1H NMR study of monocrotaline and its metabolites in human blood

Yang, Yicheng; Crowder, John; Wardle, Nicholas J.; Yang, Li; White, Kenneth; Wang, Zhengtao; Bligh, S. W. Annie

doi:10.1016/j.fct.2011.07.063

Cited by 6 publications

(14 citation statements)

References 36 publications

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“…We found, however, that MCTP aggregated in water to form red insoluble polymers, as reported previously, and this prevented us from exploring its binding to CaSR by proton NMR spectroscopy or labeling it with FITC. This might have been the reason for the use of monocrotaline instead of MCTP in experiments using proton NMR spectroscopy in a previous study . Of note, our conclusion about the binding of monocrotaline to CaSR in protein preparation and in cultured PAECs was further supported by our cellular thermal shift assay experiments aiming to confirm the binding of MCTP to CaSR in vivo using the pulmonary arteries isolated from monocrotaline‐administered rats, under which MCTP was generally believed to be the major form of monocrotaline metabolites targeting pulmonary endothelial cells.…”

Section: Discussionsupporting

confidence: 54%

“…This might have been the reason for the use of monocrotaline instead of MCTP in experiments using proton NMR spectroscopy in a previous study. 49 Of note, our conclusion about the binding of monocrotaline to CaSR in protein preparation and in cultured PAECs was further supported by our cellular thermal shift assay experiments aiming to confirm the binding of MCTP to CaSR in vivo using the pulmonary arteries isolated from monocrotaline-administered rats, under which MCTP was generally believed to be the major form of monocrotaline metabolites targeting pulmonary endothelial cells. To the best of our knowledge, the binding of MCTP to any molecule in vivo has not been evaluated in any previous studies.…”

Section: Discussionmentioning

confidence: 56%

“…3,4,6,9,[30][31][32][33][34][35][36] Both monocrotaline and MCTP were used in previous studies with isolated blood cells or cultured PAECs in vitro. 12,13,49 In the pilot experiments with CaSR protein preparations, we prepared MCTP and tried to use MCTP instead of monocrotaline, as Segall and colleagues did previously. 12,13 We found, however, that MCTP aggregated in water to form red insoluble polymers, as reported previously, 50,51 and this prevented us from exploring its binding to CaSR by proton NMR spectroscopy or labeling it with FITC.…”

Section: Discussionmentioning

confidence: 99%

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Monocrotaline Induces Endothelial Injury and Pulmonary Hypertension by Targeting the Extracellular Calcium–Sensing Receptor

Xiao

Tian

et al. 2017

JAHA

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BackgroundMonocrotaline has been widely used to establish an animal model of pulmonary hypertension. The molecular target underlying monocrotaline‐induced pulmonary artery endothelial injury and pulmonary hypertension remains unknown. The extracellular calcium–sensing receptor (CaSR) and particularly its extracellular domain hold the potential structural basis for monocrotaline to bind. This study aimed to reveal whether monocrotaline induces pulmonary hypertension by targeting the CaSR.Methods and ResultsNuclear magnetic resonance screening through WaterLOGSY (water ligand‐observed gradient spectroscopy) and saturation transfer difference on protein preparation demonstrated the binding of monocrotaline to the CaSR. Immunocytochemical staining showed colocalization of monocrotaline with the CaSR in cultured pulmonary artery endothelial cells. Cellular thermal shift assay further verified the binding of monocrotaline to the CaSR in pulmonary arteries from monocrotaline‐injected rats. Monocrotaline enhanced the assembly of CaSR, triggered the mobilization of calcium signaling, and damaged pulmonary artery endothelial cells in a CaSR‐dependent manner. Finally, monocrotaline‐induced pulmonary hypertension in rats was significantly attenuated or abolished by the inhibitor, the general or lung knockdown or knockout of CaSR.ConclusionsMonocrotaline aggregates on and activates the CaSR of pulmonary artery endothelial cells to trigger endothelial damage and, ultimately, induces pulmonary hypertension.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Monocrotaline Induces Endothelial Injury and Pulmonary Hypertension by Targeting the Extracellular Calcium–Sensing Receptor

Xiao

Tian

et al. 2017

JAHA

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“…129 A recent investigation that utilized qHNMR as the analytical tool showed that blood and red blood cells mediated the transport of hepatotoxic plant pyrrolizidine alkaloids and its reactive metabolites in humans. 130 …”

Section: Applications Of Qhnmrmentioning

confidence: 99%

Quantitative ¹H NMR. Development and Potential of an Analytical Method: An Update

et al. 2012

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Covering the literature from mid-2004 until the end of 2011, this review continues a previous literature overview on quantitative 1 H NMR (qHNMR) methodology and its applications in the analysis of natural products. Among the foremost advantages of qHNMR is its accurate function with external calibration, the lack of any requirement for identical reference materials, a high precision and accuracy when properly validated, and an ability to quantitate multiple analytes simultaneously. As a result of the inclusion of over 170 new references, this updated review summarizes a wealth of detailed experiential evidence and newly developed methodology that supports qHNMR as a valuable and unbiased analytical tool for natural product and other areas of research.

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“…MCTP binds to erythrocytes or red blood cells (RBCs) (10,27). However, it cannot cause hypoxemia, implying that it does not affect their oxygen carrying capacity.…”

Section: Introductionmentioning

confidence: 99%

Monocrotaline pyrrole induces pulmonary endothelial damage through binding to and release from erythrocytes in lung during venous blood reoxygenation

Xiao

Zhu

et al. 2019

American Journal of Physiology-Lung Cellular and Molecular Phys

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Monocrotaline has been widely used to establish an animal model of pulmonary hypertension, most frequently in rats. An important feature of this model resides in the selectivity of monocrotaline injury toward the pulmonary vascular endothelium versus the systemic vasculature when administrated at standard dosage. The toxic metabolite of monocrotaline, monocrotaline pyrrole, is transported by erythrocytes. This study aimed to reveal whether partial pressure of oxygen of blood determined the binding and release of monocrotaline pyrrole from erythrocytes in rats with one subcutaneous injection of monocrotatline at the standard dosage of 60 mg/kg. Our experiments demonstrated that monocrotaline pyrrole bound to and released from erythrocytes at the physiological levels of partial pressure of oxygen in venous and arterial blood, respectively, and then aggregated on pulmonary artery endothelial cells. Monocrotaline pyrrole-induced damage of endothelial cells was also dependent on partial pressure of oxygen. In conclusion, our results demonstrate the importance of oxygen partial pressure on monocrotaline pyrrole binding to erythrocytes and on aggregation and injury of pulmonary endothelial cells. We suggest that these mechanisms contribute to pulmonary selectivity of this toxic injury model of pulmonary hypertension.

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1H NMR study of monocrotaline and its metabolites in human blood

Cited by 6 publications

References 36 publications

Monocrotaline Induces Endothelial Injury and Pulmonary Hypertension by Targeting the Extracellular Calcium–Sensing Receptor

Monocrotaline Induces Endothelial Injury and Pulmonary Hypertension by Targeting the Extracellular Calcium–Sensing Receptor

Quantitative ¹H NMR. Development and Potential of an Analytical Method: An Update

Monocrotaline pyrrole induces pulmonary endothelial damage through binding to and release from erythrocytes in lung during venous blood reoxygenation

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1H NMR study of monocrotaline and its metabolites in human blood

Cited by 6 publications

References 36 publications

Monocrotaline Induces Endothelial Injury and Pulmonary Hypertension by Targeting the Extracellular Calcium–Sensing Receptor

Monocrotaline Induces Endothelial Injury and Pulmonary Hypertension by Targeting the Extracellular Calcium–Sensing Receptor

Quantitative 1H NMR. Development and Potential of an Analytical Method: An Update

Monocrotaline pyrrole induces pulmonary endothelial damage through binding to and release from erythrocytes in lung during venous blood reoxygenation

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Quantitative ¹H NMR. Development and Potential of an Analytical Method: An Update