サイクリックADPリボース

関: cADPR、cyclic ADPR

WordNet

of a compound having atoms arranged in a ring structure
recurring in cycles (同)cyclical
conforming to the Carnot cycle
forming a whorl or having parts arranged in a whorl; "cyclic petals"; "cyclic flowers"
marked by repeated cycles
the 1st letter of the Roman alphabet (同)a
the blood group whose red cells carry the A antigen (同)type_A, group A
a pentose sugar important as a component of ribonucleic acid
in the Christian era; used before dates after the supposed year Christ was born; "in AD 200" (同)A.D., anno_Domini

PrepTutorEJDIC

answer / ampere
リボース(リボ核酸の加水分解によって得られる五炭糖)

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/03/22 02:40:22」(JST)

wiki en

[Wiki en表示]

Cyclic ADP Ribose, frequently abbreviated as cADPR, is a cyclic adenine nucleotide (like cAMP) with two phosphate groups present on 5' OH of the adenosine (like ADP), further connected to another ribose at the 5' position, which, in turn, closes the cycle by glycosidic bonding to the nitrogen 1 (N¹) of the same adenine base (whose position N⁹ has the glycosidic bond to the other ribose).^[1]^[2] The N¹-glycosidic bond to adenine is what distinguishes cADPR from ADP-ribose (ADPR), the non-cyclic analog. cADPR is produced from nicotinamide adenine dinucleotide (NAD⁺) by ADP-ribosyl cyclases (EC 3.2.2.5) as part of a second messenger system.

Function

cADPR is a cellular messenger for calcium signaling.^[3] It stimulates calcium-induced calcium release at lower cytosolic concentrations of Ca²⁺. Primary target of cADPR is the ER Ca2+ uptake mechanism. Potentiation of Ca2+ release by cADPR is mediated by increased accumulation of Ca2+ in the SR and subsequent luminal Ca2+-dependent activation of ryanodine receptors (RyRs).^[4] Some reports suggest that cADPR binding makes FKBP12.6, which normally binds RyR2, to fall off the RYR2.

Metabolism

cADPR and ADPR are synthesized from NAD⁺ by the bifunctional ectoenzymes of the CD38 family (also includes the GPI-anchored CD157 and the specific, monofunctional ADP ribosyl cyclase of the mollusc Aplysia).^[5]^[6]^[7] The same enzymes are also capable of hydrolyzing cADPR to ADPR. Catalysis proceeds via a covalently bound intermediate. The hydrolysis reaction is inhibited by ATP, and cADPR may accumulate. Synthesis and degradation of cADPR by enzymes of the CD38 family involve, respectively, the formation and the hydrolysis of the N¹-glycosidic bond. In 2009, the first enzyme able to hydrolyze the phosphoanhydride linkage of cADPR, i.e. the one between the two phosphate groups, has been reported.^[8]

References

^ Lee HC, Walseth TF, Bratt GT, Hayes RN, Clapper DL (1989). "Structural determination of a cyclic metabolite of NAD⁺ with intracellular Ca²⁺-mobilizing activity". J. Biol. Chem. 264 (3): 1608–15. PMID 2912976.
^ Lee HC, Aarhus R, Levitt D (1994). "The crystal structure of cyclic ADP-ribose". Nat. Struct. Biol. 1 (3): 143–4. doi:10.1038/nsb0394-143. PMID 7656029.
^ Guse AH (2004). "Regulation of calcium signaling by the second messenger cyclic adenosine diphosphoribose (cADPR)". Curr. Mol. Med. 4 (3): 239–48. doi:10.2174/1566524043360771. PMID 15101682.
^ Lukyanenko V, Györke I, Wiesner TF, Györke S. 2001. Potentiation of Ca(2+) release by cADP-ribose in the heart is mediated by enhanced ER Ca2+ uptake into the sarcoplasmic reticulum. Circ Res. 89(7):614-22. PMID 11577027; 10.1161/hh1901.098066
^ Prasad GS, McRee DE, Stura EA, Levitt DG, Lee HC, Stout CD (1996). "Crystal structure of Aplysia ADP-ribosyl cyclase, a homolog of the bifunctional ectozyme CD38". Nat. Struct. Biol. 3 (11): 957–64. doi:10.1038/nsb1196-957. PMID 8901875.
^ Liu Q, Kriksunov IA, Graeff R, Munshi C, Lee HC, Hao Q (2005). "Crystal structure of the human CD38 extracellular domain". Structure 13 (9): 1331–9. doi:10.1016/j.str.2005.05.012. PMID 16154090.
^ Guse AH (2004). "Biochemistry, biology, and pharmacology of cyclic adenosine diphosphoribose (cADPR)". Curr. Med. Chem. 11 (7): 847–55. doi:10.2174/0929867043455602. PMID 15078169.
^ Canales J, Fernández A, Rodrigues JR, Ferreira R, Ribeiro JM, Cabezas A, Costas MJ, Cameselle JC (2009). "Hydrolysis of the phosphoanhydride linkage of cyclic ADP-ribose by the Mn²⁺-dependent ADP-ribose/CDP-alcohol pyrophosphatase". FEBS Lett. 583 (10): 1593–8. doi:10.1016/j.febslet.2009.04.023. PMID 19379742.

External links

The web page of Dr. Hon Cheung Lee, the discoverer of cyclic ADP-ribose.
Cyclic ADP-ribose and NAADP. The first book on these two second messengers.

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 血小板生物学 platelet biology
2. ER／PR陰性、HER2陰性（トリプルネガティブ）乳癌の疫学、危険因子および臨床的アプローチ epidemiology risk factors and the clinical approach to er pr negative her2 negative triple negative breast cancer
3. 進行性前立腺癌の治療に対する実験的アプローチ investigational approaches for the treatment of advanced prostate cancer
4. 糖尿病性多発性神経障害の病因および予防 pathogenesis and prevention of diabetic polyneuropathy
5. 心筋における興奮収縮連関 excitation contraction coupling in myocardium

English Journal

'Click cyclic ADP-ribose': a neutral second messenger mimic.

Swarbrick JM1, Graeff R, Garnham C, Thomas MP, Galione A, Potter BV.Author information 1Wolfson Laboratory of Medicinal Chemistry, Dept. of Pharmacy and Pharmacology, University of Bath, Bath, BA2 7AY, UK. B.V.L.Potter@bath.ac.uk.AbstractAnalogues of the potent Ca(2+) releasing second messenger cyclic ADP-ribose (cADPR) with a 1,2,3-triazole pyrophosphate bioisostere were synthesised by click-mediated macrocyclisation. The ability to activate Ca(2+) release was surprisingly retained, and hydrolysis of cADPR by CD38 could also be inhibited, illustrating the potential of this approach to design drug-like signalling pathway modulators.
Chemical communications (Cambridge, England).Chem Commun (Camb).2014 Mar 7;50(19):2458-61. doi: 10.1039/c3cc49249d. Epub 2014 Jan 23.
Analogues of the potent Ca(2+) releasing second messenger cyclic ADP-ribose (cADPR) with a 1,2,3-triazole pyrophosphate bioisostere were synthesised by click-mediated macrocyclisation. The ability to activate Ca(2+) release was surprisingly retained, and hydrolysis of cADPR by CD38 could also be inh
PMID 24452494

Inflammation, caveolae and CD38-mediated calcium regulation in human airway smooth muscle.

Sathish V1, Thompson MA2, Sinha S2, Sieck GC3, Prakash YS1, Pabelick CM4.Author information 1Departments of Anesthesiology, Mayo Clinic, Rochester, MN 55905, USA; Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA.2Departments of Anesthesiology, Mayo Clinic, Rochester, MN 55905, USA.3Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA; Departments of Anesthesiology, Mayo Clinic, Rochester, MN 55905, USA.4Departments of Anesthesiology, Mayo Clinic, Rochester, MN 55905, USA; Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: pabelick.christina@mayo.edu.AbstractThe pro-inflammatory cytokine tumor necrosis factor-alpha (TNFα) increases expression of CD38 (a membrane-associated bifunctional enzyme regulating cyclic ADP ribose), and enhances agonist-induced intracellular Ca(2+) ([Ca(2+)]i) responses in human airway smooth muscle (ASM). We previously demonstrated that caveolae and their constituent protein caveolin-1 are important for ASM [Ca(2+)]i regulation, which is further enhanced by TNFα. Whether caveolae and CD38 are functionally linked in mediating TNFα effects is unknown. In this regard, whether the related cavin proteins (cavin-1 and -3) that maintain structure and function of caveolae play a role is also not known. In the present study, we hypothesized that TNFα effects on CD38 expression and function in human ASM involve caveolae. Caveolar fractions from isolated human ASM cells expressed CD38 and its expression was upregulated by exposure to 20ng/ml TNFα (48h). ASM cells expressed cavin-1 and cavin-3, which were also upregulated by TNFα. Knockdown of caveolin-1, cavin-1 or cavin-3 (using siRNA) all significantly reduced CD38 expression and ADP-ribosyl cyclase activity in the presence or absence of TNFα. Furthermore, caveolin-1, cavin-1 and cavin-3 siRNAs reduced [Ca(2+)]i responses to histamine under control conditions, and blunted the enhanced [Ca(2+)]i responses in TNFα-exposed cells. These data demonstrate that CD38 is expressed within caveolae and its function is linked to the caveolar regulatory proteins caveolin-1, cavin-1 and -3. The link between caveolae and CD38 is further enhanced during airway inflammation demonstrating the important role of caveolae in regulation of [Ca(2+)]i and contractility in the airway.
Biochimica et biophysica acta.Biochim Biophys Acta.2014 Feb;1843(2):346-51. doi: 10.1016/j.bbamcr.2013.11.011. Epub 2013 Nov 22.
The pro-inflammatory cytokine tumor necrosis factor-alpha (TNFα) increases expression of CD38 (a membrane-associated bifunctional enzyme regulating cyclic ADP ribose), and enhances agonist-induced intracellular Ca(2+) ([Ca(2+)]i) responses in human airway smooth muscle (ASM). We previously demonstr
PMID 24275509

Cancer stem cells display extremely large evolvability: alternating plastic and rigid networks as a potential Mechanism: Network models, novel therapeutic target strategies, and the contributions of hypoxia, inflammation and cellular senescence.

Csermely P1, Hódsági J2, Korcsmáros T3, Módos D4, Perez-Lopez AR2, Szalay K2, Veres DV2, Lenti K5, Wu LY6, Zhang XS6.Author information 1Department of Medical Chemistry, Semmelweis University, P.O. Box 260, H-1444 Budapest 8, Hungary. Electronic address: Csermely@med.semmelweis-univ.hu.2Department of Medical Chemistry, Semmelweis University, P.O. Box 260, H-1444 Budapest 8, Hungary.3Department of Genetics, Eötvös Loránd University, Pázmány P. s. 1C, H-1117 Budapest, Hungary.4Department of Genetics, Eötvös Loránd University, Pázmány P. s. 1C, H-1117 Budapest, Hungary; Semmelweis University, Department of Morphology and Physiology, Faculty of Health Sciences, Vas u. 17, H-1088 Budapest, Hungary.5Semmelweis University, Department of Morphology and Physiology, Faculty of Health Sciences, Vas u. 17, H-1088 Budapest, Hungary.6Institute of Applied Mathematics, Academy of Mathematics and Systems Science, Chinese Academy of Sciences, No. 55, Zhongguancun East Road, Beijing 100190, China.AbstractCancer is increasingly perceived as a systems-level, network phenomenon. The major trend of malignant transformation can be described as a two-phase process, where an initial increase of network plasticity is followed by a decrease of plasticity at late stages of tumor development. The fluctuating intensity of stress factors, like hypoxia, inflammation and the either cooperative or hostile interactions of tumor inter-cellular networks, all increase the adaptation potential of cancer cells. This may lead to the bypass of cellular senescence, and to the development of cancer stem cells. We propose that the central tenet of cancer stem cell definition lies exactly in the indefinability of cancer stem cells. Actual properties of cancer stem cells depend on the individual "stress-history" of the given tumor. Cancer stem cells are characterized by an extremely large evolvability (i.e. a capacity to generate heritable phenotypic variation), which corresponds well with the defining hallmarks of cancer stem cells: the possession of the capacity to self-renew and to repeatedly re-build the heterogeneous lineages of cancer cells that comprise a tumor in new environments. Cancer stem cells represent a cell population, which is adapted to adapt. We argue that the high evolvability of cancer stem cells is helped by their repeated transitions between plastic (proliferative, symmetrically dividing) and rigid (quiescent, asymmetrically dividing, often more invasive) phenotypes having plastic and rigid networks. Thus, cancer stem cells reverse and replay cancer development multiple times. We describe network models potentially explaining cancer stem cell-like behavior. Finally, we propose novel strategies including combination therapies and multi-target drugs to overcome the Nietzschean dilemma of cancer stem cell targeting: "what does not kill me makes me stronger".
Seminars in cancer biology.Semin Cancer Biol.2014 Jan 8. pii: S1044-579X(13)00130-2. doi: 10.1016/j.semcancer.2013.12.004. [Epub ahead of print]
Cancer is increasingly perceived as a systems-level, network phenomenon. The major trend of malignant transformation can be described as a two-phase process, where an initial increase of network plasticity is followed by a decrease of plasticity at late stages of tumor development. The fluctuating i
PMID 24412105

Japanese Journal

CD38 and its role in oxytocin secretion and social behavior

Higashida Haruhiro,Yokoyama Shigeru,Kikuchi Mitsuru,Munesue Toshio
Hormones and Behavior 61(3), 351-358, 2012-03
… Here, we review the functional roles of cyclic ADP-ribose and CD38, a transmembrane protein with ADP-ribosyl cyclase activity, in mouse social behavior via the regulation of oxytocin (OXT) release, an essential component of social cognition. …
NAID 120003959468

カルシウム動員セカンドメッセンジャー・サイクリックADPリボースの脳機能における役割

橋井美奈子
金沢大学十全医学会雑誌 = Journal of the J◆U00FB◆zen Medical Society 120(4), 171-176, 2011-12-01
NAID 10030163961

Oxytocin-induced elevation of ADP-ribosyl cyclase activity, cyclic ADP-riboseor Ca2+ concentrations is involved in autoregulation of oxytocin secretionin the hypothalamus and posterior pituitary in male mice

Lopatina Olga,Liu Hong-Xiang,Amina Sarwat,Hashii Minako,Higashida Haruhiro
Neuropharmacology 58(1), 50-55, 2010-01
… Therefore, it is interesting to investigate whether ADP-ribosyl cyclase-dependent signaling is involved in OT-induced OT release for social recognition in males, independent from female reproduction, and to determine its molecular mechanism. …
NAID 120001451026

Related Pictures

★リンクテーブル★

リンク元	「cADPR」「cyclic ADPR」「サイクリックADPリボース」
拡張検索	「cyclic ADP-ribose hydrolase」
関連記事	「cyclic」「ADP」「A」「AD」「ribose」

「cADPR」

Cyclic ADP-ribose
Identifiers
CAS Number	119340-53-3
ChEBI	CHEBI:31445
ChemSpider	21403087
IUPHAR/BPS	2445
Jmol interactive 3D	Image
MeSH	Cyclic+ADP-Ribose
PubChem	123847
	InChI InChI=1S/C15H21N5O13P2/c16-12-7-13-18-4-19(12)14-10(23)8(21)5(31-14)1-29-34(25,26)33-35(27,28)30-2-6-9(22)11(24)15(32-6)20(13)3-17-7/h3-6,8-11,14-16,21-24H,1-2H2,(H,25,26)(H,27,28)/t5-,6-,8-,9-,10-,11-,14-,15-/m1/s1 Key: BQOHYSXSASDCEA-KEOHHSTQSA-N ; InChI=1/C15H21N5O13P2/c16-12-7-13-18-4-19(12)14-10(23)8(21)5(31-14)1-29-34(25,26)33-35(27,28)30-2-6-9(22)11(24)15(32-6)20(13)3-17-7/h3-6,8-11,14-16,21-24H,1-2H2,(H,25,26)(H,27,28)/t5-,6-,8-,9-,10-,11-,14-,15-/m1/s1 Key: BQOHYSXSASDCEA-KEOHHSTQBN ;
	SMILES O[C@H]5[C@@H](O)[C@H]2O[C@@H]5COP(O)(=O)OP(O)(=O)OC[C@H]4O[C@@H](N3\C=N/c1c(ncn12)C3=N)[C@H](O)[C@@H]4O ;
Properties
Chemical formula	C15H21N5O13P2
Molar mass	541.301
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
	verify (what is ?)
	Infobox references

　　[★]

サイクリックADPリボース

関: cyclic ADP-ribose、cyclic ADPR

「cyclic ADPR」

　　[★]

サイクリックADPリボース

関: cADPR、cyclic ADP-ribose

「サイクリックADPリボース」

　　[★]

英: cyclic ADP-ribose、cyclic ADPR、cADPR

「cyclic ADP-ribose hydrolase」

　　[★]

サイクリックADPリボースヒドロラーゼ

関: ADP-ribosyl cyclase、ADPR cyclase、cADPR hydrolase

「cyclic」

　　[★]

adj.

環状の、環式の、周期性の、サイクリック

関: annular、circular、cyclical、cyclicity、cyclo、periodic、periodicity

「ADP」

　　[★]

アデノシン二リン酸 adenosine diphosphate adenosine 5'-diphosphate
5-aminolevulinic acid dehydratase porphyria
母指内転筋 adductor pollicis

「A」

　　[★]

「AD」

　　[★]

「ribose」

　　[★]

リボース

関: D-ribose

[1] Lee HC, Walseth TF, Bratt GT, Hayes RN, Clapper DL (1989). "Structural determination of a cyclic metabolite of NAD⁺ with intracellular Ca²⁺-mobilizing activity". J. Biol. Chem. 264 (3): 1608–15. PMID 2912976.

[2] Lee HC, Aarhus R, Levitt D (1994). "The crystal structure of cyclic ADP-ribose". Nat. Struct. Biol. 1 (3): 143–4. doi:10.1038/nsb0394-143. PMID 7656029.

[3] Guse AH (2004). "Regulation of calcium signaling by the second messenger cyclic adenosine diphosphoribose (cADPR)". Curr. Mol. Med. 4 (3): 239–48. doi:10.2174/1566524043360771. PMID 15101682.

[4] Lukyanenko V, Györke I, Wiesner TF, Györke S. 2001. Potentiation of Ca(2+) release by cADP-ribose in the heart is mediated by enhanced ER Ca2+ uptake into the sarcoplasmic reticulum. Circ Res. 89(7):614-22. PMID 11577027; 10.1161/hh1901.098066

[5] Prasad GS, McRee DE, Stura EA, Levitt DG, Lee HC, Stout CD (1996). "Crystal structure of Aplysia ADP-ribosyl cyclase, a homolog of the bifunctional ectozyme CD38". Nat. Struct. Biol. 3 (11): 957–64. doi:10.1038/nsb1196-957. PMID 8901875.

[6] Liu Q, Kriksunov IA, Graeff R, Munshi C, Lee HC, Hao Q (2005). "Crystal structure of the human CD38 extracellular domain". Structure 13 (9): 1331–9. doi:10.1016/j.str.2005.05.012. PMID 16154090.

[7] Guse AH (2004). "Biochemistry, biology, and pharmacology of cyclic adenosine diphosphoribose (cADPR)". Curr. Med. Chem. 11 (7): 847–55. doi:10.2174/0929867043455602. PMID 15078169.

[8] Canales J, Fernández A, Rodrigues JR, Ferreira R, Ribeiro JM, Cabezas A, Costas MJ, Cameselle JC (2009). "Hydrolysis of the phosphoanhydride linkage of cyclic ADP-ribose by the Mn²⁺-dependent ADP-ribose/CDP-alcohol pyrophosphatase". FEBS Lett. 583 (10): 1593–8. doi:10.1016/j.febslet.2009.04.023. PMID 19379742.

匿名

検索

案内

案内

cyclic ADP-ribose