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- Title
P-ERK Activation by Extracellular or Intracellular Acidosis Slows NHE3-Mediated Acid Extrusion And Activates Ammoniagenesis in LLC-PK1-F+ Cells.
- Authors
Oliver III, Robert Earl; Kaur, Primal; Turturro, Francesso; Friday, Ellen; Welbourne, Tomas
- Abstract
We exposed proximal tubule-like F+ cells to extracellular acidosis pHo=6.8 or troglitazone (TRO)-induced intracellular acidosis pHi<6.8(pHo=7.4) for 4min and 3h in order to determine cell signaling and physiological responses (NHE3 activity and NH4+production). Exposure to pHo =6.8 for 4min and 3h reduced the pHi from 7.32 ±0.07 to 6.96±0.04 and 6.75±0.11 associated with a 2.3 and 2.7 fold rise in PERK/ T-ERK ratio (both p<0.05). Exposure to TRO (20uM) reduced pHi from 7.32±0.07 to 6.60±0.08 and 6.86±0.15 associated with a 3.7 and 2.1 rise in P-ERK at 4min and 3h respectively. NHE3 activity measured after transient 6min exposure to pHo=6.8 was reduced by 32% (p<0.01) while NH4+ increased by 1.65 fold (p<0.05) at 3h; TRO reduced NHE3 activity by 82% and NH4+ 2.4 fold (both p<0.01). TRO-induced P-ERK activation and fall in pHi was prevented by inhibiting EGFR in contrast EGFR inhibition with pHo 6.8 did not decrease P-ERK activation or cellular acidosis. Pre-incubation with MEKK inihibitors PD98059 and UO126 prevented the acidosis-induced increase in P-ERK and ammoniagenesis. Our results are consonant with P-ERK activation associated with extracellular acidosis and intracellular acidosis (K+ deficiency?) playing a major role in regulating acute physiological responses.
- Subjects
PROTEIN kinases; ACTIVATION (Chemistry); ACIDOSIS; AMMONIA; CELLS
- Publication
FASEB Journal, 2007, Vol 21, Issue 6, pA1414
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fasebj.21.6.a1414-c