Identification of Candidate Genes and Pathways in Dexmedetomidine-Induced Cardioprotection in the Rat Heart by Bioinformatics Analysis.

Abstract

Dexmedetomidine (DEX), a highly selective alpha2 adrenergic receptor agonist, directly protects hearts against ischemia/reperfusion (I/R) injury. However, the detailed mechanism has not been fully elucidated. We studied differentially expressed mRNAs and miRNAs after DEX administration in rat hearts by comprehensive analysis. Additionally, bioinformatics analysis was applied to explore candidate genes and pathways that might play important roles in DEX-induced cardioprotection. The results of microarray analysis showed that 165 mRNAs and 6 miRNAs were differentially expressed after DEX administration. Through bioinformatics analysis using differentially expressed mRNAs, gene ontology (GO) terms including MAP kinase tyrosine/serine/threonine phosphatase activity and pathways including the p53 pathway were significantly enriched in the down-regulated mRNAs. Dusp1 and Atm were associated with the GO term of MAP kinase tyrosine/serine/threonine phosphatase activity and the p53 pathway, respectively. On the other hand, no significant pathway was found in the target mRNAs of deregulated miRNAs. The results indicated some possible key genes and pathways that seem to be of significance in DEX-induced cardioprotection, although miRNAs seem to be unlikely to contribute to cardioprotection induced by DEX.

• Authors: Yusuke Yoshikawa, Naoyuki Hirata, Hirofumi Terada, Yasuaki Sawashita, Michiaki Yamakage
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 20 Issue 7 (Apr 01 2019) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 30939728 (Publication Type: Journal Article)

Chemical References

• Cardiotonic Agents
• Tumor Suppressor Protein p53
• Dexmedetomidine
• Ataxia Telangiectasia Mutated Proteins
• Dual Specificity Phosphatase 1
• Dusp1 protein, rat

Topics

• Animals
• Ataxia Telangiectasia Mutated Proteins (genetics, metabolism)
• Cardiotonic Agents (pharmacology, therapeutic use)
• Dexmedetomidine (pharmacology, therapeutic use)
• Dual Specificity Phosphatase 1 (genetics, metabolism)
• Gene Expression Profiling
• Heart (drug effects)
• MAP Kinase Signaling System
• Male
• Myocardial Reperfusion Injury (drug therapy, genetics, metabolism)
• Rats
• Rats, Wistar
• Transcriptome
• Tumor Suppressor Protein p53 (genetics, metabolism)