Coniferaldehyde inhibits LPS-induced apoptosis through the PKC α/β II/Nrf-2/HO-1 dependent pathway in RAW264.7 macrophage cells

  • Environ Toxicol Pharmacol. 2016 Dec;48:85-93. doi: 10.1016/j.etap.2016.10.016.
Ki Mo Kim  1 ,  Deok Rim Heo  1 ,  Young-A Kim  1 ,  Jun Lee  1 ,  No Soo Kim  1 ,  Ok-Sun Bang  2
Affiliations
  • 1. KM Convergence Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon, 305-811, Republic of Korea.
  • 2. KM Convergence Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon, 305-811, Republic of Korea. Electronic address: [email protected].
PMID: 27770660 DOI: 10.1016/j.etap.2016.10.016
Abstract

Coniferaldehyde (CA) exerts anti-inflammatory properties by inducing heme oxygenase-1 (HO-1). To define the regulation mechanism by which CA induces a cytoprotective function and HO-1 expression, the up-stream regulations involved in the activation of nuclear transcription factor-erythroid 2-related factor (Nrf)-2/HO-1 pathway were investigated. CA dramatically increased the Nrf-2 nuclear translocation and HO-1 expression. Lipopolysaccharide (LPS)-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, and cell death were down-regulated by CA, which were reversed by inhibition of HO-1 activity. Furthermore, CA specifically enhanced the phosphorylation of protein kinase C (PKC) α/β II. Selective inhibition of PKC α/β II using Go6976 or siRNA abolished the CA-induced Nrf-2/HO-1 signaling, and consequently suppressed the cytoprotective activity of CA on the LPS-induced cell death. Together, our results elucidate the regulatory mechanism of PKC α/β II as the upstream molecule of Nrf-2 required for HO-1 expression during CA-induced anti-inflammatory cytoprotective function in LPS stimulated macrophages.

Keywords
Apoptosis; Coniferaldehyde; HO-1; Macrophages; Nrf-2; PKC α/β II.
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