ERK and p38 Upregulation versus Bcl-6 Downregulation in Rat Kidney Epithelial Cells Exposed to Prolonged Hypoxia
نویسندگان
چکیده
Hypoxia is a common cause of kidney injury and a major issue in kidney transplantation. Mitogen-activated protein kinases (MAPKs) are involved in the cellular response to hypoxia, but the precise roles of MAPKs in renal cell reaction to hypoxic stress are not well known yet. This work was conducted to investigate the regulation of ERK1/2 and p38 and their signaling-relevant molecules in kidney epithelial cells exposed to prolonged hypoxia. Rat kidney epithelial cells NRK-52E were exposed to hypoxic conditions (1% O2) for 24-72 hrs. Cell morphology was examined by light microscopy, and cell viability was checked by MTS. The expression of ERK1/2 and p38 MAPK, as well as their signaling-related molecules, was measured by Western blot and RT-PCR. At the 1% oxygen level, cell morphology had no appreciable changes compared to the control up to 72 hrs of exposure under light microscopy, whereas the results of MTS showed a slight but significant reduction in cell viability after 72 hrs of hypoxia. On the other hand, ERK1/2 and p38 phosphorylation remarkably increased in these cells after 24-72 hrs of hypoxia. In sharp contrast, the expression of transcription factor B-cell lymphoma 6 (Bcl-6) was significantly downregulated in response to hypoxic stress. Other intracellular molecules relevant to the ERK1/2 and p38 signaling pathway, such as protein kinase A (PKA), protein kinase C (PKC), B-cell lymphoma 2 (Bcl-2), nuclear factor erythroid 2-related factor 2 (Nrf-2), tristetraprolin (TTP), and interleukin-10 (IL-10), had no significant alterations after 24-72 hrs of hypoxic exposure. We conclude that hypoxic stress increases the phosphorylation of both ERK1/2 and p38, but decreases the level of Bcl-6 in rat kidney epithelial cells.
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