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1 Renal Division, Department of Medicine, Brigham and Women's Hospital and Harvard Institutes of Medicine, Boston, Massachusetts 02115; and 2 Department of Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya 468, Japan
Hsp110, Osp94,
and Hsp70RY are members of the recently described Hsp110/SSE subfamily
of (heat and osmotic) stress proteins whose members are structurally
related to the Hsp70/BiP gene superfamily. To date, little
is known about the response of this gene family to stresses in vitro or
in vivo. In this study, an analysis of mRNA expression showed that
Hsp110 and Osp94, like Hsp70, are induced in renal murine inner
medullary collecting duct (mIMCD3) epithelial cells by heat shock,
hyperosmotic NaCl, and cadmium, whereas low pH had a suppressive effect
on Osp94.
H2O2
decreased expression of Osp94 while inducing levels of Hsp110 and Hsp70 message. Tunicamycin, hypertonic urea, and tumor necrosis factor-
had no effects. Hsp70RY was responsive exclusively to cadmium chloride.
Moreover, enhanced expression of Hsp110 and Osp94 was subsequent to
induction of Hsp70 and was suppressed by inhibition of protein
synthesis by cycloheximide. RT-PCR analysis showed Hsp110, Osp94, 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, dehydration
increased inner medullary expression of Hsp110 and Osp94. An analysis
of stress tolerance in mIMCD3 cells showed that heat shock and
hyperosmotic NaCl stress are cross-tolerant stresses, suggesting
hyperosmolality is a physiological correlate of heat shock in mammalian
kidney. Thus Hsp110 and Osp94 behave as heat shock proteins, although
they are regulated differently than Hsp70.
heat stress protein 70; BiP binding protein; heat shock; stress tolerance; kidney; molecular chaperone
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