Nuclear-envelope nucleoside triphosphatase kinetics and mRNA transport 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 activity and poly(A)+ mRNA transport were studied in nuclear envelope vesicles (NEVs) prepared from canine parietal cortex isolated after 20 minutes of ischemia or 20 minutes of ischemia and 2 or 6 hours of reperfusion.

RESULTS

Brain NEV NTPase Michaelis-Menten constant (Km) and maximum uptake velocity (Vmax) and the ATP-stimulated poly(A)+ mRNA egress rates were not significantly affected by ischemia and reperfusion. In vitro exposure of the NEVs to the OH. radical-generating system completely abolished NTPase activity.

CONCLUSION

We conclude that brain ischemia and reperfusion do not induce direct inhibition of nucleocytoplasmic transport of poly(A)+ mRNA. This suggests that the nuclear membrane is not exposed to significant concentrations of OH. radical during reperfusion.