cADP-ribose/ryanodine channel/Ca2+-release signal transduction pathway in mesangial cells

Signaling via release of Ca2+ from intracellular stores is mediated by several systems, including the inositol 1,4,5-trisphosphate (IP3) and cADP-ribose (cADPR) pathway. We recently discovered a high capacity for cADPR synthesis in rat glomeruli and cultured mesangial cells (MC). We sought to determ...

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Bibliographic Details
Published in:American journal of physiology. Renal physiology 2001-07, Vol.281 (1), p.F91-F102
Main Authors: Yusufi, A N, Cheng, J, Thompson, M A, Dousa, T P, Warner, G M, Walker, H J, Grande, J P
Format: Article
Language:English
Subjects:
Adenosine Diphosphate Ribose - analogs & derivatives
Adenosine Diphosphate Ribose - pharmacology
ADP-ribosyl Cyclase
ADP-ribosyl Cyclase 1
Animals
Antigens, CD
Antigens, Differentiation - metabolism
Calcium - metabolism
Cations, Divalent
Cells, Cultured
Cyclic ADP-Ribose
Glomerular Mesangium - drug effects
Glomerular Mesangium - metabolism
Interleukin-1 - pharmacology
Lipopolysaccharides - pharmacology
Male
Membrane Glycoproteins
NAD+ Nucleosidase - metabolism
Rats
Rats, Sprague-Dawley
Ryanodine Receptor Calcium Release Channel - metabolism
Signal Transduction
Tretinoin - pharmacology
Triiodothyronine - pharmacology
Tumor Necrosis Factor-alpha - pharmacology
Up-Regulation
Vasopressins - pharmacology
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Summary:Signaling via release of Ca2+ from intracellular stores is mediated by several systems, including the inositol 1,4,5-trisphosphate (IP3) and cADP-ribose (cADPR) pathway. We recently discovered a high capacity for cADPR synthesis in rat glomeruli and cultured mesangial cells (MC). We sought to determine whether 1) cADPR synthesis in MC is regulated by cytokines and hormones, 2) ryanodine receptors (RyRs) are expressed in MC, and 3) Ca2+ is released through RyRs in response to cADPR. We found that ADP-ribosyl cyclase, a CD38-like enzyme that catalyzes cADPR synthesis, is upregulated in MC by tumor necrosis factor-alpha, interleukin-1beta, and all-trans retinoic acid (atRA). [3H]ryanodine binds to microsomal fractions from MC with high affinity in a Ca2+-dependent manner; binding is enhanced by specific RyR agonists and blocked by ruthenium red and cADPR. Western blot analysis confirmed the presence of RyR in MC. Release of 45Ca2+ from MC microsomes was stimulated by cADPR; release was blocked by ruthenium red and 8-bromo-cADPR. ADPR (non-cyclic) was without effect. In MC, TNF-alpha and atRA amplified the increment of cytoplasmic Ca2+ elicited by vasopressin. We conclude that MC possess elements of a novel ADP-ribosyl cyclase-->cADPR-->RyR-->Ca2+-release signaling pathway subject to regulation by proinflammatory cytokines and steroid superfamily hormones.
ISSN:1931-857X
DOI:10.1152/ajprenal.2001.281.1.F91