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SNHG5 Upregulated by Dexmedetomidine Alleviates Myocardial Ischemia/Reperfusion Injury Through LIN28A-Mediated BCAT1
Jingjia Yu1, Fei Ye1, Wenzhi Luo1
1Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China.
Abstract:
SNHG5 serves as a key factor in regulating various cancers, and Dexmedetomidine (Dex) protects against myocardial ischemia/reperfusion (I/R) injury. However, the role of SNHG5 in Dex-mediated protection during myocardial I/R remains uninvestigated. In this study, models of rat myocardial I/R injury and hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury were generated. The infarct size, histological changes and apoptosis in heart tissues were evaluated by TTC, HE, and TUNEL staining. CCK-8, flow cytometry and immunofluorescence were employed to assess cell viability, apoptosis and autophagosome-lysosome fusion in H9c2 cells. The associations among SNHG5, LIN28A and BCAT1 mRNA were detected by RNA pull-down, RIP, and RNA fluorescence in situ hybridization (FISH) assays. Western Blot, qRT-PCR and immunohistochemistry were employed to detect the expression of key molecules. Our results revealed that Dex ameliorated myocardial I/R injury and H/R-induced impairments in H9c2 cells by enhancing autophagy. Moreover, Dex led to a rebound of SNHG5 in the heart tissues of I/R rats and H/R-treated H9c2 cells, and functional studies revealed that Dex protected against cardiac impairments through SNHG5-dependent autophagy in vitro and in vivo. Furthermore, SNHG5 alleviated H/R-induced impairments by recruiting LIN28A protein, which was subsequently bound to BCAT1 mRNA and maintained its stability. In conclusion, our findings demonstrated that SNHG5, when upregulated by Dex, alleviated myocardial I/R injury through LIN28A-mediated BCAT1 mRNA stabilization and autophagy enhancement.
Insights
Dexmedetomidine (Dex) protects heart cells from injury by increasing SNHG5, which enhances autophagy. This mechanism involves SNHG5 recruiting LIN28A to stabilize BCAT1 mRNA, ultimately reducing cardiac damage.
Area of Science:
- Cardiovascular Biology
- Molecular Oncology
- Cellular Physiology
Background:
- Dexmedetomidine (Dex) is known to protect against myocardial ischemia/reperfusion (I/R) injury.
- Small nucleolar RNA host gene 5 (SNHG5) is implicated in various cancers, but its role in Dex-mediated cardioprotection is unexplored.
Purpose of the Study:
- To investigate the role of SNHG5 in Dexmedetomidine's protective effects against myocardial I/R injury.
- To elucidate the molecular mechanisms underlying SNHG5-mediated cardioprotection.
Main Methods:
- Established rat myocardial I/R and H9c2 cell hypoxia/reoxygenation (H/R) injury models.
- Assessed cardiac function and apoptosis using TTC, HE, TUNEL staining, CCK-8, and flow cytometry.
- Investigated molecular interactions using RNA pull-down, RIP, FISH, Western Blot, qRT-PCR, and immunohistochemistry.
Main Results:
- Dexmedetomidine ameliorated myocardial I/R and H/R-induced cell injury by enhancing autophagy.
- Dexmedetomidine upregulated SNHG5 in cardiac tissues and cells, and SNHG5 mediated the protective effects of Dex.
- SNHG5 protected against H/R injury by recruiting LIN28A, which stabilized BCAT1 mRNA, thereby promoting autophagy.
Conclusions:
- Dexmedetomidine protects against myocardial I/R injury by upregulating SNHG5, which enhances autophagy via the LIN28A/BCAT1 pathway.
- SNHG5 plays a crucial role in mediating the cardioprotective effects of Dexmedetomidine.
- Targeting the SNHG5/LIN28A/BCAT1 axis represents a potential therapeutic strategy for myocardial I/R injury.
