Heme Arginate Pretreatment Attenuates Pulmonary NF-κB and AP-1 Activation Induced by Hemorrhagic Shock via Heme Oxygenase-1 Induction

Title: Heme Arginate Pretreatment Attenuates Pulmonary NF-κB and AP-1 Activation Induced by Hemorrhagic Shock via Heme Oxygenase-1 Induction

Volume: 2 Issue: 3

Author(s): M. Yokoyama, R. Akagi, K. Morita, M. Takeuchi, H. Morimatsu, Y. Toda, H. Shimizu, K. Maeshima, T. Sasaki and T. Takahashi

Affiliation:

Keywords: oxidative stress, nuclear factor-κB, inflammation, hemorrhagic shock, heme oxygenase-1, heme arginate, acute lung injury, Activator protein-1

Abstract: Hemorrhagic shock followed by resuscitation (HSR) induces oxidative stress that leads to acute lung injury. Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme catabolism, is induced by oxidative stress and is thought to play an important role in the protection from oxidative tissue injuries. We previously demonstrated that HO-1 induction by heme arginate (HA), a strong inducer of HO-1, ameliorated HSR-induced lung injury and inflammation. Cellular redox state is known to modulate the DNA biding activity of the transcription factors; nuclear factor-κB (NF-κB) and activator protein-1 (AP-1). In the present study, we treated rats with HA (30 mg/kg of hemin) 18 h prior to HSR and examined its effect on the DNA binding activity of NF-κB and AP-1 at 1.5 h after HSR. HSR significantly increased the DNA binding activity of NF-κB as well as AP-1, while HA pretreatment markedly attenuated the activities of these transcription factors. In contrast, administration of tin mesoporphyrin, a specific competitive inhibitor of HO activity, to HA-pretreated animals abolished the suppressive effect of HA on the activities of NF-κB and AP-1, and increased these activities to almost the same level as those in HSR animals. Our findings indicate that HA pretreatment can significantly suppress the increased activity of NF-κB and AP-1 induced by HSR by virtue of its ability to induce HO-1. Our findings also suggest that HO-1 induced by HA pretreatment ameliorates HSR-induced lung injury at least in part mediated through the suppression of the activities of these transcription factors.

Cite this article as:

Yokoyama M., Akagi R., Morita K., Takeuchi M., Morimatsu H., Toda Y., Shimizu H., Maeshima K., Sasaki T. and Takahashi T., Heme Arginate Pretreatment Attenuates Pulmonary NF-κB and AP-1 Activation Induced by Hemorrhagic Shock via Heme Oxygenase-1 Induction, Medicinal Chemistry 2006; 2 (3) . https://dx.doi.org/10.2174/157340606776930781