The role of lipid second messengers in aldosterone synthesis and secretion

Spaulding, Shinjini C; Bollag, Wendy B.

doi:10.1016/j.jlr.2022.100191

Cited by 15 publications

(9 citation statements)

References 123 publications

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“…They are abundant in the brain and highly expressed in myelin. The hydrolysis of sphingolipids can produce ceramide (Cer), ceramide-1-phosphate, sphingosine, and phosphorylated sphingosine S1P [ 28 ]. Dietary sphingolipids can also be hydrolyzed into ceramides and sphingosines for absorption [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Determination of endogenous sphingolipid content in stroke rats and HT22 cells subjected to oxygen-glucose deprivation by LC‒MS/MS

et al. 2023

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Background Stroke is the leading cause of death in humans worldwide, and its incidence increases every year. It is well documented that lipids are closely related to stroke. Analyzing the changes in lipid content in the stroke model after absolute quantification and investigating whether changes in lipid content can predict stroke severity provides a basis for the combination of clinical stroke and quantitative lipid indicators. Methods This paper establishes a rapid, sensitive, and reliable LC‒MS/MS analytical method for the detection of endogenous sphingolipids in rat serum and brain tissue and HT22 cells and quantifies the changes in sphingolipid content in the serum and brain tissue of rats from the normal and pMCAO groups and in cells from the normal and OGD/R groups. Using sphingosine (d17:1) as the internal standard, a chloroform: methanol (9:1) mixed system was used for protein precipitation and lipid extraction, followed by analysis by reversed-phase liquid chromatography coupled to triple quadrupole mass spectrometry. Results Based on absolute quantitative analysis of lipids in multiple biological samples, our results show that compared with those in the normal group, the contents of sphinganine (d16:0), sphinganine (d18:0), and phytosphingosine were significantly increased in the model group, except sphingosine-1-phosphate, which was decreased in various biological samples. The levels of each sphingolipid component in serum fluctuate with time. Conclusion This isotope-free and derivatization-free LC‒MS/MS method can achieve absolute quantification of sphingolipids in biological samples, which may also help identify lipid biomarkers of cerebral ischemia. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Determination of endogenous sphingolipid content in stroke rats and HT22 cells subjected to oxygen-glucose deprivation by LC‒MS/MS

et al. 2023

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“…In this manuscript, by integrating metabolomics data, we identified abnormal expression of metabolites in 5/6 Nx group, the metabolites with relative higher Recent report indicated that DAG was implicated in AngⅡ-modified production of aldosterone 58 . As a lipid second messenger, DAG exerted an influence on the production of aldosterone by regulating protein kinase C and calcium homeostasis 59 .…”

Section: Discussionmentioning

confidence: 99%

Nephrectomy and high-salt diet inducing pulmonary hypertension and kidney damage by increasing Ang II concentration in rats

Jiang,

Yang,

Zhang

et al. 2024

Preprint

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Background: Pulmonary hypertension (PH) is a common complication in patients with chronic kidney disease (CKD), affecting prognosis. However, the pathogenesis is not clear, and the lack of a stable animal model is a significant factor. Methods: In this study, a rat model of chronic kidney disease with pulmonary hypertension (CKD-PH) was developed through 5/6 nephrectomy combined with a high-salt diet. The model's hemodynamics and pathological changes in multiple organs were dynamically assessed. Lung tissues and serum were collected from the model rats to measure the expression of ACE2, the expression levels of vascular active components related to the renin-angiotensin-aldosterone system (RAAS), and changes in the serum metabolic profile of the model. Results: After 14 weeks post-surgery, the CKD-PH rat model exhibited significant changes in hemodynamic parameters indicative of pulmonary arterial hypertension, along with alterations such as right ventricular hypertrophy. However, no evidence of pulmonary vascular remodeling was observed. An imbalance in the renin-angiotensin-aldosterone system was identified in the CKD-PH rat models. Downregulation of ACE2 expression was observed in pulmonary tissues. The serum metabolic profile of the CKD-PH rat models showed distinct differences compared to the sham surgery group. Conclusions: The development of pulmonary arterial hypertension in CKD-PH rats may be primarily attributed to the disruption of the renin-angiotensin-aldosterone system (RAAS), coupled with a decrease in ACE2 expression in pulmonary vascular endothelial tissues and metabolic disturbances.

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“…The sphingolipid signaling pathway, one of the most crucial secondary signaling systems within cells [ 101 ], stimulates specific sphingosine kinases to generate sphingosine-1-phosphate (S1P), a key molecule in the sphingolipid signaling pathway [ 102 ]. Inflammatory stimuli can accelerate the production of sphingolipids, resulting in sphingolipase-induced production of ceramide (Cer) and sphingosine.…”

Section: Discussionmentioning

confidence: 99%

Unraveling the Mechanism of Xiaochaihu Granules in Alleviating Yeast-Induced Fever Based on Network Analysis and Experimental Validation

Chen,

Wu,

et al. 2024

Pharmaceuticals

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Xiaochaihu granules (XCHG) are extensively used to treat fever. Nevertheless, the underlying mechanism remains elusive. This study aimed to explore the potential of XCHG in mitigating yeast-induced fever and the underlying metabolic pathways. The chemical composition of XCHG was ascertained using ultra-fast liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry (UFLC-Q-TOF-MS/MS), followed by integrated network analysis to predict potential targets. We then conducted experimental validation using pharmacological assays and metabolomics analysis in a yeast-induced mouse fever model. The study identified 133 compounds in XCHG, resulting in the development of a comprehensive network of herb–compound–biological functional modules. Subsequently, molecular dynamic (MD) simulations confirmed the stability of the complexes, including γ-aminobutyric acid B receptor 2 (GABBR2)–saikosaponin C, prostaglandin endoperoxide synthases (PTGS2)–lobetyolin, and NF-κB inhibitor IκBα (NFKBIA)–glycyrrhizic acid. Animal experiments demonstrated that XCHG reduced yeast-induced elevation in NFKBIA’s downstream regulators [interleukin (IL)-1β and IL-8], inhibited PTGS2 activity, and consequently decreased prostaglandin E2 (PGE2) levels. XCHG also downregulated the levels of 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), corticotropin releasing hormone (CRH), and adrenocorticotrophin (ACTH). These corroborated the network analysis results indicating XCHG’s effectiveness against fever in targeting NFKBIA, PTGS2, and GABBR2. The hypothalamus metabolomics analysis identified 14 distinct metabolites as potential antipyretic biomarkers of XCHG. In conclusion, our findings suggest that XCHG alleviates yeast-induced fever by regulating inflammation/immune responses, neuromodulation, and metabolism modules, providing a scientific basis for the anti-inflammatory and antipyretic properties of XCHG.

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The role of lipid second messengers in aldosterone synthesis and secretion

Cited by 15 publications

References 123 publications

Determination of endogenous sphingolipid content in stroke rats and HT22 cells subjected to oxygen-glucose deprivation by LC‒MS/MS

Determination of endogenous sphingolipid content in stroke rats and HT22 cells subjected to oxygen-glucose deprivation by LC‒MS/MS

Nephrectomy and high-salt diet inducing pulmonary hypertension and kidney damage by increasing Ang II concentration in rats

Unraveling the Mechanism of Xiaochaihu Granules in Alleviating Yeast-Induced Fever Based on Network Analysis and Experimental Validation

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