| First Author | Nurbaeva MK | Year | 2012 |
| Journal | FASEB J | Volume | 26 |
| Issue | 7 | Pages | 3049-58 |
| PubMed ID | 22474243 | Mgi Jnum | J:187474 |
| Mgi Id | MGI:5437176 | Doi | 10.1096/fj.12-204024 |
| Citation | Nurbaeva MK, et al. (2012) Enhanced Ca(2)(+) entry and Na+/Ca(2)(+) exchanger activity in dendritic cells from AMP-activated protein kinase-deficient mice. FASEB J 26(7):3049-58 |
| abstractText | In dendritic cells (DCs), chemotactic chemokines, such as CXCL12, rapidly increase cytosolic Ca(2+)concentrations ([Ca(2+)](i)) by triggering Ca(2+) release from intracellular stores followed by store-operated Ca(2+) (SOC) entry. Increase of [Ca(2+)](i) is blunted and terminated by Ca(2+) extrusion, accomplished by K(+)-independent Na(+)/Ca(2+) exchangers (NCXs) and K(+)-dependent Na(+)/Ca(2+) exchangers (NCKXs). Increased [Ca(2+)](i) activates energy-sensing AMP-activated protein kinase (AMPK), which suppresses proinflammatory responses of DCs and macrophages. The present study explored whether AMPK participates in the regulation of DC [Ca(2+)](i) and migration. DCs were isolated from AMPKalpha1-deficient (ampk(-/-)) mice and, as control, from their wild-type (ampk(+/+)) littermates. AMPKalpha1, Orai1-2, STIM1-2, and mitochondrial calcium uniporter protein expression was determined by Western blotting, [Ca(2+)](i) by Fura-2 fluorescence, SOC entry by inhibition of endosomal Ca(2+) ATPase with thapsigargin (1 muM), Na(+)/Ca(2+) exchanger activity from increase of [Ca(2+)](i), and respective whole-cell current in patch clamp following removal of extracellular Na(+). Migration was quantified utilizing transwell chambers. AMPKalpha1 protein is expressed in ampk(+/+) DCs but not in ampk(-/-) DCs. CXCL12 (300 ng/ml)-induced increase of [Ca(2+)](i), SOC entry, Orai 1 protein abundance, NCX, and NCKX were all significantly higher in ampk(-/-) DCs than in ampk(+/+) DCs. NCX and NCKX currents were similarly increased in ampk(-/-) DCs. Moreover, CXCL12 (50 ng/ml)-induced DC migration was enhanced in ampk(-/-) DCs. AMPK thus inhibits SOC entry, Na(+)/Ca(2+) exchangers, and migration of DCs. |
