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Departments of Obstetrics and Gynecology, Physiology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan
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& Vale 2006 ). Urocortin 2 (Ucn2) is a member of the CRF peptide family, which acts through binding to CRF type 2 receptor (CRF-R2). Others and we previously demonstrated that Ucn2 is expressed in both the brain and peripheral tissues, including the lung
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actions of CRF are induced through two subtypes of CRF receptor (CRF-R), the CRF-R1 and the CRF-R2, with a higher affinity to CRF-R1 than to CRF-R2 ( Chen et al . 1993 , Perrin et al . 1993 , Lovenberg et al . 1995 a ). Urocortins 2 (Ucn 2), one of
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& Vale W 2004 Urocortin II gene is highly expressed in mouse skin and skeletal muscle tissues: localization, basal expression in corticotropin-releasing factor receptor (CRFR) 1- and CRFR2-null mice, and regulation by glucocorticoids. Endocrinology
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Introduction Emerging evidence suggests that the urocortin (UCN) peptides UCN1, UCN2, and UCN3, recently identified members of the corticotropin-releasing factor (CRF) peptide family, contribute to pressure and volume regulation with possible
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We have previously demonstrated that urocortin protects cultured cardiac myocytes from ischaemic and reoxygenation injury and decreases the infarct size in the rat heart exposed to regional ischaemia and reperfusion. Urocortin-mediated cardioprotection is via activation of the mitogen-activated protein kinase (MAP kinase, MEK1/2) pathway. In addition, it is well documented that heat shock protein (hsp) 70 and hsp90 are cardioprotective against lethal stress. In this study we show, for the first time, that urocortin induces the expression of hsp90 but not hsp70 in primary cultures of rat neonatal cardiac myocytes. Levels of hsp90 protein increase by 1.5-fold over untreated cells within 10 min of urocortin treatment and are sustained for 24 h with a maximal increase of 2.5-fold at 60 min (P<0.05 at all time points). The increase in hsp90 expression by urocortin was not inhibited by actinomycin D, and urocortin failed to increase hsp90 promoter activity. Urocortin induction of hsp90 was inhibited by the MEK1/2 inhibitor PD98059 (P<0.001) and by cycloheximide, and both inhibitors abrogate urocortin-mediated cardioprotection (P<0.05 for cycloheximide, P<0.001 for PD98059). Hence, MEK1/2 and protein synthesis are involved in the cardioprotective effect of urocortin against hypoxic-mediated cell death, possibly due to an increase in expression of hsp90 protein. This is the first report of heat shock protein induction by urocortin or any other member of the corticotrophin-releasing hormone family.
Department of Biological Chemistry, University of Michigan, 109 Zina Pitcher Place, BSRB Room 5035, Ann Arbor, Michigan 48109, USA
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Department of Psychiatry, University of Michigan, 109 Zina Pitcher Place, BSRB Room 5035, Ann Arbor, Michigan 48109, USA
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peptides have also been shown to modulate gonadotropin levels by acting at the pituitary (reviewed in Evans (1999) ). Thus, CRH and other members of the CRH family of peptides, urocortin (UCN), urocortin 2 (UCN2), and urocortin 3 (UCN3), may participate in
Department of Ophthalmology, University of Tennessee Health Science Center, 930 Madison Avenue, RM525, Memphis, Tennessee 38163, USA
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Department of Ophthalmology, University of Tennessee Health Science Center, 930 Madison Avenue, RM525, Memphis, Tennessee 38163, USA
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Department of Ophthalmology, University of Tennessee Health Science Center, 930 Madison Avenue, RM525, Memphis, Tennessee 38163, USA
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, Chrousos 1995 , Aguilera 1998 ). Physiological actions of CRF and related peptides such as urocortins I–III (Ucn I–III) are mediated through interactions with membrane-bound receptors, CRFR1 and CRFR2 ( Perrin & Vale 1999 , Grammatopoulos & Chrousos 2002
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Introduction The corticotropin-releasing hormone (CRH) peptide family comprises CRH and the structurally related urocortin peptides (UCN1, UCN2 and UCN3). These neuroendocrine peptides are best known for their involvement in regulating the
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Department of General Medicine, Asahikawa Medical University, Asahikawa, Hokkaido, Japan
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urocortin 2, a selective CRF 2 agonist (Bachem AG, Bubendorf, Switzerland), LPS obtained from Escherichia coli with the serotype 055:B5 (Sigma-Aldrich) and anakinra, an IL-1 receptor antagonist (Swedish Orphan Biovitrum, Stockholm, Sweden) were dissolved
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TM Gulyas J Fischer W 2001 Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor . PNAS 98 7570 – 7575 . doi:10.1073/pnas.121165198 . Lovenberg
