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Differential actions of Pioglitazone (PIO) and Rosiglitazone (RGZ) on proximal tubule‐like cells
Author(s) -
Oliver Robert,
Friday Ellen,
Turturro Francesco,
Welbourne Tomas
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.834.4
Kidney PT cells account for the reabsorption of the bulk of filtered Na + in part mediated by NHE3. PIO and RGZ were studied in LLC‐PK1 cells for their actions on NHE activity and anaplerosis. PIO (10uM) but not RGZ (25uM) for 24h reduced NHE3 activity (90±13 to 55±6 pHi /min x10 3 , p<0.05) which could be reversed (120±13, p<0.01) with 10uM GW9662 consistent with preventing PPARγ mediated down‐regulation. GW9662 increased NHE3 but not NHE1 mRNA. GW9662 reversal of PIO's affect could be blocked with the NHE3 inhibitor S3226 (48±6, p<0.01)) added directly in the media. In contrast to PIO, RGZ did not reduce NHE3 activity unless present in the media. RGZ activated anaplerosis from glutaminolysis, increasing NH 4 + (4.5±0.3 vs. 3.1±0.2 umol/mg, p<0.01) while reducing ALA (5.4±0.2 vs 7.3±0.5 umol/mg, p<0.01) and increasing lactate production (12.3±0.2 vs 9.9±0.7umol/mg, p<0.05) whereas PIO only increased NH 4 + (3.7±0.1,p<0.05). GW9662 did not block RGZ's increased glutaminolysis, increased NH 4 + or decreased ALA. GW9662 prevented PIO increased NH 4 + (2.7±0.2 vs 3.7±0.1,p<0.05) associated with increased pHi (7.28±0.07; 7.08±0.09,p<0.05, and 7.26±0.05 ctl; PIO; and PIO+GW9662). PIO may act via PPARγ to down regulate Na + reabsorption and H + / NH 4 + extrusion while RGZ may act via anaplerosis to affect the opposite. Research support: Southern Arizona Research Foundation (TW) and Feist‐ Weiller Cancer Center (FT)