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Background <p>Exposure to cadmium, a trace metallic element, is a major health concern. Cadmium is associated with a higher risk and predisposition to cardiovascular disease. Identifying molecular targets involved in such an effect is complexified by <i>in utero</i> embryonic and fetal development.</p> Methods <p>To overcome those difficulties, we used the established vertebrate heart model of <i>Xenopus laevis</i> to analyze the neural cell adhesion molecules NCAM and FGF receptors involved in early cardiac development under cadmium treatment. Cadmium exposure is performed from fertilization until the completion of mature heart development at the end of stage 45. Additional molecular modifications occurring within the heart are detected in the expressing signaling system of <i>Xenopus</i> oocytes.</p> Results <p>Exposure to cadmium results in the absence of heart ventricular myocardial trabeculae and disrupts the regulation of NCAM adhesion molecules and FGF receptor signaling in <i>Xenopus</i>. An increase in polysialylation (PSA) of NCAM is observed, accompanied by the deregulation in the expression of Golgi effectors Rab11 GTPase and Golph3. The sialyltransferases <i>ST8Sia2</i> and <i>ST8Sia4</i> are not increased at the transcriptional level but are accumulated in the Golgi apparatus. The highly sialylated NCAM interacts with the FGF receptor, prevents the formation of a complex with Integrin, FAK is <i>O</i>-GlcNAcylated, and the receptor translocation to the nucleus is impaired. Furthermore, the polysialylated-NCAM/FGF receptor signaling recruits higher amounts of Shp2 and leads to Erk2 hyperphosphorylation. Additionally, blocking FAK with a specific antibody in the normal polysialylated-NCAM/FGF receptor signaling causes the deregulated molecular phenotype.</p> Conclusions <p>These results represent a significant advancement for future studies in environmental toxicology and cardiac developmental dysfunctions resulting from cadmium exposure.</p>

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Cadmium impairs heart ventricular formation and disrupts polysialylated-NCAM/FGF receptor signaling in Xenopus tadpoles

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月3日

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  • Pélagie Douchez,
  • Ingrid Fliniaux,
  • Yoshiko Takeda-Uchimura,
  • Alain Martoriati,
  • Matthieu Marin,
  • Anne Harduin-Lepers,
  • Katia Cailliau

摘要

Background

Exposure to cadmium, a trace metallic element, is a major health concern. Cadmium is associated with a higher risk and predisposition to cardiovascular disease. Identifying molecular targets involved in such an effect is complexified by in utero embryonic and fetal development.

Methods

To overcome those difficulties, we used the established vertebrate heart model of Xenopus laevis to analyze the neural cell adhesion molecules NCAM and FGF receptors involved in early cardiac development under cadmium treatment. Cadmium exposure is performed from fertilization until the completion of mature heart development at the end of stage 45. Additional molecular modifications occurring within the heart are detected in the expressing signaling system of Xenopus oocytes.

Results

Exposure to cadmium results in the absence of heart ventricular myocardial trabeculae and disrupts the regulation of NCAM adhesion molecules and FGF receptor signaling in Xenopus. An increase in polysialylation (PSA) of NCAM is observed, accompanied by the deregulation in the expression of Golgi effectors Rab11 GTPase and Golph3. The sialyltransferases ST8Sia2 and ST8Sia4 are not increased at the transcriptional level but are accumulated in the Golgi apparatus. The highly sialylated NCAM interacts with the FGF receptor, prevents the formation of a complex with Integrin, FAK is O-GlcNAcylated, and the receptor translocation to the nucleus is impaired. Furthermore, the polysialylated-NCAM/FGF receptor signaling recruits higher amounts of Shp2 and leads to Erk2 hyperphosphorylation. Additionally, blocking FAK with a specific antibody in the normal polysialylated-NCAM/FGF receptor signaling causes the deregulated molecular phenotype.

Conclusions

These results represent a significant advancement for future studies in environmental toxicology and cardiac developmental dysfunctions resulting from cadmium exposure.