HEAT SHOCK PROTEIN 70 INHIBITS NF-κB ACTIVITY AND IκB DEGRADATION IN INFECTIOUS CEREBRAL INJURY IN
RAT
Mao D-A1, Yang
Y-J2, Yu Y2, Yu P-L2
1 The Second Hospital of Xiang-Ya School of Medicine,
Central South University, Changsha, China
2 The Hospital of Xiang-Ya School of Medicine, Central
South University, China
Objective: To
explore heat shock protein 70 (HSP70) inhibits nuclear factor-kappa B (NF-κ B ) activity and
inhibitory-kappa B (IκB)
degradation in infectious cerebral injury in rat.
Methods: Adult
Sprague-Dawley rats were randomly divided into three groups: injection of
Pertussis Bacilli suspension via the left internal carotid artery (PB). PB
plus heat shock response pretreatment (HSR), the anesthetized rats were
placed in a prewarmed water incubator (45℃)
until their rectal temperature was raised to 42℃, maintained for 15 min in 42℃, and then put in room temperature for 24 hours
before injecting PB into the left internal carotid artery. Injection of
normal saline instead of PB as normal control (NS). The rats were killed at
2,4,8,24 hours after injection of PB or NS, respectively. Water Content
(WC), sodium (Na+) and potassium (K+) concentrations
in the brain tissue were measured. The expressions of HSP70 and IκB was evaluated by Western
blot and NF-KB complexes activity was detected by electrophoretic mobility
shift assay (EMSA) in nuclear extracts of neurocytes.
Results: WC and Na+
were significantly lower in HSR than in PB (P<0.01), While K+
was higher in HSR than in PB (P<0.01) except at 24 hour. HSP 70 was
over-expressed after HSR. NF-κB
was activated at 2,4,8 hour with a peak activity seen at 24 hour in PB. IκB-a expression began to
decrease in 2 hour and reached to the lowest level in 24 hour in PB. The
increase of NF-κB was markedly attenuated
with HSR pretreatment and the expression of IκB was higher in HSR.
Conclusions: The
results suggest that HSP 70 have protective effects against PB-induced
cerebral injury and the protection to be related with inhibiting effects on
degradation of IκB-a and
activation of NF-κB.