| First Author | Zou J | Year | 2013 |
| Journal | Am J Physiol Cell Physiol | Volume | 305 |
| Issue | 1 | Pages | C61-9 |
| PubMed ID | 23596170 | Mgi Jnum | J:202791 |
| Mgi Id | MGI:5521451 | Doi | 10.1152/ajpcell.00390.2012 |
| Citation | Zou J, et al. (2013) A differential role of macrophage TRPM2 channels in Ca(2)(+) signaling and cell death in early responses to H(2)O(2). Am J Physiol Cell Physiol 305(1):C61-9 |
| abstractText | Reactive oxygen species such as H(2)O(2) elevates the cytosolic Ca(2)(+) concentration ([Ca(2)(+)]c) and causes cell death via poly(ADPR) polymerase (PARP) activation, which also represents the primary mechanism by which H(2)O(2) activate the transient receptor potential melastatin-related 2 (TRPM2) channel as a Ca(2)(+)-permeable channel present in the plasma membrane or an intracellular Ca(2)(+)-release channel. The present study aimed to define the contribution and mechanisms of the TRPM2 channels in macrophage cells in mediating Ca(2)(+) signaling and cell death during initial response to H(2)O(2), using mouse peritoneal macrophage, RAW264.7, and differentiated THP-1 cells. H(2)O(2) evoked robust increases in the [Ca(2)(+)]c, and such Ca(2)(+) responses were significantly greater at body temperature than room temperature. H(2)O(2)-induced Ca(2)(+) responses were strongly inhibited by pretreatment with PJ-34, a PARP inhibitor, and largely prevented by removal of extracellular Ca(2)(+). Furthermore, H(2)O(2)-induced increases in the [Ca(2)(+)]c were completely abolished in macrophage cells isolated from trpm2-/- mice. H(2)O(2) reduced macrophage cell viability in a duration- and concentration-dependent manner. H(2)O(2)-induced cell death was significantly attenuated by pretreatment with PJ-34 and TRPM2 channel deficiency but remained significant and persistent. Taken together, these results show that the TRPM2 channel in macrophage cells functions as a cell surface Ca(2)(+)-permeable channel that mediates Ca(2)(+) influx and constitutes the principal Ca(2)(+) signaling mechanism but has a limited, albeit significant, role in cell death during early exposure to H(2)O(2). |
