In:
Visual Neuroscience, Cambridge University Press (CUP), Vol. 28, No. 2 ( 2011-03), p. 121-128
Abstract:
Cyclic ADP-ribose (cADPR) is a second messenger modulating intracellular calcium levels. We have previously described a cADPR-dependent calcium signaling pathway in bovine rod outer segments (ROS), where calcium ions play a pivotal role. ROS ADP-ribosyl cyclase (ADPR-cyclase) was localized in the membrane fraction. In the present work, we examined the properties of the disk ADPR-cyclase through the production of cyclic GDP-ribose from the NAD + analogue NGD + . The enzyme displayed an estimated K m for NGD + of 12.5 ± 0.3 μ M, a V max of 26.50 ± 0.70 pmol cyclic GDP-ribose synthesized/min/mg, and optimal pH of 6.5. The effect of divalent cations (Zn 2+ , Cu 2+ , and Ca 2+ ) was also tested. Micromolar Zn 2+ and Cu 2+ inhibited the disk ADPR-cyclase activity (half maximal inhibitory concentration, IC 50 = 1.1 and 3.6 μ M, respectively). By contrast, Ca 2+ ions had no effect. Interestingly, the properties of the intracellular membrane–associated ROS disk ADPR-cyclase are more similar to those of the ADPR-cyclase found in CD38-deficient mouse brain, than to those of CD38 or CD157. The novel intracellular mammalian ADPR-cyclase would elicit Ca 2+ release from the disks at various rates in response to change in free Ca 2+ concentrations, caused by light versus dark adaptation, in fact there was no difference in disk ADPR-cyclase activity in light or dark conditions. Data suggest that disk ADPR-cyclase may be a potential target of retinal toxicity of Zn 2+ and may shed light to the role of Cu 2+ and Zn 2+ deficiency in retina.
Type of Medium:
Online Resource
ISSN:
0952-5238
,
1469-8714
DOI:
10.1017/S0952523810000404
Language:
English
Publisher:
Cambridge University Press (CUP)
Publication Date:
2011
detail.hit.zdb_id:
1489922-X
SSG:
12
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