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Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Effects of microRNA‑338‑3p on morphine‑induced apoptosis and its underlying mechanisms
Hong-Liang Weng1, Ming-Jing Wang2
1Department of Anesthesia, Linyi Yishui Central Hospital, Linyi, Shandong 276400, P.R. China.
Abstract:
The aim of the present study was to investigate the effects of microRNA-338-3p (miR-338-3p) on morphine (MP)-induced apoptosis, and its underlying mechanisms. Freshly‑isolated mouse peritoneal macrophages were cultured in vitro and treated with MP following transfection with miR‑338‑3p mimic, inhibitor or controls. miR‑338‑3p expression levels increased significantly following MP treatment (P<0.01). This increase was enhanced following transfection with miR‑338‑3p mimic (P<0.05) and abrogated following transfection with miR‑338‑3p inhibitor (P<0.05). The apoptotic rate increased significantly in groups treated with MP (P<0.05); however, this increase was abrogated by transfection with miR‑338‑3p inhibitor (P<0.05). Bioinformatics software predicted that sex determining region Y‑box 4 (SOX4) was the target gene of miR‑338‑3p and this was verified using a dual‑luciferase reporter gene system. SOX4 mRNA and protein expression levels decreased significantly following MP treatment (P<0.05); however, this decrease was abrogated following transfection with miR‑338‑3p inhibitor (P<0.05). Caspase‑3 protein expression levels increased markedly following MP treatment (P<0.05); however, this increase was inhibited by transfection with miR‑338‑3p inhibitor (P<0.05). Therefore, decreased expression of miR‑338‑3p may suppress MP‑induced apoptosis, potentially via the upregulation of SOX4 expression and the caspase‑3‑dependent apoptotic signaling pathway.
Insights
MicroRNA-338-3p (miR-338-3p) plays a role in morphine-induced apoptosis. Decreased miR-338-3p may suppress this apoptosis by upregulating SOX4 and affecting the caspase-3 pathway.
Area of Science:
- Molecular Biology
- Cell Biology
- Pharmacology
Background:
- Opioid analgesics like morphine can induce apoptosis in cells.
- MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and are implicated in various cellular processes, including apoptosis.
- Understanding the role of specific miRNAs in drug-induced apoptosis is crucial for developing safer therapeutic strategies.
Purpose of the Study:
- To investigate the effect of microRNA-338-3p (miR-338-3p) on morphine (MP)-induced apoptosis in mouse peritoneal macrophages.
- To elucidate the underlying molecular mechanisms involved in this process.
Main Methods:
- Primary mouse peritoneal macrophages were cultured in vitro.
- Cells were treated with morphine (MP) and transfected with miR-338-3p mimic, inhibitor, or control sequences.
- miR-338-3p expression, apoptosis rates, SOX4 mRNA and protein levels, and Caspase-3 protein levels were analyzed.
Main Results:
- MP treatment significantly increased miR-338-3p expression and induced apoptosis.
- Inhibition of miR-338-3p abrogated MP-induced apoptosis and SOX4 downregulation.
- MP treatment decreased SOX4 expression, while Caspase-3 levels increased, effects reversed by miR-338-3p inhibition.
Conclusions:
- Decreased miR-338-3p expression may promote MP-induced apoptosis.
- The mechanism involves the upregulation of SOX4 and activation of the caspase-3-dependent apoptotic pathway.
- miR-338-3p acts as a regulator in morphine-induced cellular apoptosis.
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