Investigation of the molecular mechanisms of propofol toxiciy by using mitochondria cybrids

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K15682
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Anesthesiology
• Research Institution: Kansai Medical University
• Principal Investigator: HIROTA Kiichi 関西医科大学, 医学部, 教授 (00283606)
• Co-Investigator(Kenkyū-buntansha): 竹永 啓三 島根大学, 医学部, 准教授 (80260256)
• Co-Investigator(Renkei-kenkyūsha): MATSUO Yoshiyuki 関西医科大学, 医学部, 講師 (50447926)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: プロポフォール / ミトコンドリア / サイブリッド / 細胞死

Outline of Final Research Achievements

The intravenous anesthetic propofol has been used for the induction and maintenance of anesthesia and sedation in critical patient care. However, the rare but severe complication propofol infusion syndrome (PRIS) can occur. In vivo and in vitro evidence suggests that the propofol toxicity is related to the impaired mitochondrial function. Therefore we investigated effects of propofol on cell metabolism and death using a series of established cell lines of various origins, including trans-mitochondrial cybrids, with defined mitochondrial DNA deficits. We demonstrated that supraclinical concentrations of propofol in not less than 50 μM disturbed the mitochondrial function and induced a metabolic switch, from oxidative phosphorylation to glycolysis, by targeting mitochondrial complexes I, II and III. This disturbance in mitochondrial electron transport caused the generation of reactive oxygen species, resulting in apoptosis.

Free Research Field

麻酔科学