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Catalytic properties of the retinal rod outer segment disk ADP-ribosyl cyclase.
- Source :
-
Visual neuroscience [Vis Neurosci] 2011 Mar; Vol. 28 (2), pp. 121-8. Date of Electronic Publication: 2011 Jan 27. - Publication Year :
- 2011
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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 μM, 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, IC50=1.1 and 3.6 μM, 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.<br /> (Copyright © Cambridge University Press, 2011)
- Subjects :
- Animals
Calcium pharmacology
Cattle
Copper pharmacology
Dose-Response Relationship, Drug
Guanine Nucleotides metabolism
Microscopy, Electron, Transmission methods
Muscle, Skeletal enzymology
Muscle, Skeletal ultrastructure
NAD analogs & derivatives
NAD metabolism
Osmolar Concentration
Photic Stimulation
Rhodopsin metabolism
Rod Cell Outer Segment drug effects
Rod Cell Outer Segment ultrastructure
Sodium-Potassium-Exchanging ATPase metabolism
Zinc pharmacology
ADP-ribosyl Cyclase metabolism
Retina cytology
Retinal Rod Photoreceptor Cells cytology
Rod Cell Outer Segment enzymology
Subjects
Details
- Language :
- English
- ISSN :
- 1469-8714
- Volume :
- 28
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Visual neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 21269544
- Full Text :
- https://doi.org/10.1017/S0952523810000404