Acrolein Induces Heme Oxygenase-1 through PKC-δ and PI3K in Human Bronchial Epithelial Cells

• DOI: 10.1165/rcmb.2007-0260oc
• Publication Date: 2007-11-30T02:14:34Z
• Authors: Hongqiao Zhang; Henry Jay Forman
• Keywords: Acrolein

Heme oxygenase-1 (HO-1) catalyzes the rate limiting reaction of heme metabolism and plays critical roles in resistance to oxidative stress other cellular functions. It is well known that HO-1 induced response various stresses; however, signaling pathways involved remain incompletely elucidated. Acrolein an alpha,beta-unsaturated aldehyde present cigarette smoke also a product lipid peroxidation. In this investigation we studied induction acrolein determined human bronchial epithelial cells (HBE1 cells). We demonstrated significantly increased mRNA content promoter activity. Acrolein-mediated was attenuated by pan-protein kinase C (PKC) inhibitors RO318220, staurosporine, PKC-delta selective inhibitor rottlerin small interfering RNA. The decreased phosphatidylinositol 3-kinase (PI3K) LY294002 wortmannin. No significant effects on were observed with pretreatment mitogen-activated protein pathway PD98059 (ERK), SB203580 (p38MAPK) JNKi, conventional atypical PKC inhibitors. Furthermore, Nrf2 silencing acrolein. Inhibition acrolein-mediated nuclear translocation, though inhibition PI3K had no effect. Taken together, our results indicate up-regulates expression through both HBE1 cells; appears regulate via modulating while may work targeting downstream molecules than Nrf2.