Remote ischemic postconditioning attenuates damage in rats with chronic cerebral ischemia by upregulating the autophagolysosome pathway via the activation of TFEB.

Abstract

The transcription factor EB (TFEB) is known for its role in lysosomal biogenesis, and it coordinates this process by driving autophagy and lysosomal gene expression during ischemia. In the present study, we aimed to explore the role of the TFEB-regulated autophagolysosome pathway (ALP) in rats with chronic cerebral ischemia (CCI) that were treated with remote ischemic postconditioning (RIPC). A modified 2-vessel occlusion (2-VO) method was utilized to establish the CCI rat model, and the CCI rats were identified by the Morris water maze test and histological staining. After the CCI rats were treated with RIPC, the damage to the rat cortex and hippocampal tissues and the status of the ALP were determined. Western blot analysis and immunofluorescence assays were performed to observe the nuclear translocation of TFEB. The rats were injected with TFEB siRNA via the lateral ventricle to investigate the effect of TFEB siRNA on the RIPC-treated CCI rats. The results suggested that RIPC of the CCI rats alleviated nerve injury, induced TFEB translocation into the nucleus, upregulated autophagy-related protein expression, and activated ALP machinery. Furthermore, TFEB siRNA decreased the levels of TFEB and impaired the neuroprotective effects of RIPC on the CCI rats. Collectively, we highlighted that RIPC attenuates damage in CCI rats via the activation of the TFEB-mediated ALP.

• Authors: Zhiwei Li, Xiaoli Cui, Hua Lv, Jun Liu, Wei Di, Feng Jiang, Yang Liu, Xiansong Cheng
• Journal: Experimental and molecular pathology (Exp Mol Pathol) Vol. 115 Pg. 104475 (08 2020) ISSN: 1096-0945 [Electronic] Netherlands
• PMID: 32473154 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
• RNA, Small Interfering
• TFEB protein, rat

Topics

• Animals
• Autophagosomes (metabolism, ultrastructure)
• Basic Helix-Loop-Helix Leucine Zipper Transcription Factors (metabolism)
• Brain (pathology, ultrastructure)
• Brain Ischemia (pathology)
• Chronic Disease
• Down-Regulation
• Ischemic Postconditioning
• Lysosomes (metabolism, ultrastructure)
• Male
• Nerve Tissue (injuries, pathology)
• RNA, Small Interfering (metabolism)
• Rats, Wistar
• Up-Regulation