| First Author | Moon MY | Year | 2013 |
| Journal | Cell Signal | Volume | 25 |
| Issue | 9 | Pages | 1861-9 |
| PubMed ID | 23707391 | Mgi Jnum | J:318985 |
| Mgi Id | MGI:6862205 | Doi | 10.1016/j.cellsig.2013.05.023 |
| Citation | Moon MY, et al. (2013) Involvement of small GTPase RhoA in the regulation of superoxide production in BV2 cells in response to fibrillar Abeta peptides. Cell Signal 25(9):1861-9 |
| abstractText | Fibrillar amyloid-beta (fAbeta) peptide causes neuronal cell death, which is known as Alzheimer's disease. One of the mechanisms for neuronal cell death is the activation of microglia which releases toxic compounds like reactive oxygen species (ROS) in response to fAbeta. We observed that fAbeta rather than soluble form blocked BV2 cell proliferation of microglial cell line BV2, while N-acetyl-l-cysteine (NAC), a scavenger of superoxide, prevented the cells from death, suggesting that cell death is induced by ROS. Indeed, both fAbeta1-42 and fAbeta25-35 induced superoxide production in BV2 cells. fAbeta25-35 produced superoxide, although fAbeta25-35 is not phagocytosed into BV2 cells. Thus, superoxide production by fAbeta does not seem to be dependent on phagocytosis of fAbeta. Herein we studied how fAbeta produces superoxide in BV2. Transfection of dominant negative (DN) RhoA (N19) cDNA plasmid, small hairpin (sh)-RhoA forming plasmid, and Y27632, an inhibitor of Rho-kinase, abrogated the superoxide formation in BV2 cells stimulated by fAbeta. Furthermore, fAbeta elevated GTP-RhoA level as well as Rac1 and Cdc42. Tat-C3 toxin, sh-RhoA, and Y27632 inhibited the phosphorylation of p47(PHOX). Moreover, peritoneal macrophages from p47(PHOX) (-/-) knockout mouse could not produce superoxide in response to fAbeta. These results suggest that RhoA closely engages in the regulation of superoxide production induced by fAbeta through phosphorylation of p47(PHOX) in microglial BV2 cells. |
