Extracellular signal-related kinase 2/specificity protein 1/specificity protein 3/repressor element-1 silencing transcription factor pathway is involved in Aroclor 1254-induced toxicity in SH-SY5Y neuronal cells

2014 ◽  
Vol 93 (1) ◽  
pp. 167-177 ◽  
Author(s):  
Luigi Formisano ◽  
Natascia Guida ◽  
Giusy Laudati ◽  
Francesca Boscia ◽  
Alba Esposito ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Neuronal Cells ◽  
Aroclor 1254 ◽  
Specificity Protein 1 ◽  
Extracellular Signal ◽  
Specificity Protein ◽  
Repressor Element

Spot 14 protein interacts and co-operates with chicken ovalbumin upstream promoter-transcription factor 1 in the transcription of the L-type pyruvate kinase gene through a specificity protein 1 (Sp1) binding site

2001 ◽  
Vol 358 (1) ◽  
pp. 175-183 ◽  
Author(s):  
Emmanuel COMPE ◽  
Georges de SOUSA ◽  
Kamel FRANCÇOIS ◽  
Régis ROCHE ◽  
Roger RAHMANI ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Pyruvate Kinase ◽  
Nuclear Proteins ◽  
Kinase Gene ◽  
Specificity Protein 1 ◽  
Upstream Promoter ◽  
Spot 14 ◽  
Specificity Protein ◽  
Transcription Factor 1 ◽  
Chicken Ovalbumin

In hepatocytes, the amount of the Spot 14 (S14) protein is closely related to the full expression of enzymes involved in the glycolytic and lipogenic pathways. In the present study we address the role played by this protein in the control of transcription of the L-type pyruvate kinase (L-PK) gene in primary hepatocytes. We show that human S14, which by itself does not bind to the L-PK promoter, physically interacts with the human chicken ovalbumin upstream promoter-transcription factor 1 (COUP-TF1) and induces the switch of this factor from a repressor to an activator. However, the enhancing activity of S14 and COUP-TF1 depends on the presence of a proximal GC-rich box (the L0 element) that specifically binds nuclear proteins from the livers of rats fed a glucose-rich diet. Moreover, the L0 element, which strongly binds dephosphorylated specificity protein 1 (Sp1), loses all affinity when this factor is phosphorylated by cAMP-dependent protein kinase. Mutations that affect binding of Sp1 and nuclear proteins to the L0 box also decrease basal transcription and impair glucose responsiveness of the promoter. These results therefore shed light on the mechanism by which the S14 protein, whose concentration rapidly rises after glucose intake, contributes to the full activity of the L-PK promoter.

scholarly journals Thiamine transporter 2 is involved in high glucose-induced damage and altered thiamine availability in cell models of diabetic retinopathy

2019 ◽  
Vol 17 (1) ◽  
pp. 147916411987842 ◽  
Author(s):  
Elena Beltramo ◽  
Aurora Mazzeo ◽  
Tatiana Lopatina ◽  
Marina Trento ◽  
Massimo Porta
Keyword(s):  
Transcription Factor ◽  
Diabetic Retinopathy ◽  
High Glucose ◽  
Cell Models ◽  
Blood Retinal Barrier ◽  
Transketolase Activity ◽  
Specificity Protein 1 ◽  
Thiamine Transport ◽  
Factor Specificity ◽  
Specificity Protein

Thiamine prevents high glucose-induced damage in microvasculature, and progression of retinopathy and nephropathy in diabetic animals. Impaired thiamine availability causes renal damage in diabetic patients. Two single-nucleotide polymorphisms in SLC19A3 locus encoding for thiamine transporter 2 are associated with absent/minimal diabetic retinopathy and nephropathy despite long-term type 1 diabetes. We investigated the involvement of thiamine transporter 1 and thiamine transporter 2, and their transcription factor specificity protein 1, in high glucose-induced damage and altered thiamine availability in cells of the inner blood–retinal barrier. Human endothelial cells, pericytes and Müller cells were exposed to hyperglycaemic-like conditions and/or thiamine deficiency/over-supplementation in single/co-cultures. Expression and localization of thiamine transporter 1, thiamine transporter 2 and transcription factor specificity protein 1 were evaluated together with intracellular thiamine concentration, transketolase activity and permeability to thiamine. The effects of thiamine depletion on cell function (viability, apoptosis and migration) were also addressed. Thiamine transporter 2 and transcription factor specificity protein 1 expression were modulated by hyperglycaemic-like conditions. Transketolase activity, intracellular thiamine and permeability to thiamine were decreased in cells cultured in thiamine deficiency, and in pericytes in hyperglycaemic-like conditions. Thiamine depletion reduced cell viability and proliferation, while thiamine over-supplementation compensated for thiamine transporter 2 reduction by restoring thiamine uptake and transketolase activity. High glucose and reduced thiamine determine impairment in thiamine transport inside retinal cells and through the inner blood–retinal barrier. Thiamine transporter 2 modulation in our cell models suggests its major role in thiamine transport in retinal cells and its involvement in high glucose-induced damage and impaired thiamine availability.

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