Cardioprotection involves activation of NF-κB via PKC-dependent tyrosine and serine phosphorylation of IκB-α

Jun Zhang, Peipei Ping, Thomas M. Vondriska, Xian Liang Tang, Guang Wu Wang, Ernest M. Cardwell, Roberto Bolli

Research output: Contribution to journalArticle

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 languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume285
Issue number4 54-4
StatePublished - Oct 1 2003
Externally publishedYes

Fingerprint

Ischemic Preconditioning
Serine
Tyrosine
Phosphorylation
Protein-Tyrosine Kinases
src-Family Kinases
Coronary Occlusion
Reperfusion
Phosphotransferases
Rabbits
Proteins

Keywords

  • Ischemic preconditioning
  • Posttranslational modification
  • Protein kinase C
  • Signaling module
  • Src tyrosine kinase

ASJC Scopus subject areas

  • Physiology

Cite this

Zhang, J., Ping, P., Vondriska, T. M., Tang, X. L., Wang, G. W., Cardwell, E. M., & Bolli, R. (2003). Cardioprotection involves activation of NF-κB via PKC-dependent tyrosine and serine phosphorylation of IκB-α. American Journal of Physiology - Heart and Circulatory Physiology, 285(4 54-4).

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 journalArticle

Zhang, Jun ; Ping, Peipei ; Vondriska, Thomas M. ; Tang, Xian Liang ; Wang, Guang Wu ; Cardwell, Ernest M. ; Bolli, Roberto. / Cardioprotection involves activation of NF-κB via PKC-dependent tyrosine and serine phosphorylation of IκB-α. In: American Journal of Physiology - Heart and Circulatory Physiology. 2003 ; Vol. 285, No. 4 54-4.
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