| First Author | Tano JY | Year | 2012 |
| Journal | Biochem Biophys Res Commun | Volume | 427 |
| Issue | 1 | Pages | 178-84 |
| PubMed ID | 22989752 | Mgi Jnum | J:190105 |
| Mgi Id | MGI:5448083 | Doi | 10.1016/j.bbrc.2012.09.038 |
| Citation | Tano JY, et al. (2012) Involvement of calmodulin and calmodulin kinase II in tumor necrosis factor alpha-induced survival of bone marrow derived macrophages. Biochem Biophys Res Commun 427(1):178-84 |
| abstractText | We previously showed that survival signaling in TNFalpha-treated, human THP1-derived macrophages (TDMs) has an obligatory requirement for constitutive Ca(2+) influx through a mechanism involving calmodulin/calmodulin kinase II (CAM/CAMKII). We also demonstrated that such requirement also applies to the protective actions of TNFalpha in murine bone marrow-derived macrophages (BMDMs) and that TRPC3 channels mediate constitutive Ca(2+) influx. Using a pharmacological approach we here examined if in BMDMs, similarly to TDMs, TNFalpha-induced survival signaling also involves CAM/CAMKII. In BMDMs, TNFalpha induced rapid activation of the survival pathways NFkappaB, AKT and p38MAPK. All these routes were activated in a PI3K-dependent fashion. Activation of AKT and NFkappaB, but not that of p38MAPK, was abrogated by the CAM inhibitor W7, while KN-62, a CAMKII inhibitor, prevented activation of AKT and p38MAPK but not that of NFkappaB. Inhibition of CAM or CAMKII completely prevented the protective actions of TNFalpha. Our observations indicate that in BMDMs CAM and CAMKII have differential contributions to the components of TNFalpha-dependent survival signaling and underscore a complex interplay among canonical survival routes. These findings set a signaling framework to understand how constitutive Ca(2+) influx couples to macrophage survival in BMDMs. |
