Hypoxic Stress-Enhanced
Expression and Release of Adrenomedullin (AM) and Up-Regulated
AM Receptors, while Glucose Starvation Reduced AM Expression and
Release and Down-Regulated AM Receptors in Monkey Renal Cells
J. DŘÍMAL1, J. DŘÍMAL JR.2,
D. DŘÍMAL3
1Institute of Experimental Pharmacology, Slovak
Academy of Sciences, Bratislava, 2Department of
Information Technology, Slovak Gas Industry, Bratislava,
3Faculty of Material Science and Technology, Slovak University
of Technology, Bratislava, Slovak Republic
Received date August 4, 2005
Accepted date November 21, 2005
On-line available December 12, 2005
Summary
The proliferative peptide adrenomedullin (AM) has a wide
distribution in a variety of tissues and cells. The mechanism
how the AM gene is regulated in cells is not yet known. The
renal cortex, renal vascular smooth muscles, glomeruli and
tubular epithelial cells are very sensitive to hypoxia. Renal
hypoxia produces acute renal tubular necrosis and markedly
induces AM expression in damaged cells. However, little
information is available regarding the possible
pathophysiological production and release of renal tubular AM.
Regulation of membrane-bound AM receptors in renal cells has not
yet been systematically studied. To elucidate the potential
pathological role of human AM we examined the production and
release of AM, as well as the characteristics of surface
membrane AM receptors in cultured monkey renal tubular
epithelial cells (RC) exposed to hypoxia, induced with
endothelin-1, and subjected to glucose deprivation. Exposure of
RC to hypoxia (1 % O2, 5 % CO2 in N2), and to phorbol
12-myristate 13-acetate (PMA) increased production and secretion
of AM and increased specific [125I]AM binding on RC. Metabolic
stress (1 % glucose in the cultivation medium) and preincubation
of RC with rival peptide endothelin-1 significantly reduced
immunoreactive-AM in a conditioned medium and whole cell surface
membrane AM binding on RC. Altogether, our data suggest that the
AM is involved in the adaptation of renal tubular cells to
hypoxia. Increased expression of AM mRNA and regulation of AM
receptors in metabolic stress may function as an important
autocrine/paracrine regulator(s) of renal tubular epithelial
cells.
Key words
Adrenomedullin expression and release • Ligand binding studies •
Renal tubular epithelial cells • Radioimmunoassays • Hypoxia •
Glucose repression
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