Role of p38MAPK, heat shock proteins, HSP27 and HSP70 in osmotic stress in renal vs. blood cells: A comparative study

It has been observed that osmotic stress induces various changes in different cell types. Mammalian kidney cells are normally exposed to high osmotic concentrations as a consequence of their participation in the urinary concentration mechanism (Natalia et al., 2005). Cell structure and volume dependent remodeling of cytoskeleton is known to be influenced as an adaptive response to withstand high osmotic stress (Di Ciano et al., 2002). We investigated the role and induction of p38MAPK and Heat Shock Proteins (HSPs) in both human hematopoietic and mouse kidney cells (cortical and medullary) in response to sodium chloride induced hyperosmotic stress. Inhibitors of p38 MAPK and HSPs were used to define their contributions to hyperosmotic stress. Acute stress led to increased p38 MAPK and HSP27 mRNA levels in the human hematopoietic cell line whereas an upregulation of p38MAPK mRNA in the cortical cells of kidney and an increase in HSP70.1 mRNA levels in the medullary cells of kidney was observed. Using RT-PCR and Western immunoblotting both mRNA and protein levels of heat shock proteins, HSP27 and HSP70 were quantified. The p38MAPK inhibitor, SB203580 inhibited the induction of HSP70 in the medullary cells. In addition, HSP inhibitor, KNK-437 also inhibited the p38MAPK levels thereby suggesting that both HSP70 and p38MAPK are required for each other's induction and activation in the hyperosmotically stressed medullary cells of the kidney. Since the p38MAPK levels were inhibited in the cortical cells in presence of KNK-437, it suggests that HSP70 plays a role in induction of p38MAPK in these cells. Studies with mIMCD-3 cells, the inner medullary collecting duct cell line and M-1, the cortical cell line from mouse, indicate that cells from different parts of the kidney respond differently to high osmotic stress.