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Tissue plasminogen activator (tPA) attenuates propofol-induced apoptosis in developing hippocampal neurons
Chao Liang1, Ming Ding1, Fang Du1
1Department of Anesthesiology, Zhongshan Hospital, Fudan University, Fenglin Road 180, Shanghai, 200032 China.
Background:
We investigated the effect of propofol on the tissue plasminogen activator (tPA) release in developing hippocampal neurons, and explored the effects of exogenous tPA on the propofol-induced neuron apoptosis.
Methods:
Primary hippocampal neurons isolated from neonatal Sprague-Dawley rats were exposed to propofol (20, 50, and 100 μM) for 6 h either one time or three times. Finally, neurons were pretreated with exogenous tPA (5 µg/ml), followed by propofol exposure (100 μM, 6 h). The neuron apoptosis was detected by terminal transferase deoxyuridine triphosphate-biotin nick-end labeling (TUNEL) and the protein expression of cleaved caspase-3 (Cl-Csp3) was analyzed by western blot, the tPA in media was tested by enzyme-linked immunosorbent assay.
Results:
Propofol exposure significantly increased the number of TUNEL-positive neurons and Cl-Csp3 expression in developing hippocampal neurons. Propofol decreased tPA level in the media of developing hippocampal neurons. The neuron appotosis induced by propofol was attenuated by pretreatment of tPA.
Conclusion:
Propofol exposure decreased tPA release in developing hippocampal neurons. The addition of tPA could partially reverse the apoptotic effect of propofol.
