Study on the dose-effect relationship and mechanism of reactive oxygen species promoted neuroprotection

doi:10.5246/jcps.2024.01.005

Abstract

Abstract:

The overproduction of reactive oxygen species (ROS) is widely acknowledged as a pivotal factor in the occurrence of ischemic stroke injuries. While numerous experimental studies have demonstrated the significant neuroprotective effects of antioxidants, their long-term clinical efficacy has consistently fallen short of expectations. Interestingly, ROS can exert positive physiological effects, such as promoting cell proliferation, activating protective autophagy, and enhancing antioxidant capacity, at certain concentrations. Consequently, preserving the advantageous aspects of ROS is crucial for addressing the limitations of antioxidant therapy. This study investigated the impact of ROS at varying concentrations on physiological and pathological functions, including neural cell proliferation, autophagy, and apoptosis. We also assessed the fluctuations in intracellular and mitochondrial ROS levels and delineated the dose range within which these advantageous functions occur. Additionally, we conducted further research using autophagy inhibitors and signaling pathway inhibitors. The findings demonstrated that 100 μM H₂O₂ could induce protective autophagy through HIF-1α and TFEB signaling pathways mediated by AKT/m-TOR, thereby conferring a protective effect on nerve cells. This study elucidated the concentration range at which ROS exerted a protective role and unraveled its neuroprotective mechanism, offering a crucial reference for optimizing the comprehensive application of antioxidants following cerebral ischemia.

Key words: Reactive oxygen species, Cerebral ischemia, Protective autophagy, HIF-1α, TFEB

Supporting:

Rong Huang, Xiaojiao Hu, Runfang Zhang, Xiaohui Li, Juan Cen. Study on the dose-effect relationship and mechanism of reactive oxygen species promoted neuroprotection[J]. Journal of Chinese Pharmaceutical Sciences, 2024, 33(1): 46-56.

Figures/Tables 8

References 24

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