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2012国际生理学学术大会

作者： Yuming Li Haitao Li Yanzhi Zhao Yanqiu Cui Junya Wang Dongmei Zhang Zhongqiu Li Department of Physiology and Pathophysiology Capital Medical University Yanjing Medical College

FKBP12.6 and cadpR are two regulators of ryanodine Ca release receptors which play a pivotal role in the regulation of numerous cellular *** current study was designed to examine the effect of FKBP12.6 and adp-ribosyl cyclase(adpRclase,a key regulator of endogenous cadpR production) on the function of *** this study,both FKBP12.6 knockout and wild 129 mice(8-12 week old) were divided into three groups respectively:control group,mice were given a 7 day continuous infusion of 0.9%NaCl;DHAB group,mice were given a 7 day continuous infusion of 2,2’-dihydroxyazobenzene(DHAB,a adpRclase inhibitor,2 mg/***);cadpR group,mice were given a 7 day continuous infusion of exogenous cadpR(1 mg/***) *** the 7th day,abilities of learning and memory of the mice were tested by using the Morris water maze and space *** expression ofadpRclase mRNA and protein in hippocampus of mice were detected by using RT-PCR and Western Blotting *** Morris water maze and space experiments revealed that the abilities of learning and memory were decreased significantly in FKBP 12.6 knockout mice and DHAB treated wild 129 *** abilities decrease was aggravated by DHAB and alleviated by exogenous cadpR in FKBP12.6 knockout *** of mRNA and protein of adpRclase was lower in FKBP12.6 knockout mice than that in wild *** inhibited the expression of adpRclase in both FKBP12.6 knockout and wild *** data shows that adpRclase expression was decreased by FKBP12.6 knockout and FKBP 12.6/adpRclase/cadpR may maintain the function of hippocampus in mice.

关键词： FKBP12.6 adp-ribosyl cyclase hippocampus

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Cyclic adp-ribose and NAadp:fraternal twin messengers for calcium signaling

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Science China(Life Sciences) 2011年第8期54卷 699-711页

作者： Hon Cheung LEE Department of Physiology University of Hong Kong

The concept advanced by Berridge and colleagues that intracellular Ca2+-stores can be mobilized in an agonist-dependent and messenger(IP3)-mediated manner has put Ca 2+-mobilization at the center stage of signal transduction *** the late 1980s,we showed that Ca2+-stores can be mobilized by two other messengers unrelated to inositol trisphosphate(IP 3) and identified them as cyclic adp-ribose(cadpR),a novel cyclic nucleotide from NAD,and nicotinic acid adenine dinucleotide phosphate(NAadp),a linear metabolite of *** messenger functions have now been documented in a wide range of systems spanning three biological *** evidence indicates that the target of cadpR is the ryanodine receptor in the sarco/endoplasmic reticulum,while that of NAadp is the two pore channel in endolysosomes. As cadpR and NAadp are structurally and functionally distinct,it is remarkable that they are synthesized by the same *** are thus fraternal twin *** first identified the Aplysia adp-ribosyl cyclase as one such enzyme and,through homology,found its mammalian homolog,*** knockout in mice confirms the important roles of CD38 in diverse physiological functions from insulin secretion,susceptibility to bacterial infection,to social behavior of mice through modulating neuronal oxytocin *** have elucidated the catalytic mechanisms of the Aplysia cyclase and CD38 to atomic resolution by crystallography and site-directed *** article gives a historical account of the cadpR/NAadp/CD38-signaling pathway and describes current efforts in elucidating the structure and function of its components.

关键词： cyclic adp-ribose cadpR NAadp nicotinic acid adenine dinucleotide phosphate CD38 adp-ribosyl cyclase Calcium mobilization and signaling

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