Abstract
BackgroundWe 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.MethodsPrimary 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.ResultsPropofol 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.ConclusionPropofol exposure decreased tPA release in developing hippocampal neurons. The addition of tPA could partially reverse the apoptotic effect of propofol.
Highlights
We investigated the effect of propofol on the tissue plasminogen activator release in developing hippocampal neurons, and explored the effects of exogenous tPA on the propofol-induced neuron apoptosis
We examined whether propofol decreases tPA release, which leads to decrease proBDNF, in hippocampal neurons
The data from the present study indicated that propofol could induce apoptosis in cultured developing hippocampal neurons, which are consistent with the findings from the previous studies (Yu et al 2013; Pearn et al 2012; Liu et al 2014; Twaroski et al 2014)
Summary
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. The brain-derived neurotrophic factor (BDNF) is stored as a proneurotrophin (proBDNF) within synaptic vesicles and is proteolytically cleaved to mature BDNF (mBDNF) in the synaptic cleft by plasmin (Lee et al 2001; Keifer et al 2009; Lu et al 2006). The mBDNF bind with the receptor kinase B and leads to neurite outgrowth and synapse stabilization and maturation (Lee et al 2001; Keifer et al 2009; Lu et al 2005).While the proBDNF binds to the p75 neurotrophin receptor (p75NTR) and initiates cellular processes that inhibit axonal elongation and cause growth cone collapse and apoptosis (Huettner and Baughman 1986). When the tPA is decreased, the convertion of plasminogen into plasmin may be blunted, and the number of proBDNF is increased, which leads to inhibition of axonal elongation, growth cone collapse, and apoptosis
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