Nitric Oxide Signaling Depends on Biotin in Jurkat Human Lymphoma Cells

Rodriguez-Melendez, Rocio; Zempleni, Janos

doi:10.3945/jn.108.101840

Cited by 11 publications

(6 citation statements)

References 43 publications

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“…The increased vascularization observed in histology prompted us to determine nitric oxide concentrations because nitric oxide has been proposed to participate in the biotin transduction signaling pathway cGMP/PKG [31]. However, no differences were found in nitric oxide concentration between the control and the supplemented group (Figure 5): control = 24.5 ± 0.55; supplemented = 25.6 ± 1.50.…”

Section: Resultsmentioning

confidence: 99%

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Dietary Biotin Supplementation Modifies Hepatic Morphology without Changes in Liver Toxicity Markers

Riverón-Negrete

Sicilia-Argumedo

Álvarez-Delgado

et al. 2016

BioMed Research International

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Pharmacological concentrations of biotin have pleiotropic effects. Several reports have documented that biotin supplementation decreases hyperglycemia. We have shown that a biotin-supplemented diet increased insulin secretion and the mRNA abundance of proteins regulating insulin transcription and secretion. We also found enlarged pancreatic islets and modified islet morphology. Other studies have shown that pharmacological concentrations of biotin modify tissue structure. Although biotin administration is considered safe, little attention has been given to its effect on tissue structure. In this study, we investigated the effect of biotin supplementation on hepatic morphology and liver toxicity markers. Male BALB/cAnN Hsd mice were fed a control or a biotin-supplemented diet for 8 weeks. Versus the control mice, biotin-supplemented mice had an altered portal triad with dilated sinusoids, increased vascularity, and bile conducts. Furthermore, we observed an increased proportion of nucleomegaly and binucleated hepatocytes. In spite of the liver morphological changes, no differences were observed in the serum liver damage indicators, oxidative stress markers, or antioxidant enzymes. Our data demonstrate for the first time that biotin supplementation affects liver morphology in normal mice, and that these modifications are not paralleled with damage markers.

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Section: Resultsmentioning

confidence: 99%

“…Studies in Jurkat cells have found that the effects of biotin are dependent of nitric oxide concentrations [31]. However, other studies in rats receiving eight weeks of biotin in water (approximately 1.2 mg/kg body weight) indicate that biotin effects are independent of nitric oxide [40].…”

Section: Discussionmentioning

confidence: 99%

Dietary Biotin Supplementation Modifies Hepatic Morphology without Changes in Liver Toxicity Markers

Riverón-Negrete

Sicilia-Argumedo

Álvarez-Delgado

et al. 2016

BioMed Research International

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“…Biotin-dependent pathways include signaling by biotinyl-adenosine monophosphate (15), nitric 1 oxide (16), and the classical transcription factors nuclear factor-kB (17), Sp1 and Sp3 (18), and Jun/Fos (19). Recently, it has been demonstrated that HCS (20,21) also catalyzes the binding of biotin to the following K residues in histones (22,23): K9, K13, K125, K127, and K129 in histone H2A (24); K4, K9, K18, and perhaps K23 in histone H3 (21,25); and K8 and K12 in histone H4 (26).…”

Section: Introductionmentioning

confidence: 99%

Biotin Requirements Are Lower in Human Jurkat Lymphoid Cells but Homeostatic Mechanisms Are Similar to Those of HepG2 Liver Cells

Mall

Chew

Zempleni

2010

The Journal of Nutrition

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The following proteins are candidates for maintaining biotin homeostasis in humans: the biotin transporters sodium-dependent multivitamin transporter (SMVT) and monocarboxylate transporter 1, the biotinyl-protein ligase holocarboxylase synthetase (HCS), and the lysine-epsilon-biotin hydrolase biotinidase. Liver cells are supplied through the portal vein with high levels of water-soluble vitamins compared with those of peripheral tissues. We hypothesized that the mechanisms of biotin homeostasis are qualitatively and quantitatively different in cells derived from human liver (HepG2 cells) and lymphoid tissues (Jurkat cells). Cells were cultured in biotin-defined media, representing deficient (D), normal (N), and supplemented (S) individuals. Biotinylation of carboxylases depended on biotin availability in both cell types, but HepG2 cells required 3 times more biotin than Jurkat cells to maintain normal levels of holocarboxylases. The expression of biotin transporters was less in both types in medium S compared with cells in media D and N; in contrast, the expression of HCS was higher in cells in medium S compared with the other cells. The abundance of 3-methylcrotonyl-CoA carboxylase mRNA was lower in cells in medium D than cells in media N and S. The enrichment of biotinylated histones was higher at the SMVT promoter 1 in HepG2 and Jurkat cells in medium S compared with the corresponding cells in media D and N, presumably repressing the SMVT gene. The mechanisms of biotin homeostasis are qualitatively similar but quantitatively different in HepG2 and Jurkat cells; HCS, histone biotinylation, and biotin transporters play a role in homeostasis in both.

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“…The roles of HCS in macronutrient metabolism are mediated by HCS-dependent biotinylation of acetyl-CoA carboxylases 1 and 2 (fatty acid synthesis and oxidation, respctively), pyruvate carboxylase (gluconeogenesis), propionyl-CoA carboxylase (odd-chain fatty acids), and 3-methylcrotonyl-CoA carboxylase (leucine metabolism) (1,9,10). The roles of HCS in epigenetics and gene regulation are mediated by HCS-dependent biotinylation of histones (11,12,(39)(40)(41) and HCS-dependent generation of the intermediate biotinyl-AMP (15,42). Decreased biotinylation of histones causes abnormal phenotypes and gene expression patterns (12) that are distinct from those seen in carboxylase deficiency (43).…”

Section: Discussionmentioning

confidence: 99%

Biotin Regulates the Expression of Holocarboxylase Synthetase in the miR-539 Pathway in HEK-293 Cells

Bao

Rodriguez-Melendez

Wijeratne

et al. 2010

The Journal of Nutrition

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Holocarboxylase synthetase (HCS) catalyzes the covalent binding of biotin to carboxylases and histones. In mammals, the expression of HCS depends on biotin, but the mechanism of regulation is unknown. Here we tested the hypothesis that microRNA (miR) plays a role in the regulation of the HCS gene. Human embryonic kidney cells were used as the primary model, but cell lines from other tissues and primary human cells were also tested. In silico searches revealed an evolutionary conserved binding site for miR-539 in the 3 prime -untranslated region (3 prime -UTR) of HCS mRNA. Transgenic cells and reporter gene constructs were used to demonstrate that miR-539 decreases the expression of HCS at the level of transcription rather than translation; these findings were corroborated in nontransgenic cells. When miR-539 was overexpressed in transgenic cells, the abundance of both HCS and biotinylated histones decreased. The abundance of miR-539 was tissue dependent: fibroblasts gt kidney cells gt intestinal cells gt lymphoid cells. Dose-response studies revealed that the abundance of miR-539 was significantly higher at physiological concentrations of biotin than both biotin-deficient and biotin-supplemented media in all cell lines tested. In kidney cells, the expression of HCS was lower in cells in physiological medium than in deficient and supplemented medium. In contrast, in fibroblasts, lymphoid cells, and intestinal cells, there was no apparent link between miR-539 abundance and HCS expression, suggesting that factors other than miR-539 also contribute to the regulation of HCS expression in some tissues. Collectively, the results of this study suggest that miR-539 is among the factors sensing biotin and regulating HCS.

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Nitric Oxide Signaling Depends on Biotin in Jurkat Human Lymphoma Cells

Cited by 11 publications

References 43 publications

Dietary Biotin Supplementation Modifies Hepatic Morphology without Changes in Liver Toxicity Markers

Dietary Biotin Supplementation Modifies Hepatic Morphology without Changes in Liver Toxicity Markers

Biotin Requirements Are Lower in Human Jurkat Lymphoid Cells but Homeostatic Mechanisms Are Similar to Those of HepG2 Liver Cells

Biotin Regulates the Expression of Holocarboxylase Synthetase in the miR-539 Pathway in HEK-293 Cells

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