T-2 Toxin Induces Epiphyseal Plate Lesions via Decreased SECISBP2-Mediated Selenoprotein Expression in DA Rats, Exacerbated by Selenium Deficiency

Objective Both selenium (Se) deficiency and mycotoxin T2 lead to epiphyseal plate lesions, similar to Kashin-Beck disease (KBD). However, regulation of selenoproteins synthesis mediated by SECISBP2, in response to these 2 environmental factors, remained unclear. The present study proposed to explore the mechanism behind the cartilage degradation resulting from Se deficiency and mycotoxin T2 exposure. Design Deep chondrocyte necrosis and epiphyseal plate lesions were replicated in Dark Agouti (DA) rats by feeding them T2 toxin/Se deficiency artificial synthetic diet for 2 months. Results Se deficiency led to decreased expression of COL2α1, while T2 treatment reduced the heparan sulfate 6-O-sulfotransferase 2 (HS6ST2) expression, both of which affected the cartilage extracellular matrix metabolism in the rat models. The expression of Col2α1, Acan, Hs6st2, Secisbp2, Gpx1, and Gpx4 were all significantly decreased in cartilage tissues from DA rats, fed a Se-deficient diet or exposed to T2 toxin, contrary to Adamts4, whose expression was increased in both conditions. In addition, T2 treatment led to the decreased expression of SBP2, GPX1, GPX4, and total GPXs activity in C28/I2 cells. Conclusion DA rats exposed to T2 toxin and/or Se-deficient conditions serve as the perfect model of KBD. The 2 environmental risk factors of KBD, which serve as a “double whammy,” can intensify the extracellular matrix metabolic imbalance and the antioxidant activity of chondrocytes, leading to articular cartilage degradation and epiphyseal plate abnormalities similar to those observed in KBD.

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Effect of selenium deficiency on hepatic lipid and lipoprotein metabolism in the rat

British Journal Of Nutrition ◽

10.1079/bjn19970166 ◽

1997 ◽

Vol 78 (3) ◽

pp. 493-500 ◽

Cited By ~ 20

Author(s):

F. Nassir ◽

C. Moundras ◽

D. Bayle ◽

C. Sérougne ◽

E. Gueux ◽

...

Keyword(s):

Plasma Cholesterol ◽

Liver Microsomes ◽

Ldl Receptor ◽

Selenium Deficiency ◽

Cholesterol Concentration ◽

Deficient Diet ◽

Hmg Coa Reductase ◽

Hepatic Lipid ◽

Se Deficiency ◽

Coa Reductase

Since experimental Se deficiency results in a significant increase in plasma cholesterol concentration the present investigation was undertaken to assess further the influence of this deficiency on the expression of proteins involved in hepatic lipid metabolism. Se deficiency was induced by feeding weanling male Wistar rats on a deficient diet for 6 weeks. Hypercholesterolaemia associated with Se deficiency was related to increased 3-hydroxy-3-methylglutaryl-coA (HMG-CoA) reductase (EC 1.1.1.34) activity in liver microsomes as compared with control animals. Hepatic lipoprotein receptor levels (LDL-receptor and HDL-binding proteins, HB1 and HB2) were not significantly affected by Se deficiency, as assessed by immunoblotting. Plasma triacylglycerol concentrations tended to decrease in Se-deficient rats in concert with their reduced post-Triton secretion. There was no significant effect of Se deficiency on the hepatic synthesis of apolipoproteins. These results point to the need for further investigations into the mechanism related to the increased activity of HMG-CoA reductase and the enhanced cholesterogenesis in the liver of Se-deficient rats likely to result from this.Selenium: Cholesterol: Triacylglycerol: HMG-CoA reductase

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Neonatal Selenoenzyme Expression Is Variably Susceptible to Duration of Maternal Selenium Deficiency

Antioxidants ◽

10.3390/antiox10020288 ◽

2021 ◽

Vol 10 (2) ◽

pp. 288

Author(s):

Laura G. Sherlock ◽

Durganili Balasubramaniyan ◽

Lijun Zheng ◽

Miguel Zarate ◽

Thomas Sizemore ◽

...

Keyword(s):

Thioredoxin Reductase ◽

Selenium Deficiency ◽

Deficient Diet ◽

Hepatic Expression ◽

Multiple Organs ◽

Thioredoxin Reductase 1 ◽

Neonatal Liver ◽

Se Deficiency ◽

The Impact ◽

Gpx Activity

Maternal selenium (Se) deficiency is associated with decreased neonatal Se levels, which increases the risk for neonatal morbidities. There is a hierarchy to selenoprotein expression after Se deficiency in adult rodents, depending on the particular protein and organ evaluated. However, it is unknown how limited Se supply during pregnancy impacts neonatal selenoprotein expression. We used an Se-deficient diet to induce perinatal Se deficiency (SeD), initiated 2–4 weeks before onset of breeding and continuing through gestation. Neonatal plasma, liver, heart, kidney, and lung were collected on the day of birth and assessed for selenoproteins, factors required for Se processing, and non-Se containing antioxidant enzymes (AOE). Maternal SeD reduced neonatal circulating and hepatic glutathione peroxidase (GPx) activity, as well as hepatic expression of Gpx1 and selenophosphate synthetase 2 (Sps2). In contrast, the impact of maternal SeD on hepatic thioredoxin reductase 1, hepatic non-Se containing AOEs, as well as cardiac, renal, and pulmonary GPx activity, varied based on duration of maternal exposure to SeD diet. We conclude that the neonatal liver and circulation demonstrate earlier depletion in selenoenzyme activity after maternal SeD. Our data indicate that prolonged maternal SeD may escalate risk to the neonate by progressively diminishing Se-containing AOE across multiple organs.

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Connective Tissue Metabolism and Gingival Overgrowth

Critical Reviews in Oral Biology & Medicine ◽

10.1177/154411130401500305 ◽

2004 ◽

Vol 15 (3) ◽

pp. 165-175 ◽

Cited By ~ 91

Author(s):

P. C. Trackman ◽

A. Kantarci

Keyword(s):

Extracellular Matrix ◽

Connective Tissue ◽

Oral Hygiene ◽

Tissue Specificity ◽

Gingival Fibroblast ◽

Drug Induced ◽

Gingival Overgrowth ◽

Connective Tissue Metabolism ◽

Matrix Metabolism ◽

Systemic Health

Gingival overgrowth occurs mainly as a result of certain anti-seizure, immunosuppressive, or antihypertensive drug therapies. Excess gingival tissues impede oral function and are disfiguring. Effective oral hygiene is compromised in the presence of gingival overgrowth, and it is now recognized that this may have negative implications for the systemic health of affected patients. Recent studies indicate that cytokine balances are abnormal in drug-induced forms of gingival overgrowth. Data supporting molecular and cellular characteristics that distinguish different forms of gingival overgrowth are summarized, and aspects of gingival fibroblast extracellular matrix metabolism that are unique to gingival tissues and cells are reviewed. Abnormal cytokine balances derived principally from lymphocytes and macrophages, and unique aspects of gingival extracellular matrix metabolism, are elements of a working model presented to facilitate our gaining a better understanding of mechanisms and of the tissue specificity of gingival overgrowth.

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Signaling Mechanisms in the Regulation of Renal Matrix Metabolism in Diabetes

Experimental Diabetes Research ◽

10.1155/2012/749812 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 23

Author(s):

Meenalakshmi M. Mariappan

Keyword(s):

Extracellular Matrix ◽

Signaling Pathways ◽

Matrix Protein ◽

Structural Changes ◽

Mammalian Target Of Rapamycin ◽

Adverse Outcomes ◽

Matrix Proteins ◽

Extracellular Matrix Protein ◽

Renal Hypertrophy ◽

Matrix Metabolism

Renal hypertrophy and accumulation of extracellular matrix proteins are among cardinal manifestations of diabetic nephropathy. TGF beta system has been implicated in the pathogenesis of these manifestations. Among signaling pathways activated in the kidney in diabetes, mTOR- (mammalian target of rapamycin-)regulated pathways are pivotal in orchestrating high glucose-induced production of ECM proteins leading to functional and structural changes in the kidney culminating in adverse outcomes. Understanding signaling pathways that influence individual matrix protein expression could lead to the development of new interventional strategies. This paper will highlight some of the diverse components of the signaling network stimulated by hyperglycemia with an emphasis on extracellular matrix protein metabolism in the kidney in diabetes.

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Inhibition of hepatic deiodination of thyroxine is caused by selenium deficiency in rats

Biochemical Journal ◽

10.1042/bj2480443 ◽

1987 ◽

Vol 248 (2) ◽

pp. 443-447 ◽

Cited By ~ 99

Author(s):

G J Beckett ◽

S E Beddows ◽

P C Morrice ◽

F Nicol ◽

J R Arthur

Keyword(s):

Thyroid Hormones ◽

Production Rate ◽

Selenium Deficiency ◽

Enzyme Complex ◽

Measurable Effect ◽

Direct Role ◽

Mechanism Of Inhibition ◽

Se Deficiency

Selenium (Se) deficiency produced up to a 14-fold decrease in hepatic tri-iodothyronine (T3) production from thyroxine (T4) in vitro. The T3 production rate could not be restored by the addition of a variety of cofactors, nor by the addition of control homogenate. The impairment in hepatic T3 production observed in Se deficiency was reflected in the concentrations of thyroid hormones circulating in plasma, T4 being increased approx. 40% and T3 being decreased by 30%. However, the fall in plasma T3 concentrations was smaller than might be expected in view of the marked decreased in T3 production. Se deficiency had no measurable effect on plasma reverse-tri-iodothyronine concentrations. The data suggest that Se deficiency produces an inhibition of both 5- and 5′-deiodination, consistent with the widely held view that these reactions are catalysed by the same enzyme complex. The mechanism of inhibition appears not be mediated by changes in thiol levels, but a direct role of Se in the activity of the deiodinase complex cannot be excluded.

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