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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2006.1
- 수록면
- 718 - 726 (9page)
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초록· 키워드
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ADP-ribosyl cyclase (ADPR-cyclase) produces a
Ca2+-mobilizing second messenger, cyclic ADPribose
(cADPR), from β-NAD+. A prototype of mam -
malian ADPR-cyclases is a lymphocyte antigen
CD38. Accumulating evidence indicates that
ADPR-cyclases other than CD38 are expressed in
various cells and organs. In this study, we discovered
a small molecule inhibitor of kidney ADPR-cyclase.
This compound inhibited kidney ADPR-cyclase
activity but not CD38, spleen, heart or brain
ADPR-cyclase activity in vitro. Characterization of
the compound in a cell-based system revealed that
an extracellular calcium-sensing receptor (CaSR)-
mediated cADPR production and a later long-lasting
increase in intracellular Ca2+ concentration ([Ca2+]i)
in mouse mesangial cells were inhibited by the
pre-treatment with this compound. In contrast, the
compound did not block CD3/TCR-induced cADPR
production and the increase of [Ca2+]i in Jurkat T cells,
which express CD38 exclusively. The long-lasting
Ca2+ signal generated by both receptors was in -
hibited by pre-treatment with an antagonistic cADPR
derivative, 8-Br-cADPR, indicating that the Ca2+
signal is mediated by the ADPR-cyclse metabolite,
cADPR. Moreover, among structurally similar compounds
tested, the compound inhibited most
potently the cADPR production and Ca2+ signal
induced by CaSR. These findings provide evidence
for existence of a distinct ADPR-cyclase in the kidney
and basis for the development of tissue specific
inhibitors.
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등록된 정보가 없습니다.
참고문헌 (28)
참고문헌 신청
/ / ADP ribosyl cyclase activity of a novel bone marrow stromal cell surface molecule : 244 ~ 1 8
/ / Enzymatic synthesis and characterizations of cyclic GDP- ribose A procedure for distinguishing enzymes with ADP- ribosyl cyclase activity : 30260 ~ 7
/ / Synthesis and characterization of antagonists of cyclic-ADP-ribose-induced Carelease : 235 ~ 42
/ / an enzyme that cyclizes NAD+ into a calcium-mobilizing metabolite : 203 ~ 9
/ 1996 / Stimulation of ADP-ribosyl cyclase activity of the cel surface antigen CD38 by zinc ions resulting from inhibition of its NAD+ glycohydrolase activity 239 : 177 ~ 1
/ / Enzymatic synthesis and characterizations of cyclic GDP- ribose A procedure for distinguishing enzymes with ADP- ribosyl cyclase activity : 30260 ~ 7
/ / Synthesis and characterization of antagonists of cyclic-ADP-ribose-induced Carelease : 235 ~ 42
/ / an enzyme that cyclizes NAD+ into a calcium-mobilizing metabolite : 203 ~ 9
/ 1996 / Stimulation of ADP-ribosyl cyclase activity of the cel surface antigen CD38 by zinc ions resulting from inhibition of its NAD+ glycohydrolase activity 239 : 177 ~ 1
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