PKCε modulates NF-κB and AP-1 via mitogen-activated protein kinases in adult rabbit cardiomyocytes

Richard C X Li, Peipei Ping, Jun Zhang, William B. Wead, Xinan Cao, Jiuming Gao, Yuting Zheng, Shuang Huang, Jiahuai Han, Roberto Bolli

Research output: Contribution to journalArticle

Abstract

We have previously shown that protein kinase C (PKC) nuclear factor (NF)-κB, and mitogen-activated protein kinases (MAPKs) are essential signaling elements in ischemic preconditioning. In the present study, we examined whether activation of PKCε affects the activation ot NF-κB in cardiac myocytes and whether MAPKs are mediators of this signaling event. Activation of PKCε (+ 108% above control) in adult rabbit cardiomyocytes to a degree that has been previously shown to protect myocytes against hypoxic injury increased the DNA-binding activity of NF-κB (+164%) and activator protein (AP)-1 (+ 127%) but not that of Elk-1. Activation of PKCη did not have an effect on these transcription factors. Activation of PKCε also enhanced the phosphorylation activities of the p44/p42 MAPKs and the p54/p46 c-Jun NH2-terminal kinases (JNKs). PKCε-induced activation of NF-κB and AP-1 was completely abolished by inhibition of the p44/p42 MAPK pathway with PD98059 and by inhibition of the p54/p46 JNK pathway with a dominant negative mutant of MAPK kinase-4, indicating that both signaling pathways are necessary. Taken together, these data identify NF-κB and AP-1 as downstream targets of PKCε, thereby establishing a molecular link between activation of PKCε and activation of NF-κB and AP-1 in cardiomyocytes. The results further demonstrate that both the p44/p42 MAPK and the p54/p46 JNK signaling pathways are essential mediators of this event.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume279
Issue number4 48-4
StatePublished - 2000
Externally publishedYes

Fingerprint

Transcription Factor AP-1
Mitogen-Activated Protein Kinases
Cardiac Myocytes
Protein Kinase C
Rabbits
JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinase 1
MAP Kinase Kinase 4
Ischemic Preconditioning
Muscle Cells
DNA Damage
Transcription Factors
Phosphorylation

Keywords

  • Activator protein-1
  • Nuclear factor-κB
  • Protein kinase Cε

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

PKCε modulates NF-κB and AP-1 via mitogen-activated protein kinases in adult rabbit cardiomyocytes. / Li, Richard C X; Ping, Peipei; Zhang, Jun; Wead, William B.; Cao, Xinan; Gao, Jiuming; Zheng, Yuting; Huang, Shuang; Han, Jiahuai; Bolli, Roberto.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 279, No. 4 48-4, 2000.

Research output: Contribution to journalArticle

Li, RCX, Ping, P, Zhang, J, Wead, WB, Cao, X, Gao, J, Zheng, Y, Huang, S, Han, J & Bolli, R 2000, 'PKCε modulates NF-κB and AP-1 via mitogen-activated protein kinases in adult rabbit cardiomyocytes', American Journal of Physiology - Heart and Circulatory Physiology, vol. 279, no. 4 48-4.
Li, Richard C X ; Ping, Peipei ; Zhang, Jun ; Wead, William B. ; Cao, Xinan ; Gao, Jiuming ; Zheng, Yuting ; Huang, Shuang ; Han, Jiahuai ; Bolli, Roberto. / PKCε modulates NF-κB and AP-1 via mitogen-activated protein kinases in adult rabbit cardiomyocytes. In: American Journal of Physiology - Heart and Circulatory Physiology. 2000 ; Vol. 279, No. 4 48-4.
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T1 - PKCε modulates NF-κB and AP-1 via mitogen-activated protein kinases in adult rabbit cardiomyocytes

AU - Li, Richard C X

AU - Ping, Peipei

AU - Zhang, Jun

AU - Wead, William B.

AU - Cao, Xinan

AU - Gao, Jiuming

AU - Zheng, Yuting

AU - Huang, Shuang

AU - Han, Jiahuai

AU - Bolli, Roberto

PY - 2000

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N2 - We have previously shown that protein kinase C (PKC) nuclear factor (NF)-κB, and mitogen-activated protein kinases (MAPKs) are essential signaling elements in ischemic preconditioning. In the present study, we examined whether activation of PKCε affects the activation ot NF-κB in cardiac myocytes and whether MAPKs are mediators of this signaling event. Activation of PKCε (+ 108% above control) in adult rabbit cardiomyocytes to a degree that has been previously shown to protect myocytes against hypoxic injury increased the DNA-binding activity of NF-κB (+164%) and activator protein (AP)-1 (+ 127%) but not that of Elk-1. Activation of PKCη did not have an effect on these transcription factors. Activation of PKCε also enhanced the phosphorylation activities of the p44/p42 MAPKs and the p54/p46 c-Jun NH2-terminal kinases (JNKs). PKCε-induced activation of NF-κB and AP-1 was completely abolished by inhibition of the p44/p42 MAPK pathway with PD98059 and by inhibition of the p54/p46 JNK pathway with a dominant negative mutant of MAPK kinase-4, indicating that both signaling pathways are necessary. Taken together, these data identify NF-κB and AP-1 as downstream targets of PKCε, thereby establishing a molecular link between activation of PKCε and activation of NF-κB and AP-1 in cardiomyocytes. The results further demonstrate that both the p44/p42 MAPK and the p54/p46 JNK signaling pathways are essential mediators of this event.

AB - We have previously shown that protein kinase C (PKC) nuclear factor (NF)-κB, and mitogen-activated protein kinases (MAPKs) are essential signaling elements in ischemic preconditioning. In the present study, we examined whether activation of PKCε affects the activation ot NF-κB in cardiac myocytes and whether MAPKs are mediators of this signaling event. Activation of PKCε (+ 108% above control) in adult rabbit cardiomyocytes to a degree that has been previously shown to protect myocytes against hypoxic injury increased the DNA-binding activity of NF-κB (+164%) and activator protein (AP)-1 (+ 127%) but not that of Elk-1. Activation of PKCη did not have an effect on these transcription factors. Activation of PKCε also enhanced the phosphorylation activities of the p44/p42 MAPKs and the p54/p46 c-Jun NH2-terminal kinases (JNKs). PKCε-induced activation of NF-κB and AP-1 was completely abolished by inhibition of the p44/p42 MAPK pathway with PD98059 and by inhibition of the p54/p46 JNK pathway with a dominant negative mutant of MAPK kinase-4, indicating that both signaling pathways are necessary. Taken together, these data identify NF-κB and AP-1 as downstream targets of PKCε, thereby establishing a molecular link between activation of PKCε and activation of NF-κB and AP-1 in cardiomyocytes. The results further demonstrate that both the p44/p42 MAPK and the p54/p46 JNK signaling pathways are essential mediators of this event.

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