Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51812 (mitogen-activated protein)
 10,636 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this present study, we examined the role of Na(+)/H(+) exchanger 1 (NHE1) in the cultured rat vascular smooth muscle cell (VSMC) proliferation induced by advanced glycation end products (AGEs). AGEs significantly increased the [(3)H] thymidine incorporation of VSMC. Cariporide, an NHE1 inhibitor, dose-dependently attenuated the AGEs-induced increase in cell DNA synthesis. Thus the effect of AGEs on NHE1 activity was next examined. The cariporide-dependent intracellular pH (pH(i)) was significantly increased after 24h exposure to AGEs (10mug/ml). The direct AGEs-induced NHE1 activation was measured by the Na(+)-dependent intracellular pH recovery from intracellular acidosis. AGEs can increase the NHE1 activity in a time- and concentration-dependent manner. Inhibition of either the receptor for AGEs (RAGE) by anti-RAGE or mitogen-activated protein kinases (MAPK) by PD98059 reversed the effect of AGEs on NHE1 activity. Reverse transcription (RT)-PCR analysis revealed that AGEs dose-dependently increased NHE1 mRNA at 24h. These findings demonstrate NHE1 is required for in AGEs-induced proliferation of VSMC, and AGEs increase NHE1 activity via the MAPK pathway.
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PMID:Involvement of Na+/H+ exchanger 1 in advanced glycation end products-induced proliferation of vascular smooth muscle cell. 1870 17

The present study was undertaken to estimate the therapeutic benefit to down-regulate the Na(+)/H(+) exchanger 1 (NHE1) for reversing chemoresistance of BCR-ABL-positive leukemia patient cells and cell lines. As a result, after treatment with specific NHE1 inhibitor Cariporide or high K(+) buffer to decrease intracellular pH (pH(i)), cells from relapsed patients exhibited decreased Pgp level, enhanced Rhodamine123 and drug accumulation, decreased colony-forming ability and the modulations of mitogen-activated protein kinases (MAPKs) activities. Furthermore, we used BCR-ABL-positive cell line K562 and its resistant counterparts K562/DOX and K562/G01 cell lines for further study. Together, these findings suggest that Pgp may be associated with the reversal of drug resistance in BCR-ABL-positive leukemia patients and cell lines by the inhibition of NHE1 though MAPK pathways.
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PMID:Reversal of Imatinib resistance in BCR-ABL-positive leukemia after inhibition of the Na+/H+ exchanger. 2157 1