CHARACTERIZATION OF THE HSP110 SSE GENE FAMILY RESPONSE TO HYPEROSMOLALITY AND OTHER STRESSES/

Hsp110, Osp94, and Hsp70RY are members of the recently described Hsp11 0/SSE subfamily of (heat and osmotic) stress proteins whose members ar e structurally related to the Hsp70/BiP gene superfamily. To date, lit tle is known about the response of this gene family to stresses in vit ro or in vivo. In this study, an analysis of mRNA expression showed th at Hsp110 and Osp94, like Hsp70, are induced in renal murine inner med ullary collecting duct (mIMCD3) epithelial cells by heat shock, hypero smotic NaCl, and cadmium, whereas low pH had a suppressive effect on O sp94. H2O2 decreased expression of Osp94 while inducing levels of Hsp1 10 and Hsp70 message. Tunicamycin, hypertonic urea, and tumor necrosis factor-alpha had no effects. Hsp70RY was responsive exclusively to ca dmium chloride. Moreover, enhanced expression of Hsp110 and Osp94 was subsequent to induction of Hsp70 and was suppressed by inhibition of p rotein synthesis by cycloheximide. RT-PCR analysis showed Hsp110, Osp9 4, and Hsp70RY are ubiquitously expressed in mouse tissues. In murine kidney, there was a corticomedullary gradient of expression of Hsp110, Osp94, Hsp70RY, and Hsp70 but not Hsc70 or BiP. Furthermore, dehydrat ion increased inner medullary expression of Hsp110 and Osp94. An analy sis of stress tolerance in mIMCD3 cells showed that heat shock and hyp erosmotic NaCl stress are cross-tolerant stresses, suggesting hyperosm olality is a physiological correlate of heat shock in mammalian kidney . Thus Hsp110 and Osp94 behave as heat shock proteins, although they a re regulated differently than Hsp70.