Modulation of store-operated ca2+ entry by cyclic-ADP-ribose

M. Thompson, T. White, Eduardo Nunes Chini

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Store-operated Ca2+ entry plays an important role in Ca2+ homeostasis in cells but the mechanisms of control of these channels are not completely understood. We describe an investigation of the role of the CD38-cyclic-ADP-ribose (cADPR)-ryanodine-channel (RyR) signaling pathway in store-operated Ca2+ entry in human smooth muscle. We observed that human myometrial cells have a functional store-operated Ca2+ entry mechanism. Furthermore, we observed the presence of transient receptor potential 1, 3, 4, 5, and 6 ion channels in human myometrial cells. Store-operated Ca2+ transient was inhibited by at least 50-70% by several inhibitors of the RyR, including ryanodine (10 μM), dantrolene (10 μM), and ruthenium red (10 μM). Furthermore, the cell permeable inhibitor of the cADPR-system, 8Br-cADPR (100 μM), is a potent inhibitor of the store-operated entry, decreasing the store operated entry by 80%. Pre-incubation of cells with 100 μM cADPR and the hydrolysis-resistant cADPR analog 3-deaza-cADPR (50 μM), but not with ADP-ribose (ADPR) leads to a 1.6-fold increase in the store-operated Ca2+ transient. In addition, we observed that nicotinamide (1-10 mM), an inhibitor of cADPR synthesis, also leads to inhibition of the store-operated Ca2+ transient by 50-80%. Finally, we observed that the transient receptor potential channels, RyR, and CD38 can be co-immunoprecipitated, indicating that they interact in vivo. Our observations clearly implicate the CD38-cADPR-ryanodine signaling pathway in the regulation of store-operated Ca2+ entry in human smooth muscle cells.

Original languageEnglish (US)
Pages (from-to)739-748
Number of pages10
JournalBrazilian Journal of Medical and Biological Research
Volume39
Issue number6
DOIs
StatePublished - Jun 2006

Fingerprint

Cyclic ADP-Ribose
ribose
Modulation
calcium
Ryanodine
Muscle
smooth muscle
cells
Cells
Adenosine Diphosphate Ribose
Dantrolene
Transient Receptor Potential Channels
Ruthenium Red
Niacinamide
nicotinamide
Ion Channels
ion channels
Smooth Muscle Myocytes
Smooth Muscle
Hydrolysis

Keywords

  • Calcium entry
  • Cyclic-ADP-ribose
  • Endoplasmic reticulum
  • Human smooth muscle
  • IP3
  • Ryanodine channel

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Medicine (miscellaneous)

Cite this

Modulation of store-operated ca2+ entry by cyclic-ADP-ribose. / Thompson, M.; White, T.; Chini, Eduardo Nunes.

In: Brazilian Journal of Medical and Biological Research, Vol. 39, No. 6, 06.2006, p. 739-748.

Research output: Contribution to journalArticle

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abstract = "Store-operated Ca2+ entry plays an important role in Ca2+ homeostasis in cells but the mechanisms of control of these channels are not completely understood. We describe an investigation of the role of the CD38-cyclic-ADP-ribose (cADPR)-ryanodine-channel (RyR) signaling pathway in store-operated Ca2+ entry in human smooth muscle. We observed that human myometrial cells have a functional store-operated Ca2+ entry mechanism. Furthermore, we observed the presence of transient receptor potential 1, 3, 4, 5, and 6 ion channels in human myometrial cells. Store-operated Ca2+ transient was inhibited by at least 50-70{\%} by several inhibitors of the RyR, including ryanodine (10 μM), dantrolene (10 μM), and ruthenium red (10 μM). Furthermore, the cell permeable inhibitor of the cADPR-system, 8Br-cADPR (100 μM), is a potent inhibitor of the store-operated entry, decreasing the store operated entry by 80{\%}. Pre-incubation of cells with 100 μM cADPR and the hydrolysis-resistant cADPR analog 3-deaza-cADPR (50 μM), but not with ADP-ribose (ADPR) leads to a 1.6-fold increase in the store-operated Ca2+ transient. In addition, we observed that nicotinamide (1-10 mM), an inhibitor of cADPR synthesis, also leads to inhibition of the store-operated Ca2+ transient by 50-80{\%}. Finally, we observed that the transient receptor potential channels, RyR, and CD38 can be co-immunoprecipitated, indicating that they interact in vivo. Our observations clearly implicate the CD38-cADPR-ryanodine signaling pathway in the regulation of store-operated Ca2+ entry in human smooth muscle cells.",
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AU - White, T.

AU - Chini, Eduardo Nunes

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N2 - Store-operated Ca2+ entry plays an important role in Ca2+ homeostasis in cells but the mechanisms of control of these channels are not completely understood. We describe an investigation of the role of the CD38-cyclic-ADP-ribose (cADPR)-ryanodine-channel (RyR) signaling pathway in store-operated Ca2+ entry in human smooth muscle. We observed that human myometrial cells have a functional store-operated Ca2+ entry mechanism. Furthermore, we observed the presence of transient receptor potential 1, 3, 4, 5, and 6 ion channels in human myometrial cells. Store-operated Ca2+ transient was inhibited by at least 50-70% by several inhibitors of the RyR, including ryanodine (10 μM), dantrolene (10 μM), and ruthenium red (10 μM). Furthermore, the cell permeable inhibitor of the cADPR-system, 8Br-cADPR (100 μM), is a potent inhibitor of the store-operated entry, decreasing the store operated entry by 80%. Pre-incubation of cells with 100 μM cADPR and the hydrolysis-resistant cADPR analog 3-deaza-cADPR (50 μM), but not with ADP-ribose (ADPR) leads to a 1.6-fold increase in the store-operated Ca2+ transient. In addition, we observed that nicotinamide (1-10 mM), an inhibitor of cADPR synthesis, also leads to inhibition of the store-operated Ca2+ transient by 50-80%. Finally, we observed that the transient receptor potential channels, RyR, and CD38 can be co-immunoprecipitated, indicating that they interact in vivo. Our observations clearly implicate the CD38-cADPR-ryanodine signaling pathway in the regulation of store-operated Ca2+ entry in human smooth muscle cells.

AB - Store-operated Ca2+ entry plays an important role in Ca2+ homeostasis in cells but the mechanisms of control of these channels are not completely understood. We describe an investigation of the role of the CD38-cyclic-ADP-ribose (cADPR)-ryanodine-channel (RyR) signaling pathway in store-operated Ca2+ entry in human smooth muscle. We observed that human myometrial cells have a functional store-operated Ca2+ entry mechanism. Furthermore, we observed the presence of transient receptor potential 1, 3, 4, 5, and 6 ion channels in human myometrial cells. Store-operated Ca2+ transient was inhibited by at least 50-70% by several inhibitors of the RyR, including ryanodine (10 μM), dantrolene (10 μM), and ruthenium red (10 μM). Furthermore, the cell permeable inhibitor of the cADPR-system, 8Br-cADPR (100 μM), is a potent inhibitor of the store-operated entry, decreasing the store operated entry by 80%. Pre-incubation of cells with 100 μM cADPR and the hydrolysis-resistant cADPR analog 3-deaza-cADPR (50 μM), but not with ADP-ribose (ADPR) leads to a 1.6-fold increase in the store-operated Ca2+ transient. In addition, we observed that nicotinamide (1-10 mM), an inhibitor of cADPR synthesis, also leads to inhibition of the store-operated Ca2+ transient by 50-80%. Finally, we observed that the transient receptor potential channels, RyR, and CD38 can be co-immunoprecipitated, indicating that they interact in vivo. Our observations clearly implicate the CD38-cADPR-ryanodine signaling pathway in the regulation of store-operated Ca2+ entry in human smooth muscle cells.

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KW - Ryanodine channel

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