Inhibition of autophagy by esketamine attenuates hypoxia/reoxygenation injury in cardiomyocytes via inhibition of Ca2+/CaMKKβ/AMPK/mTOR pathway by down-regulation of transient receptor potential vanilloid 1 expression.
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society – April 01, 2025
Source: PubMed
Summary
Heart cells under stress can repair themselves through a process called autophagy, but sometimes this self-repair goes wrong. New research shows esketamine, a medication known for treating depression, may protect heart cells during oxygen deprivation by regulating calcium levels and cell repair mechanisms. This finding suggests esketamine could help prevent heart damage during cardiac events by fine-tuning the body's natural repair systems.
Abstract
This research sought to determine the influence of esketamine (ESK) on hypoxia/reoxygenation (H/R) injury in cardiomyocytes by blocking autophagy via the transient receptor potential vanilloid type 1 (TRPV1)/ Ca2+/ calmodulin-dependent protein kinase β (CaMKKβ)/ adenosine monophosphate (AMP)-activated protein kinase (AMPK)/ mammalian target of rapamycin (mTOR) pathway. H9c2 cardiomyocytes were hypoxic for 4 h and reoxygenated for 6 h. H9c2 cells were pretreated with ESK (30 μg/ml) before hypoxia. H9c2 cells were transfected with plasmid vectors that interfered with TRPV1 or CaMKKβ, and the success of the transfections was verified by RT-qPCR. Cell viability was detected by MTT assay; apoptosis was detected by flow cytometry; intracellular Ca2+ concentration ([Ca2+]i) was assessed using fluorescent dye Fluo-3 AM/Pluronic F127, and LC3-I, LC3-II, Beclin-1, and CaMKKβ/AMPK/mTOR-related proteins were detected by Western blot. In results: ESK treatment inhibited H/R-induced cell injury, cellular autophagy, and [Ca2+]i elevation. Induction of autophagy or [Ca2+]i elevation attenuated the ameliorative effect of ESK on H/R-induced cell injury. Upregulating TRPV1 attenuated We conclude that ESK-induced protection against H/R injury, as well as reduced the effect on the CaMKKβ/AMPK/mTOR pathway. ESK attenuates H/R cardiomyocyte injury by hindering autophagy through the TRPV1/Ca2+/CaMKKβ/AMPK/mTOR pathway.