Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) and Ca<sup>2+</sup>Mobilization

Mándi, Miklós; Bak, Judit

doi:10.1080/10799890802084085

Cited by 10 publications

(8 citation statements)

References 111 publications

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“…Significantly, NAADP‐induced Ca 2+ release appears to serve as a trigger for Ca 2+ release from IP 3 R and RYR and may also act to load Ca 2+ into the sarco‐endoplasmic reticulum. In addition, it has been reported that in pancreatic acinar cells NAADP can release Ca 2+ directly from RYR and ER so its primary effects may not be restricted to releasing Ca 2+ from lysosomes [25,114–116]. Secretory granules contain m m amounts of Ca 2+ although estimates of the free [Ca 2+ ] are considerably lower ranging from 10 to 40 μ m and 100 to 200 μ m depending upon the type of granule [47].…”

Section: Secretory Granules Acidic Organelles and Other Compartmentsmentioning

confidence: 99%

Compartmentalized signalling: Ca²⁺ compartments, microdomains and the many facets of Ca²⁺ signalling

Laude¹,

Simpson²

2009

The FEBS Journal

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Ca2+ regulates a multitude of cellular processes and does so by partitioning its actions in space and time. In this review, we discuss how Ca2+ responses are constructed from small quantal (elementary) events that have the potential to propagate to produce large pan‐cellular responses. We review how Ca2+ is compartmentalized both physically and functionally, and describe how each organelle has its own distinct Ca2+‐handling properties. We explain how coordination of the movement of Ca2+ between organelles is used to shape and hone Ca2+ signals. Finally, we provide a number of specific examples of where compartmentation and localization of Ca2+ are crucial to cell function.

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Section: Secretory Granules Acidic Organelles and Other Compartmentsmentioning

confidence: 99%

Compartmentalized signalling: Ca²⁺ compartments, microdomains and the many facets of Ca²⁺ signalling

Laude¹,

Simpson²

2009

The FEBS Journal

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“…1). Furthermore, besides protein modification, NAD + may be also used for the synthesis of signaling molecules, including ADPribose (ADPR) [11][12][13], cyclic ADP-ribose (cADPR) [14,15], nicotinic acid adenine dinucleotide phosphate (NAADP) [16,17], and 2'-phospho-cyclic ADP-ribose (P-cADPR) [18,19], all important in Ca 2 + signaling ( Fig. 1).…”

Section: Niacin Functionsmentioning

confidence: 99%

NAD in Skin: Therapeutic Approaches for Niacin

Benavente

Jacobson²,

Jacobson³

2009

CPD

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The maintenance and regulation of cellular NAD(P)(H) content and its influence on cell function involves many metabolic pathways, some of which remain poorly understood. Niacin deficiency in humans, which leads to low NAD status, causes sun sensitivity in skin, indicative of deficiencies in responding to UV damage. Animal models of niacin deficiency demonstrate genomic instability and increased cancer development in sensitive tissues including skin. Cell culture models of niacin deficiency have allowed the identification of NAD-dependent signaling events critical in early skin carcinogenesis. Niacin restriction in immortalized keratinocytes leads to an increased expression and activity of NADPH oxidase resulting in an accumulation of ROS, providing a potential survival mechanism as has been shown to occur in cancer cells. Niacin deficient keratinocytes are more sensitive to photodamage, as both poly(ADP-ribose) polymerases and Sirtuins are inhibited by the unavailability of their substrate, NAD+, leading to unrepaired DNA damage upon photodamage and a subsequent increase in cell death. Furthermore, the identification of the nicotinic acid receptor in human skin keratinocytes provides a further link to niacin's role as a potential skin cancer prevention agent and suggests the nicotinic acid receptor as a potential target for skin cancer prevention agents. The new roles for niacin as a modulator of differentiation and photo-immune suppression and niacin status as a critical resistance factor for UV damaged skin cells are reviewed here.

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“…Related to the relatively higher cysteine content (9 cysteines versus 3 or 4 of the other two human isoforms), the protein is very prone to oxidation, which can be prevented by thiol protecting agents [105]. Interestingly, Cys 164 and Cys 165 form a distinctive structural pair within NMNAT family [106]. The 3D structure of NMNAT2 has yet to be determined.…”

Section: Human Nmn/namn Adenylyltransferasementioning

confidence: 97%

“…Furthermore, NADP is both an important intermediate for cellular defense against oxidative stress [161], and a substrate for NaADP formation by NAD glycohydrolase/ADP ribosyl cyclase, which catalyzes a pyridine base exchange reaction [162,163]. NaADP is recognized as one of the most powerful activators of intracellular Ca 2+ signaling [162,164,165]. Given that NAD and NADP play such different physiological roles, it is conceivable that their cellular levels are finely regulated, and thus that the NADK-catalyzed reaction is a key regulation point for a large number of cellular processes.…”

Section: Nad Kinase (Nadk)mentioning

confidence: 99%

NAD(P) Biosynthesis Enzymes as Potential Targets for Selective Drug Design

Magni

Stefano²,

Orsomando

et al. 2009

CMC

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NAD(P) biosynthetic pathways can be considered a generous source of enzymatic targets for drug development. Key reactions for NAD(P) biosynthesis in all organisms, common to both de novo and salvage routes, are catalyzed by NMN/NaMN adenylyltransferase (NMNAT), NAD synthetase (NADS), and NAD kinase (NADK). These reactions represent a three-step pathway, present in the vast majority of living organisms, which is responsible for the generation of both NAD and NADP cellular pools. The validation of these enzymes as drug targets is based on their essentiality and conservation among a large variety of pathogenic microorganisms, as well as on their differential structural features or their differential metabolic contribution to NAD(P) homeostasis between microbial and human cell types. This review describes the structural and functional properties of eubacterial and human enzymes endowed with NMNAT, NADS, and NADK activities, as well as with nicotinamide phosphoribosyltransferase (NamPRT) and nicotinamide riboside kinase (NRK) activities, highlighting the species-related differences, with emphasis on their relevance for drug design. In addition, since the overall NMNAT activity in humans is accounted by multiple isozymes differentially involved in the metabolic activation of antineoplastic compounds, their individual diagnostic value for early therapy optimization is outlined. The involvement of human NMNAT in neurodegenerative disorders and its role in neuroprotection is also discussed.

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Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) and Ca²⁺Mobilization

Cited by 10 publications

References 111 publications

Compartmentalized signalling: Ca²⁺ compartments, microdomains and the many facets of Ca²⁺ signalling

Compartmentalized signalling: Ca²⁺ compartments, microdomains and the many facets of Ca²⁺ signalling

NAD in Skin: Therapeutic Approaches for Niacin

NAD(P) Biosynthesis Enzymes as Potential Targets for Selective Drug Design

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Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) and Ca2+Mobilization

Cited by 10 publications

References 111 publications

Compartmentalized signalling: Ca2+ compartments, microdomains and the many facets of Ca2+ signalling

Compartmentalized signalling: Ca2+ compartments, microdomains and the many facets of Ca2+ signalling

NAD in Skin: Therapeutic Approaches for Niacin

NAD(P) Biosynthesis Enzymes as Potential Targets for Selective Drug Design

Contact Info

Product

Resources

About

Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) and Ca²⁺Mobilization

Compartmentalized signalling: Ca²⁺ compartments, microdomains and the many facets of Ca²⁺ signalling

Compartmentalized signalling: Ca²⁺ compartments, microdomains and the many facets of Ca²⁺ signalling