Folate deficiency in normal human fibroblasts leads to altered expression of genes primarily linked to cell signaling, the cytoskeleton and extracellular matrix

Katula, Karen S.; Heinloth, Alexandra N.; Paules, Richard S.

doi:10.1016/j.jnutbio.2006.11.002

Cited by 25 publications

(18 citation statements)

References 52 publications

(61 reference statements)

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“…These included collagen VI, α 1 and 2C2 isoforms, vimentin (VIM), tubulin-α (TUBA1B), β -actin (ACTB), vinculin isoform, plastin 3 (PLS3), lamin A/C isoform 2, chaperonin TCP1, caldesmon 1 (CALD1), cofilin 1 and transgelin 2. Changes in cytoskeletal proteins have been also reported for a patient cell line belonging to the cblD complementation group [ 74 ] and also, for human fibroblasts [ 75 ] and colonocytes [ 76 ] under conditions of folate deficiency. Collagen VI, isoform 2C2 was upregulated in cblC fibroblasts.…”

Section: Cytoskeleton: Assembly and Remodelingmentioning

confidence: 66%

Proteomics of vitamin B12 processing

Hannibal

DiBello

Jacobsen³

2013

Clinical Chemistry and Laboratory Medicine

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The causes of cobalamin (B 12 , Cbl) deficiency are multifactorial. Whether nutritional due to poor dietary intake, or functional due to impairments in absorption or intracellular processing and trafficking events, the major symptoms of Cbl deficiency include megaloblastic anemia, neurological deterioration and in extreme cases, failure to thrive and death. The common biomarkers of Cbl deficiency (hyperhomocysteinemia and methylmalonic acidemia) are extremely valuable diagnostic indicators of the condition, but little is known about the changes that occur at the protein level. A mechanistic explanation bridging the physiological changes associated with functional B 12 deficiency with its intracellular processers and carriers is lacking. In this article, we will cover the effects of B 12 deficiency in a cblC -disrupted background (also referred to as MMACHC) as a model of functional Cbl deficiency. As will be shown, major protein changes involve the cytoskeleton, the neurological system as well as signaling and detoxification pathways. Supplementation of cultured MMACHC-mutant cells with hydroxocobalamin (HOCbl) failed to restore these variants to the normal phenotype, suggesting that a defective Cbl processing pathway produces irreversible changes at the protein level.

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Section: Cytoskeleton: Assembly and Remodelingmentioning

confidence: 66%

Proteomics of vitamin B12 processing

Hannibal

DiBello

Jacobsen³

2013

Clinical Chemistry and Laboratory Medicine

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“…FA deficiency seems to alter gene expression by disrupting DNA methylation patterns or by inducing base substitution, DNA breaks, gene deletions and/or gene amplification [reviewed in Crott et al, 2008]. Investigations performed in other systems under FA deficiency demonstrated altered expression of genes such as TGF-␤ 1 and IGF-1 [Santoso and Rohman, 2006], EGF-R [Jaszewski et al, 1999], TGF-␣ [Hise et al, 2001] and WNT5a [Katula et al, 2007], all of which are present during palate development and exert an influence on the mechanisms leading to palatal fusion [Fitzpatrick et al, 1990;Pelton et al, 1990;Shiota et al, 1990;Dixon et al, 1991;He et al, 2008]. Folate depletion in cultured normal human cells was seen to greatly decrease the expression of SMAD4, the molecule transmitting TGF-␤ signals to the cell nucleus [Crott et al, 2008].…”

Section: Discussionmentioning

confidence: 99%

Occurrence of Cleft-Palate and Alteration of Tgf-β3 Expression and the Mechanisms Leading to Palatal Fusion in Mice following Dietary Folic-Acid Deficiency

Maldonado

Murillo

Barrio

et al. 2011

Cells Tissues Organs

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Folic acid (FA) is essential for numerous bodily functions. Its decrease during pregnancy has been associated with an increased risk of congenital malformations in the progeny. The relationship between FA deficiency and the appearance of cleft palate (CP) is controversial, and little information exists on a possible effect of FA on palate development. We investigated the effect of a 2–8 weeks’ induced FA deficiency in female mice on the development of CP in their progeny as well as the mechanisms leading to palatal fusion, i.e. cell proliferation, cell death, and palatal-shelf adhesion and fusion. We showed that an 8 weeks’ maternal FA deficiency caused complete CP in the fetuses although a 2 weeks’ maternal FA deficiency was enough to alter all the mechanisms analyzed. Since transforming growth factor-β₃ (TGF-β₃) is crucial for palatal fusion and since most of the mechanisms impaired by FA deficiency were also observed in the palates of Tgf-β₃null mutant mice, we investigated the presence of TGF-β₃ mRNA, its protein and phospho-SMAD2 in FA-deficient (FAD) mouse palates. Our results evidenced a large reduction in Tgf-β₃ expression in palates of embryos of dams fed an FAD diet for 8 weeks; Tgf-β₃ expression was less reduced in palates of embryos of dams fed an FAD diet for 2 weeks. Addition of TGF-β₃ to palatal-shelf cultures of embryos of dams fed an FAD diet for 2 weeks normalized all the altered mechanisms. Thus, an insufficient folate status may be a risk factor for the development of CP in mice, and exogenous TGF-β₃ compensates this deficit in vitro.

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“…More recently, using a Wnt-reporter mouse model and a colorectal cancer mouse model, I further demonstrated that the combined one-carbon vitamin depletion (folate in conjunction with B2, B6 and B12 depletion) does increase the Wnt-signaling accompanying with elevated tumor incidence [20]. Moreover, other investigators have also observed significant changes in the expression of several modulators of the Wnt pathway, such as WISP1, WNT5Aand DKK-1, as a result of folate depletion [21]. Indirect evidence that folate depletion alters the Wnt pathway can also be drawn from studies of the rodent model of folate-sensitive neural tube birth defects, the crooked tail mouse, the genetic basis of which is a mutation in Lrp6, a Wnt co-receptor [22].…”

mentioning

confidence: 93%

One-Carbon Vitamins, Epigenetic/Genetic Integrity and Colon Cancer: Research is Needed to Understand the Effect on Tumorigenic Signaling Pathways

Liu¹

2012

Vitamin Trace Element

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Folate deficiency in normal human fibroblasts leads to altered expression of genes primarily linked to cell signaling, the cytoskeleton and extracellular matrix

Cited by 25 publications

References 52 publications

Proteomics of vitamin B12 processing

Proteomics of vitamin B12 processing

Occurrence of Cleft-Palate and Alteration of <i>Tgf-</i>β<sub><i>3</i></sub> Expression and the Mechanisms Leading to Palatal Fusion in Mice following Dietary Folic-Acid Deficiency

One-Carbon Vitamins, Epigenetic/Genetic Integrity and Colon Cancer: Research is Needed to Understand the Effect on Tumorigenic Signaling Pathways

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