Abstract
Previous studies indicated that activation of PKC and Src tyrosine kinases by ischemic preconditioning (PC) may participate in the activation of NF-κB. However, the molecular mechanisms underlying activation of NF-κB during ischemic PC remain unknown. In the hearts of conscious rabbits, it was found that ischemic PC (6 cycles of 4-min coronary occlusion and 4-min reperfusion) significantly induced both tyrosine (+226.9 ± 42%) and serine (+137.0 ± 36%) phosphorylation of the NF-κB inhibitory protein IκB-α, concomitant with increased activation of the IKB-α kinases IKKα (+255.0 ± 46%) and IKKβ (+173.1 ± 35%). Furthermore, both tyrosine and serine phosphorylation of IκB-α were blocked by pretreatment with either the nonreceptor tyrosine kinase inhibitor lavendustin-A (LD-A) or the PKC inhibitor chelerythrine (Che) (both given at doses previously shown to block ischemic PC). Interestingly, Che completely abolished PC-induced activation of IKKα/β, whereas LD-A had no effect. In addition, IκB-α protein level did not change during ischemic PC. Together, these data indicate that ischemic PC-induced activation of NF-κB occurs through both tyrosine and serine phosphorylation of IκB-α and is regulated by nonreceptor tyrosine kinases and PKC.
| Original language | English (US) |
|---|---|
| Journal | American Journal of Physiology - Heart and Circulatory Physiology |
| Volume | 285 |
| Issue number | 4 54-4 |
| State | Published - Oct 1 2003 |
| Externally published | Yes |
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Keywords
- Ischemic preconditioning
- Posttranslational modification
- Protein kinase C
- Signaling module
- Src tyrosine kinase
ASJC Scopus subject areas
- Physiology
Cite this
Cardioprotection involves activation of NF-κB via PKC-dependent tyrosine and serine phosphorylation of IκB-α. / Zhang, Jun; Ping, Peipei; Vondriska, Thomas M.; Tang, Xian Liang; Wang, Guang Wu; Cardwell, Ernest M.; Bolli, Roberto.
In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 285, No. 4 54-4, 01.10.2003.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cardioprotection involves activation of NF-κB via PKC-dependent tyrosine and serine phosphorylation of IκB-α
AU - Zhang, Jun
AU - Ping, Peipei
AU - Vondriska, Thomas M.
AU - Tang, Xian Liang
AU - Wang, Guang Wu
AU - Cardwell, Ernest M.
AU - Bolli, Roberto
PY - 2003/10/1
Y1 - 2003/10/1
N2 - Previous studies indicated that activation of PKC and Src tyrosine kinases by ischemic preconditioning (PC) may participate in the activation of NF-κB. However, the molecular mechanisms underlying activation of NF-κB during ischemic PC remain unknown. In the hearts of conscious rabbits, it was found that ischemic PC (6 cycles of 4-min coronary occlusion and 4-min reperfusion) significantly induced both tyrosine (+226.9 ± 42%) and serine (+137.0 ± 36%) phosphorylation of the NF-κB inhibitory protein IκB-α, concomitant with increased activation of the IKB-α kinases IKKα (+255.0 ± 46%) and IKKβ (+173.1 ± 35%). Furthermore, both tyrosine and serine phosphorylation of IκB-α were blocked by pretreatment with either the nonreceptor tyrosine kinase inhibitor lavendustin-A (LD-A) or the PKC inhibitor chelerythrine (Che) (both given at doses previously shown to block ischemic PC). Interestingly, Che completely abolished PC-induced activation of IKKα/β, whereas LD-A had no effect. In addition, IκB-α protein level did not change during ischemic PC. Together, these data indicate that ischemic PC-induced activation of NF-κB occurs through both tyrosine and serine phosphorylation of IκB-α and is regulated by nonreceptor tyrosine kinases and PKC.
AB - Previous studies indicated that activation of PKC and Src tyrosine kinases by ischemic preconditioning (PC) may participate in the activation of NF-κB. However, the molecular mechanisms underlying activation of NF-κB during ischemic PC remain unknown. In the hearts of conscious rabbits, it was found that ischemic PC (6 cycles of 4-min coronary occlusion and 4-min reperfusion) significantly induced both tyrosine (+226.9 ± 42%) and serine (+137.0 ± 36%) phosphorylation of the NF-κB inhibitory protein IκB-α, concomitant with increased activation of the IKB-α kinases IKKα (+255.0 ± 46%) and IKKβ (+173.1 ± 35%). Furthermore, both tyrosine and serine phosphorylation of IκB-α were blocked by pretreatment with either the nonreceptor tyrosine kinase inhibitor lavendustin-A (LD-A) or the PKC inhibitor chelerythrine (Che) (both given at doses previously shown to block ischemic PC). Interestingly, Che completely abolished PC-induced activation of IKKα/β, whereas LD-A had no effect. In addition, IκB-α protein level did not change during ischemic PC. Together, these data indicate that ischemic PC-induced activation of NF-κB occurs through both tyrosine and serine phosphorylation of IκB-α and is regulated by nonreceptor tyrosine kinases and PKC.
KW - Ischemic preconditioning
KW - Posttranslational modification
KW - Protein kinase C
KW - Signaling module
KW - Src tyrosine kinase
UR - http://www.scopus.com/inward/record.url?scp=0141565333&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0141565333&partnerID=8YFLogxK
M3 - Article
C2 - 12829431
AN - SCOPUS:0141565333
VL - 285
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6135
IS - 4 54-4
ER -