Measurement of steroid synthesis in zona glomerulosa cells by liquid chromatography–electrospray ionization–mass spectrometry: inhibition by nitric oxide

Nithipatikom, Kasem; Holmes, Blythe B.; Isbell, Marilyn A.; Hanke, Craig J.; Gómez-Sánchez, Celso E.; Campbell, William B.

doi:10.1016/j.ab.2004.11.025

Cited by 13 publications

(8 citation statements)

References 28 publications

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“…To unambiguously demonstrate that adipocytes secrete aldosterone, high-performance liquid chromatography-mass-spectrometry studies were performed. Specific aldosterone mass transition (361.2-343.3) 23 was detected in the CCM from 3T3-L1 adipocytes ( Figure 1F) and in the mineralocorticoid-supplemented medium ( Figure 1G) with prominent peak eluted at 0.93 seconds. No aldosterone was detectable in control nonconditioned medium ( Figure 1H).…”

Section: Adipocytes Release Aldosteronementioning

confidence: 99%

Adipocytes Produce Aldosterone Through Calcineurin-Dependent Signaling Pathways

et al. 2012

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Abstract-We reported aldosterone as a novel adipocyte-derived factor that regulates vascular function. We aimed to investigate molecular mechanisms, signaling pathways, and functional significance of adipocyte-derived aldosterone and to test whether adipocyte-derived aldosterone is increased in diabetes mellitus-associated obesity, which contributes to vascular dysfunction. Studies were performed in the 3T3-L1 adipocyte cell line and mature adipocytes isolated from human and mouse (C57BL/6J) adipose tissue. Mesenteric arteries with and without perivascular fat and mature adipocytes were obtained from obese diabetic db/db and control db/ϩ mice. Aldosterone synthase (CYP11B2; mRNA and protein) was detected in 3T3-L1 and mature adipocytes, which secrete aldosterone basally and in response to angiotensin II (Ang II). In 3T3-L1 adipocytes, Ang II stimulation increased aldosterone secretion and CYP11B2 expression. Ang II effects were blunted by an Ang II type 1 receptor antagonist (candesartan) and inhibitors of calcineurin (cyclosporine A and FK506) and nuclear factor of activated T-cells (VIVIT). FAD286 (aldosterone synthase inhibitor) blunted adipocyte differentiation. In candesartan-treated db/db mice (1 mg/kg per day, 4 weeks) increased plasma aldosterone, CYP11B2 expression, and aldosterone secretion were reduced. Acetylcholine-induced relaxation in db/db mesenteric arteries containing perivascular fat was improved by eplerenone (mineralocorticoid receptor antagonist) without effect in db/ϩ mice. Adipocytes possess aldosterone synthase and produce aldosterone in an Ang II/Ang II type 1 receptor/calcineurin/nuclear factor of activated T-cells-dependent manner. Functionally adipocyte-derived aldosterone regulates adipocyte differentiation and vascular function in an autocrine and paracrine manner, respectively. These novel findings identify adipocytes as a putative link between aldosterone and vascular dysfunction in diabetes mellitus-associated obesity. (Hypertension. 2012;59:1069-1078.) • Online Data Supplement

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Section: Adipocytes Release Aldosteronementioning

confidence: 99%

Adipocytes Produce Aldosterone Through Calcineurin-Dependent Signaling Pathways

et al. 2012

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“…Our group previously showed that LPS was an important stimulator of MMP‐9 production in cultured glial cells as well as in the LPS‐induced neuroninflammation animal model (Mun‐Bryce and Rosenberg,1998a; Rosenberg et al,2001). DETA NONOate has been widely used as an NO‐releasing reagent to test the effect of NO in vitro studies, with a concentration range from 0.1 to 1 mM (Okamoto et al,2002; Akool et al,2003; Huerta‐Yepez et al,2004; Nithipatikom et al,2005; Wang and MacNaughton,2005; Sinha et al,2006). In this study, we investigated the effect of NO on LPS‐induced MMP‐9 expression in primary cultured astrocytes by using DETA NONOate.…”

mentioning

confidence: 99%

AUF-1 mediates inhibition by nitric oxide of lipopolysaccharide-induced matrix metalloproteinase-9 expression in cultured astrocytes

2006

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Neuroinflammatory diseases are associated with increased production of matrix metalloproteinase-9 (MMP-9) and excessive generation of nitric oxide (NO). NO has been reported to have variable effects on MMP-9 gene expression and activation in various cell types. In the present study, we investigated the effect of NOon MMP-9 expression in primary cortical astrocytes. Zymography and real-time PCR showed that lipopolysaccharide (LPS) dramatically increased latent MMP-9 gelatinolytic activity and MMP-9 mRNA expression. By using the NO donor DETA NONOate, we observed a dose-dependent inhibition of MMP-9 induction by LPS. Active forms of MMP-9 were not found by zymography after NO treatment. The MEK1/2 inhibitor U0126 completely inhibited LPS-induced MMP-9, which was partially inhibited by the p38 MAPK inhibitor SB203580. NO had no effect on LPS-stimulated ERK1/2 and p38 MAPK activation, suggesting that the inhibitory action of NO occurs downstream of MAPK cascades. Real-time PCR analysis showed that NO accelerated the degradation of MMP-9 mRNA after LPS induction. Western blotting and pull-down assay demonstrated that NO increased AUF-1 expression as well as its specific binding to the MMP-9 gene 3'-untranslated region. Knockdown of AUF-1 with siRNA partially reversed the inhibitory action of NO on LPS-stimulated MMP-9 induction. We conclude that NO does not activate MMP-9 in astrocyte cultures but reduces LPS-induced MMP-9 expression via accelerating MMP-9 mRNA degradation, which is partially mediated by AUF-1. Our results suggest that elevated NO concentrations may suppress MMP-9 and restrict the inflammatory response in neurodegenerative diseases.

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“…It is generally believed that MS/MS is specific enough to distinguish compounds of interest from the interferences from the biological samples, so chromatography with partially overlapping peaks were often used [12,16,21,22]. However, we observed that interferences from the tissue sample matrix were significant when the substrate concentration was much higher than the product and that MS/MS alone was not sufficient to filter out these interferences.…”

Section: Introductionmentioning

confidence: 74%

“…These types of MS/MS signal interferences generated from isomeric cortisol compounds in biological samples when detecting cortisol have not been reported previously. In some of earlier LC/MS/MS studies, cortisol and cortisone were not completely separated in the HPLC [12,14,22,24]. It is therefore possible that the cortisol concentrations reported in some of the previous studies may have artificially augmented by the isomeric compounds.…”

Section: Isomeric Interferences In Quantitation Of Ex Vivo Samples (Lmentioning

confidence: 96%

Quantitative measurements of corticosteroids in ex vivo samples using on-line SPE-LC/MS/MS

Gao

Chiou

Camp

et al. 2009

Journal of Chromatography B

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Measurement of steroid synthesis in zona glomerulosa cells by liquid chromatography–electrospray ionization–mass spectrometry: inhibition by nitric oxide

Cited by 13 publications

References 28 publications

Adipocytes Produce Aldosterone Through Calcineurin-Dependent Signaling Pathways

Adipocytes Produce Aldosterone Through Calcineurin-Dependent Signaling Pathways

AUF-1 mediates inhibition by nitric oxide of lipopolysaccharide-induced matrix metalloproteinase-9 expression in cultured astrocytes

Quantitative measurements of corticosteroids in ex vivo samples using on-line SPE-LC/MS/MS

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