Abstract
Anesthetic preconditioning (APC), defined as brief exposure to inhalational anesthetics before cardiac ischemia-reperfusion (I/R), limits injury in both animal models and in humans. APC can result in the production of reactive oxygen species (ROS), and prior work has shown that APC can modify activation of NF-κB during I/R, with consequent reduction in the expression of inflammatory mediators. However, the role of NF-κB activation before I/R is unknown. Therefore, these experiments tested the hypothesis that APC-induced ROS results in activation of NF-κB before I/R, with consequent increased expression of antiapoptotic proteins such as Bcl-2 and decreased apoptosis. Experiments utilized an established perfused heart rat model of sevoflurane APC and I/R. The role of NF-κB was defined by a novel method of transient inhibition of the regulatory kinase IKK using the reversible inhibitor SC-514. In addition to functional measures of left ventricular developed and end-diastolic pressure, phosphorylation of IκBα and activation of NF-κB were measured along with cytosolic protein content of Bcl-2, release of cytochrome c, and degradation of caspase-3. APC resulted in ROS-dependent phosphorylation of IκBα and activation of NF-κB before I/R. APC also increased the expression of Bcl-2 before I/R. In addition to functional protection following I/R, APC resulted in lower release of cytochrome c and caspase-3 degradation. These protective effects of APC were abolished by transient inhibition of IκBα phosphorylation and NF-κB activation by SC-514 followed by washout. ROS-dependent activation of NF-κB by APC before I/R is a critical element in the protective effect of APC. APC reduces apoptosis and functional impairment by increasing Bcl-2 expression before I/R. Interventions that increase NF-κB activation before I/R should protect hearts from I/R injury.
| Original language | English (US) |
|---|---|
| Journal | American Journal of Physiology - Heart and Circulatory Physiology |
| Volume | 296 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 2009 |
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Keywords
- Nuclear factor-κB
- Reactive oxygen species
ASJC Scopus subject areas
- Physiology
- Physiology (medical)
- Cardiology and Cardiovascular Medicine
Cite this
Activation of NF-κB is a critical element in the antiapoptotic effect of anesthetic preconditioning. / Lu, Xiyuan; Liu, Hong; Wang, Lianguo; Schaefer, Saul.
In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 296, No. 5, 05.2009.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Activation of NF-κB is a critical element in the antiapoptotic effect of anesthetic preconditioning
AU - Lu, Xiyuan
AU - Liu, Hong
AU - Wang, Lianguo
AU - Schaefer, Saul
PY - 2009/5
Y1 - 2009/5
N2 - Anesthetic preconditioning (APC), defined as brief exposure to inhalational anesthetics before cardiac ischemia-reperfusion (I/R), limits injury in both animal models and in humans. APC can result in the production of reactive oxygen species (ROS), and prior work has shown that APC can modify activation of NF-κB during I/R, with consequent reduction in the expression of inflammatory mediators. However, the role of NF-κB activation before I/R is unknown. Therefore, these experiments tested the hypothesis that APC-induced ROS results in activation of NF-κB before I/R, with consequent increased expression of antiapoptotic proteins such as Bcl-2 and decreased apoptosis. Experiments utilized an established perfused heart rat model of sevoflurane APC and I/R. The role of NF-κB was defined by a novel method of transient inhibition of the regulatory kinase IKK using the reversible inhibitor SC-514. In addition to functional measures of left ventricular developed and end-diastolic pressure, phosphorylation of IκBα and activation of NF-κB were measured along with cytosolic protein content of Bcl-2, release of cytochrome c, and degradation of caspase-3. APC resulted in ROS-dependent phosphorylation of IκBα and activation of NF-κB before I/R. APC also increased the expression of Bcl-2 before I/R. In addition to functional protection following I/R, APC resulted in lower release of cytochrome c and caspase-3 degradation. These protective effects of APC were abolished by transient inhibition of IκBα phosphorylation and NF-κB activation by SC-514 followed by washout. ROS-dependent activation of NF-κB by APC before I/R is a critical element in the protective effect of APC. APC reduces apoptosis and functional impairment by increasing Bcl-2 expression before I/R. Interventions that increase NF-κB activation before I/R should protect hearts from I/R injury.
AB - Anesthetic preconditioning (APC), defined as brief exposure to inhalational anesthetics before cardiac ischemia-reperfusion (I/R), limits injury in both animal models and in humans. APC can result in the production of reactive oxygen species (ROS), and prior work has shown that APC can modify activation of NF-κB during I/R, with consequent reduction in the expression of inflammatory mediators. However, the role of NF-κB activation before I/R is unknown. Therefore, these experiments tested the hypothesis that APC-induced ROS results in activation of NF-κB before I/R, with consequent increased expression of antiapoptotic proteins such as Bcl-2 and decreased apoptosis. Experiments utilized an established perfused heart rat model of sevoflurane APC and I/R. The role of NF-κB was defined by a novel method of transient inhibition of the regulatory kinase IKK using the reversible inhibitor SC-514. In addition to functional measures of left ventricular developed and end-diastolic pressure, phosphorylation of IκBα and activation of NF-κB were measured along with cytosolic protein content of Bcl-2, release of cytochrome c, and degradation of caspase-3. APC resulted in ROS-dependent phosphorylation of IκBα and activation of NF-κB before I/R. APC also increased the expression of Bcl-2 before I/R. In addition to functional protection following I/R, APC resulted in lower release of cytochrome c and caspase-3 degradation. These protective effects of APC were abolished by transient inhibition of IκBα phosphorylation and NF-κB activation by SC-514 followed by washout. ROS-dependent activation of NF-κB by APC before I/R is a critical element in the protective effect of APC. APC reduces apoptosis and functional impairment by increasing Bcl-2 expression before I/R. Interventions that increase NF-κB activation before I/R should protect hearts from I/R injury.
KW - Nuclear factor-κB
KW - Reactive oxygen species
UR - http://www.scopus.com/inward/record.url?scp=66149094966&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=66149094966&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.01282.2008
DO - 10.1152/ajpheart.01282.2008
M3 - Article
C2 - 19304943
AN - SCOPUS:66149094966
VL - 296
JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
SN - 1931-857X
IS - 5
ER -