Determination of cyclic guanosine- and cyclic adenosine monophosphate (cGMP and cAMP) in human plasma and animal tissues by solid phase extraction on silica and liquid chromatography–triple quadrupole mass spectrometry

Damme, Thomas Van; Zhang, Yanhua; Lynen, Frédéric; Sandra, Patrick

doi:10.1016/j.jchromb.2012.10.002

Cited by 34 publications

(21 citation statements)

References 45 publications

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“…The lower limit of quantification (LOQ) was set according to internationally well-accepted criteria (the lowest concentration of the calibration range with precision and accuracy <20%) and was 0.15 nM for cGMP and 0.26 nM for cAMP. These LOQ values are lower than those published for similar methods [20,21] and allow the analysis of samples with very low concentrations of the analytes. Taking into account cAMP and cGMP basal levels in healthy people, in the range of 8-14 nM (cAMP) and 2-5 nM (cGMP) [8], any improvement in LOQ values is a remarkable achievement for the aim of this project.…”

Section: Lc-ms/ms Methods Validationmentioning

confidence: 57%

Decreased levels of guanosine 3′, 5′‐monophosphate (cGMP) in cerebrospinal fluid (CSF) are associated with cognitive decline and amyloid pathology in Alzheimer's disease

Ugarte

Gil-Bea

García‐Barroso

et al. 2015

Neuropathology Appl Neurobio

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Section: Lc-ms/ms Methods Validationmentioning

confidence: 57%

Decreased levels of guanosine 3′, 5′‐monophosphate (cGMP) in cerebrospinal fluid (CSF) are associated with cognitive decline and amyloid pathology in Alzheimer's disease

Ugarte

Gil-Bea

García‐Barroso

et al. 2015

Neuropathology Appl Neurobio

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“…The production of 29,39-cAMP as well as other nucleoside 29,39-cyclic monophosphates by living tissues has been corroborated by multiple independent laboratories. [26][27][28][29][30][31] Our hypothesis that injury increases 29,39-cAMP production also has received confirmation. For example, brain trauma in mice increases brain interstitial levels of 29,39-cAMP, and 29,39-cAMP is elevated in cerebrospinal fluid of humans in the early hours after traumatic brain injury.…”

Section: Discussionmentioning

confidence: 83%

Renal 2′,3′-Cyclic Nucleotide 3′-Phosphodiesterase Is an Important Determinant of AKI Severity after Ischemia-Reperfusion

Jackson

Menshikova

et al. 2015

JASN

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A positional isomer of 39,59-cAMP, 29,39-cAMP, is produced by kidneys in response to energy depletion, and renal 29,39-cyclic nucleotide 39-phosphodiesterase (CNPase) metabolizes 29,39-cAMP to 29-AMP; 29,39-cAMP is a potent opener of mitochondrial permeability transition pores (mPTPs), which can stimulate autophagy. Because autophagy protects against AKI, it is conceivable that inhibition of CNPase protects against ischemia-reperfusion (IR) -induced AKI. Therefore, we investigated renal outcomes, mitochondrial function, number, area, and autophagy in CNPase-knockout (CNPase 2/2 ) versus wild-type (WT) mice using a unique two-kidney, hanging-weight model of renal bilateral IR (20 minutes of ischemia followed by 48 hours of reperfusion). Analysis of urinary purines showed attenuated metabolism of 29,39-cAMP to 29-AMP in CNPase 2/2 mice. Neither genotype nor IR affected BP, heart rate, urine volume, or albumin excretion. In WT mice, renal IR reduced 14 C-inulin clearance (index of GFR) and increased renal vascular resistance (measured by transit time nanoprobes) and urinary excretion of kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin. IR did not affect these parameters in CNPase 2/2 mice. Histologic analysis revealed that IR induced severe damage in kidneys from WT mice, whereas histologic changes were minimal after IR in CNPase 2/2 mice. Measurements of renal cardiolipin levels, citrate synthase activity, rotenone-sensitive NADH oxidase activity, and proximal tubular mitochondrial and autophagosome area and number (by transmission electron microscopy) indicted accelerated autophagy/ mitophagy in injured CNPase 2/2 mice. We conclude that CNPase deletion attenuates IR-induced AKI, in part by accelerating autophagy with targeted removal of damaged mitochondria. In response to energy depletion, rat 1,2 and mouse 3 kidneys produce 29,39-cAMP, a positional isomer of 39,59-cAMP that is generated when mRNA is enzymatically degraded. 2 A study by Azarashvili et al. 4 shows that 29,39-cAMP is a potent opener of mitochondrial permeability transition pores (mPTPs).Opening of mPTPs causes mitochondria damage, 5 and mitochondrial damage is a stimulus for autophagy. [6][7][8] Renal autophagy protects against AKI, [9][10][11][12][13][14][15][16] and insufficient autophagy contributes to organ failure. 17 Therefore, it is conceivable that 29,39-cAMP, by increasing autophagy, protects against AKI. Our recent studies identify 29,39-cyclic nucleotide 39-phosphodiesterase (CNPase) as an important enzyme mediating the renal metabolism of

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“…Because the intracellular level of the cAMP second messenger could not be measured by antibody-based assays due to cross-reactivity with c-di-AMP or cGAMP (G. Lebon, personal communication), this dosage was performed by liquid chromatography-mass spectrometry (LC-MS) (14), with modifications for MS n selected multi-ion analysis. Briefly, purified monocytes (95% CD14 ϩ cells) were cultured (5 million/well) with or without c-di-AMP (5 M) for 16 h in complete medium supplemented with 3-isobutyl-1-methylxanthine (IBMX) (45 M) and then collected, washed, and extracted with acetonitrile-methanol-water (40:40:20, vol/vol/vol).…”

Section: Myeloid and Cd34mentioning

confidence: 99%

Human Monocyte Recognition of Adenosine-Based Cyclic Dinucleotides Unveils the A2a G_αsProtein-Coupled Receptor Tonic Inhibition of Mitochondrially Induced Cell Death

Tosolini

Pont

Bétous

et al. 2015

Molecular and Cellular Biology

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Cyclic dinucleotides are important messengers for bacteria and protozoa and are well-characterized immunity alarmins for infected mammalian cells through intracellular binding to STING receptors. We sought to investigate their unknown extracellular effects by adding cyclic dinucleotides to the culture medium of freshly isolated human blood cells in vitro. Here we report that adenosine-containing cyclic dinucleotides induce the selective apoptosis of monocytes through a novel apoptotic pathway. We demonstrate that these compounds are inverse agonist ligands of A2a, a G ␣s -coupled adenosine receptor selectively expressed by monocytes. Inhibition of monocyte A2a by these ligands induces apoptosis through a mechanism independent of that of the STING receptors. The blockade of basal (adenosine-free) signaling from A2a inhibits protein kinase A (PKA) activity, thereby recruiting cytosolic p53, which opens the mitochondrial permeability transition pore and impairs mitochondrial respiration, resulting in apoptosis. A2a antagonists and inverse agonist ligands induce apoptosis of human monocytes, while A2a agonists are antiapoptotic. In vivo, we used a mock developing human hematopoietic system through NSG mice transplanted with human CD34؉ cells. Treatment with cyclic di-AMP selectively depleted A2a-expressing monocytes and their precursors via apoptosis. Thus, monocyte recognition of cyclic dinucleotides unravels a novel proapoptotic pathway: the A2a G ␣s protein-coupled receptor (GPCR)-driven tonic inhibitory signaling of mitochondrion-induced cell death. P urine and pyrimidine-based signaling is a fundamental and conserved mode of intercellular communication. In the body, mononucleotides are the major mediators of tissue protection and regeneration, for example, adenosine, which is released from damaged cells. In contrast, microorganisms use cyclic dinucleotides, such as cyclic di-AMP (c-di-AMP) and cyclic di-GMP (cdi-GMP), which are secreted by bacteria and protozoa, respectively (1, 2). As a defense mechanism, mammalian cells have evolved a means to sense cyclic dinucleotides. When infected with retroviruses (3) or carrying cytosolic DNA (4), cells assemble an endogenous 2=,3= cyclic GMP-AMP (cGAMP) dinucleotide which is recognized by the intracellular protein STING to induce type I interferon (IFN) responses (5). In this way, intracellular cyclic dinucleotides represent important alarmins in immunity.Extracellular cyclic dinucleotides are released from infected dying cells or damaged tissues and also represent important signals, but whether and how mammalian cells can detect these and respond is presently unknown. We hypothesized that human peripheral blood cells might be capable of detecting extracellular cyclic dinucleotides. We found that the extracellular 3=,5= cyclic dinucleotides c-di-AMP and cGAMP are specifically recognized by human monocytes expressing the A2a adenosine receptor and can selectively induce their apoptosis. Analysis of the role of A2a in this apoptotic response showed that it controls the s...

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Determination of cyclic guanosine- and cyclic adenosine monophosphate (cGMP and cAMP) in human plasma and animal tissues by solid phase extraction on silica and liquid chromatography–triple quadrupole mass spectrometry

Cited by 34 publications

References 45 publications

Decreased levels of guanosine 3′, 5′‐monophosphate (cGMP) in cerebrospinal fluid (CSF) are associated with cognitive decline and amyloid pathology in Alzheimer's disease

Decreased levels of guanosine 3′, 5′‐monophosphate (cGMP) in cerebrospinal fluid (CSF) are associated with cognitive decline and amyloid pathology in Alzheimer's disease

Renal 2′,3′-Cyclic Nucleotide 3′-Phosphodiesterase Is an Important Determinant of AKI Severity after Ischemia-Reperfusion

Human Monocyte Recognition of Adenosine-Based Cyclic Dinucleotides Unveils the A2a G_αsProtein-Coupled Receptor Tonic Inhibition of Mitochondrially Induced Cell Death

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Determination of cyclic guanosine- and cyclic adenosine monophosphate (cGMP and cAMP) in human plasma and animal tissues by solid phase extraction on silica and liquid chromatography–triple quadrupole mass spectrometry

Cited by 34 publications

References 45 publications

Decreased levels of guanosine 3′, 5′‐monophosphate (cGMP) in cerebrospinal fluid (CSF) are associated with cognitive decline and amyloid pathology in Alzheimer's disease

Decreased levels of guanosine 3′, 5′‐monophosphate (cGMP) in cerebrospinal fluid (CSF) are associated with cognitive decline and amyloid pathology in Alzheimer's disease

Renal 2′,3′-Cyclic Nucleotide 3′-Phosphodiesterase Is an Important Determinant of AKI Severity after Ischemia-Reperfusion

Human Monocyte Recognition of Adenosine-Based Cyclic Dinucleotides Unveils the A2a GαsProtein-Coupled Receptor Tonic Inhibition of Mitochondrially Induced Cell Death

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Human Monocyte Recognition of Adenosine-Based Cyclic Dinucleotides Unveils the A2a G_αsProtein-Coupled Receptor Tonic Inhibition of Mitochondrially Induced Cell Death