Tomatidine provides mitophagy-independent neuroprotection after ischemic injury,FEBS Open Bio

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Tomatidine provides mitophagy-independent neuroprotection after ischemic injury
FEBS Open Bio ( IF 2.8 ) Pub Date : 2021-08-04 , DOI: 10.1002/2211-5463.13265
Yu-Ting Wang ₁ , Li-Na Zhang ₁ , Xiao-Cui Lyu ₁ , Yue Li ₂ , Anil Ahsan ₂ , Zikai Feng ₂ , Xiangnan Zhang ₂

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Cerebral ischemia is one of the leading causes of human mortality and disability worldwide. The treatment of cerebral ischemia is refractory due to its short therapeutic window and lack of effective clinical drugs. Mitophagy, the autophagic elimination of damaged mitochondria, attenuates neuronal injury in cerebral ischemia, indicating the potential of mitophagy inducers as therapies for cerebral ischemia. We previously determined that, by enhancing autophagy flux, the steroidal alkaloid tomatidine can function as a neuroprotective agent against ischemic injury. However, its effects on mitophagy remain unknown. For this purpose, neuroblastoma cell lines Neuro-2a and SH-SY5Y were subjected to ischemic injury induced by oxygen–glucose deprivation/reperfusion (OGD/R) and then treated with tomatidine. OGD/R induced a general decrease of cellular contents, and this study revealed that tomatidine had no impact on mitophagy. In addition, tomatidine did not affect mitochondrial contents, including translocase of outer mitochondrial membrane 20 and voltage-dependent anion channel 1, in either OGD/R-treated or intact SH-SY5H cells. Our results indicate that tomatidine exhibits its neuroprotective effects by enhancing autophagy, but in a potentially mitophagy-independent manner, and provide insights for further investigation into its mechanism(s) and potential therapeutic use against cerebral ischemia.

中文翻译：

托马替丁在缺血性损伤后提供不依赖线粒体自噬的神经保护

脑缺血是全世界人类死亡和残疾的主要原因之一。由于治疗窗短且临床缺乏有效药物，脑缺血的治疗难度较大。线粒体自噬，即受损线粒体的自噬消除，可减轻脑缺血中的神经元损伤，表明线粒体自噬诱导剂作为脑缺血疗法的潜力。我们之前确定，通过增强自噬通量，类固醇生物碱番茄碱可以作为针对缺血性损伤的神经保护剂。然而，它对线粒体自噬的影响仍然未知。为此，神经母细胞瘤细胞系 Neuro-2a 和 SH-SY5Y 受到氧糖剥夺/再灌注 (OGD/R) 诱导的缺血性损伤，然后用番茄碱处理。 OGD/R 诱导细胞内容物普遍减少，这项研究表明番茄碱对线粒体自噬没有影响。此外，在 OGD/R 处理或完整的 SH-SY5H 细胞中，番茄碱不影响线粒体内容物，包括线粒体外膜 20 的转位酶和电压依赖性阴离子通道 1。我们的结果表明，番茄碱通过增强自噬来发挥其神经保护作用，但以一种潜在的线粒体自噬无关的方式，并为进一步研究其机制和针对脑缺血的潜在治疗用途提供了见解。

更新日期：2021-09-01

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