RESUMO
PURPOSE: Adenosine monophosphate-activated protein kinase (AMPK) is thought to inhibit cell proliferation or promote cell death, but the details remain unclear. In this study, we propose that AMPK inhibits the expression of anti-apoptotic B-cell lymphoma 2 (Bcl-2) by relying on the hypoxia-inducible factor 1 alpha (HIF-1α)-induced caveolin-1 (Cav-1) expression pathway in noninvasive human bladder tumor (RT4) cells. METHODS: In cells exposed to a hypoxic environment (0.5% oxygen), the levels of expression and phospho-activity of the relevant signaling enzymes were examined via Western blots and reverse transcription-polymerase chain reaction. Cell proliferation was assessed using a Cell Counting Kit-8 assay. RESULTS: The level of expression of Cav-1 was very low or undetectable in RT4 cells. Hypoxia was associated with significantly decreased cell growth, along with marked induction of HIF-1α and Cav-1 expression; additionally, it suppressed the expression of the antiapoptotic marker Bcl-2 while leaving AMPK activity unchanged. Under hypoxic conditions, HIF-1α acts as a transcription factor for Cav-1 mRNA gene expression. The cell growth and Bcl-2 expression suppressed under hypoxia were reversed along with decreases in the induced HIF-1α and Cav-1 levels by AMPK activation with metformin (1mM) or phenformin (0.1mM). In addition, pretreatment with AMPK small interfering RNA not only increased the hypoxia-induced expression of HIF-1α and Cav-1, but also reversed the suppression of Bcl-2 expression. These results suggest that HIF-1α and Cav-1 expression in hypoxic environments is regulated by basal AMPK activity; therefore, the inhibition of Bcl-2 expression cannot be expected when AMPK activity is suppressed, even if Cav-1 expression is elevated. CONCLUSION: For the first time, we find that AMPK activation can regulate HIF-1α induction as well as HIF-1α-induced Cav1 expression, and the hypoxia-induced inhibitory effect on the antiapoptotic pathway in RT4 cells is due to Cav-1-dependent AMPK activity.
RESUMO
BACKGROUND: Laryngoscopic intubation and supraglottic airway device insertion can prolong the corrected QT (QTc) interval during anaesthetic induction even in healthy patients. No prior study has compared the effect of laryngoscopic intubation and supraglottic airway device, i-gel, insertion on the QTc interval change. METHODS: Patients were randomised to either the intubation group (N.=25) or the i-gel group (N.=25) before induction. The QT interval was sequentially measured in lead II following a standard anaesthetic technique for induction using propofol and sevoflurane. Four sequential QT values were applied to the Bazett's formula to correct for the effect of heart rate on the QT interval, and then averaged. The peak QTc interval, the duration of QTc prolongation >20 ms compared to the QTc value immediately before intubation or i-gel insertion and the incidence of the QTc intervals >500 ms were measured. RESULTS: The peak QTc interval was lower in i-gel group (458.4±24.3 ms) than in intubation group (488.6±32.6 ms) (P=0.001). The duration of QTc prolongation >20 ms compared to the QTc values at immediately before intubation or i-gel insertion was significantly longer in the intubation group (136.5±104.5 s) than that of the i-gel group (56.9±56.5 s) (P=0.031). The number of patients with QTc interval >500 ms was significantly lower in the i-gel group (4%) than in the intubation group (48%). CONCLUSIONS: The insertion of the i-gel produces less QTc interval change than laryngoscopic intubation. The i-gel may be advantageous to patients who are at risk of QTc prolongation, high blood pressure and tachycardia.