NUCLEAR-ENVELOPE NUCLEOSIDE TRIPHOSPHATASE KINETICS AND MESSENGER-RNATRANSPORT FOLLOWING BRAIN ISCHEMIA AND REPERFUSION

Study Hypothesis: We attempted to determine whether the reduced egress of mRNA from brain nuclei following in vivo ischemia and reperfusion is caused by direct damage to the nuclear pore-associated NTPase that impairs the system for nuclear export of polyadenylated, or poly (A)(), mRNA. Design: Prospective animal study. Interventions: NTPase activ ity and poly(A)(+) mRNA transport were studied in nuclear envelope ves icles (NEVs) prepared from canine parietal cortex isolated after 20 mi nutes of ischemia or 20 minutes of ischemia and 2 or 6 hours of reperf usion. Results: Brain NEV NTPase Michaelis-Menten constant (K-m) and m aximum uptake velocity (V-max) and the ATP-stimulated poly(A)(+) mRNA egress rates were not significantly affected by ischemia and reperfusi on. In vitro exposure of the NEVs to the OH . radical-generating syste m completely abolished NTPase activity.Conclusion: We conclude that br ain ischemia and reperfusion do not induce direct inhibition of nucleo cytoplasmic transport of poly(A)(+) mRNA. This suggests that the nucle ar membrane is not exposed to significant concentrations of OH . radic al during reperfusion.