytoprotective enzymes that can mitigate the effects of oxidative stress. Here, we found that the mRNA level oscillates in the brain of with two minima at the beginning of the day and night. This rhythm was partly masked by light as its pattern changed in constant darkness (DD). It followed a similar trend in the clock mutant under light/dark regime (LD12:12); however, differences between time points were not statistically significant. In older flies (20 days old), the rhythm was vanished; however, 15 days of curcumin feeding restored this rhythm with an elevated mRNA level at all time points studied. In addition, flies exposed to paraquat had higher expression in the brain, but only at a specific time of the day which can be a protective response of the brain against stress. These findings suggest that the expression of in the fly's brain is regulated by the circadian clock, light, age, exposure to stress, and the presence of exogenous antioxidants. We also found that HO cross-talks with apoptosis and autophagy under different conditions. Induction of neuronal was accompanied by increased transcription of apoptosis and autophagy-related genes. However, this trend changed after exposure to curcumin and paraquat. Our results suggest that HO is involved in the control of apoptotic and autophagic key processes protecting the brain against oxidative damage.

摘要

血红素加氧酶(HO)是一种能够减轻氧化应激影响的细胞保护酶。在此,我们发现其mRNA水平在果蝇大脑中呈振荡变化,在白天和夜晚开始时出现两个最低点。这种节律部分被光照掩盖,因为在持续黑暗(DD)条件下其模式发生了变化。在光/暗周期(LD12:12)下,时钟突变体中的情况遵循类似趋势;然而,各时间点之间的差异无统计学意义。在老龄果蝇(20日龄)中,这种节律消失了;然而,喂食姜黄素15天可恢复该节律,且在所研究的所有时间点,mRNA水平均升高。此外,接触百草枯的果蝇大脑中HO表达较高,但仅在一天中的特定时间,这可能是大脑对应激的一种保护反应。这些发现表明,果蝇大脑中HO的表达受昼夜节律时钟、光照、年龄、应激暴露以及外源性抗氧化剂的存在所调节。我们还发现,在不同条件下,HO与凋亡和自噬相互作用。神经元HO的诱导伴随着凋亡和自噬相关基因转录的增加。然而,在接触姜黄素和百草枯后,这种趋势发生了变化。我们的结果表明,HO参与调控凋亡和自噬关键过程,保护大脑免受氧化损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f02/8614956/f737637145ef/antioxidants-10-01716-g001.jpg

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