Regulation of heat shock protein 70 (hsp 70) by parathyroid hormone
(pth): a model of gene regulation not regulated by changes in cyclic
amp levels.
Fukayama, Shoichi, Beate Lanske, Jun Guo, Henry M. Kronenberg, and F.
Richard Bringhurst.
Endocrine Unit, Massachusetts General Hospital, and Department of
Medicine, Harvard Medical School, Boston MA 02114
APStracts 3:0022C, 1996.
Parathyroid hormone (PTH) activates both adenylate cyclase and
phospholipase-C in target cells, and cloned PTH/PTHrP receptor can
mediate both responses when expressed in host cells such as LLC-PK1
renal epithelial cells. Because calcitonin (CT) is known to augment
HSP 70 mRNA by a cAMP-independent mechanism in LLC-PK1 cells, we
examined regulation of HSP 70 transcription by PTH in these cells.
Like CT, hPTH(1-34) (10-10 - 10-7 M) increased porcine HSP 70 mRNA
and human HSP 70 promoter-CAT expression within 4 h in LLC-PK1 cells
that stably express 100,000 or more PTH/PTHrP receptors/cell. The
effect of PTH on HSP 70 mRNA was not mimicked by cAMP analogs,
forskolin, phorbol esters, calcium ionophores or [alpha]-thrombin,
was insensitive to pertussis toxin, and was not due to increased mRNA
stability. The upregulation of HSP 70 gene transcription by hPTH (and
CT) was clearly observed even after deletion of the functional heat
shock consensus element (HSE) in the promoter region of the human HSP
70/CAT reporter. Upregulation of HSP 70 transcription via endogenous
PTH receptors also was observed in the osteoblastic cell lines SaOS-2
and ROS 17/2.8. Regulation of HSP 70 gene transcription by PTH may be
a common cellular response to the hormone which, in some cells, may
not be mediated by activation of adenylate cyclase or protein kinase
C.
Received 9 May 1995; accepted in final form 15 December 1995.
APS Manuscript Number C263-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 January 96