Homocysteine causes disruptions in spinal cord morphology and changes the expression of Pax 1/9 and Sox 9 gene products in the axial mesenchyme

Kobus, Karoline; Ammar, Dib; Nazari, Evelise Maria; Müller, Yara Maria Rauh

doi:10.1002/bdra.23131

Cited by 10 publications

(3 citation statements)

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“…We showed here that the treatment with Hcy induces an increase in expression of Pax9 and Sox9 proteins. A reduction of expression of Pax1/9 and Sox9 proteins and mRNA in mesenchymal cells of vertebral elements was observed by Kobus et al, () after treatment with 20 µmol d‐l Hcy. The differences in expression of Pax9 and Sox9 can be explained by the different embryonic origin of the mesenchymal cells, i.e.…”

Section: Discussionmentioning

confidence: 60%

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Effects of homocysteine on mesenchymal cell proliferation and differentiation during chondrogenesis on limb development

Bourckhardt

Cecchini

Ammar

et al. 2015

J of Applied Toxicology

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High levels of homocysteine (Hcy) are related to an increased risk of the occurrence of congenital anomalies, including limb defects. However, few evaluations about how toxic levels of Hcy affect limb development have been reported. We investigated whether Hcy can affect the cell cycle proteins and proteins involved in mesenchymal cell differentiation during limb development, in a chicken embryo model. Embryos were treated with 20 µmol d-l Hcy/50 µl saline at embryonic day 2 and analyzed at embryonic day 6. Untreated control embryos received exclusively 50 µl saline solution. To identify cells in proliferation and cell cycle proteins, as well as Pax1/9 and Sox9 proteins, we performed immunolocalization and flow cytometry analyses using the antibodies anti-phosphohistone H3, anti-p53, anti-p21, anti-proliferating cell nuclear antigen, anti-Pax1, anti-Pax9 and anti-Sox9. No significant differences in cell proliferation were observed between Hcy-treated and untreated embryos. We observed a decrease of the proliferating cell nuclear antigen and p21 proteins, both involved in the G1 phase of cell cycle progression. On the other hand, in mesenchymal cells of the limbs, Hcy induces an increase of p53 protein, which can be activated by DNA damage. In cell differentiation, Hcy induced an increase mainly of Pax9 and Sox9 proteins. Our data indicate that the treatment with Hcy changes the mesenchymal cell dynamics during limb development, but does not change the morphology of the cartilage molds. These findings provide information to understand better the cellular basis of the toxicity of Hcy on chondrogenesis during limb development.

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Section: Discussionmentioning

confidence: 60%

“…Our previous studies demonstrated disruptions of Pax1/9 and Sox9 proteins in the axial mesenchyme caused by folate/Hcy imbalance (Kobus et al, ; Müller et al, ). In embryos treated with 20 µmol d,l ‐Hcy we also detected the appearance of limb defects, which stimulated our interest for further studies.…”

Section: Introductionmentioning

confidence: 93%

Effects of homocysteine on mesenchymal cell proliferation and differentiation during chondrogenesis on limb development

Bourckhardt

Cecchini

Ammar

et al. 2015

J of Applied Toxicology

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“…In vitro and animal studies have shown that the homocysteine level in the embryonic stage affects the expression of PAX [ 28 , 29 ]. The relationship between homocysteine and PAX3 mutation in WS is unclear.…”

Section: Discussionmentioning

confidence: 99%

A novel PAX3 mutation in a Korean patient with Waardenburg syndrome type 1 and unilateral branch retinal vein and artery occlusion: a case report

Choi

Lee

2018

BMC Ophthalmol

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BackgroundWaardenburg syndrome (WS) is a very rare genetic disorder affecting the neural crest cells. Coexistence of branch retinal vein occlusion (BRVO) and branch retinal artery occlusion (BRAO) in the same eye is also a rare finding. Here we report a case of WS type 1 that was confirmed by a novel mutation with the finding of unilateral BRVO and BRAO.Case presentationA 36-year-old, white-haired Korean man presented with a complaint of loss of vision in the inferior visual field of his right eye and hearing loss. He had telecanthus with a medial eyebrow and a hypochromic left iris. Funduscopy showed an ischemic change at the posterior pole in the right eye with sparing of the foveal center as well as retinal hemorrhages and white patches along the superotemporal arcade. Fundus angiography revealed the presence of both BRVO and BRAO, and optical coherence tomography showed thickening and opacification of the retinal layers corresponding to the ischemic area. A blood workup revealed hyperhomocysteinemia and the presence of antiphospholipid antibodies; both are suggestive as the cause of the BRVO and BRAO. Single nucleotide polymorphism analysis confirmed a novel PAX3 mutation at 2q35 (c.91–95 ACTCC deletion causing a frameshift). These findings confirmed a diagnosis of WS type 1.ConclusionsWS is a heterogeneous inherited disorder of the neural crest cells that causes pigment abnormalities and sensorineural hearing loss. This is the first report of unilateral BRVO and BRAO in a patient with WS. Furthermore, the PAX3 mutation identified in this patient has not been reported previously.

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Homocysteinemia and Its Neurological Effects

Bhargava¹

2018

The Clinical Application of Homocysteine

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Homocysteine causes disruptions in spinal cord morphology and changes the expression of Pax 1/9 and Sox 9 gene products in the axial mesenchyme

Abstract: Our data clarified the relationship between spinal NTD genesis and disruptions of Pax 1/9 and Sox 9 gene products in the axial mesenchyme caused by the FA/Hcy imbalance.

Cited by 10 publications

References 47 publications

Effects of homocysteine on mesenchymal cell proliferation and differentiation during chondrogenesis on limb development

Effects of homocysteine on mesenchymal cell proliferation and differentiation during chondrogenesis on limb development

A novel PAX3 mutation in a Korean patient with Waardenburg syndrome type 1 and unilateral branch retinal vein and artery occlusion: a case report

Homocysteinemia and Its Neurological Effects

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