Could thiamine pyrophosphate be a regulator of the nitric oxide synthesis in the endothelial cell of diabetic patients?

2011 ◽  
Vol 76 (5) ◽  
pp. 629-631 ◽  
Author(s):  
Susana Alcázar-Leyva ◽  
Noé Alvarado-Vásquez
Author(s):  
Susana Alcázar-Leyva ◽  
Estrella Zapata ◽  
Demetrio Bernal-Alcántara ◽  
Patricia Gorocica ◽  
Noé Alvarado-Vásquez

Abstract. Although thiamine pyrophosphate (TPP) is considered a protective agent for endothelial cells, it is still unknown if this is associated with nitric oxide (NO) synthesis. Our aim was to evaluate the synthesis of NO in endothelial cells incubated with TPP and high glucose concentrations. Endothelial cells from the umbilical cord vein from newborns (n = 20), were incubated with 5, 15 or 30 mmol/L glucose, in absence or presence of 0.625 mg/ml of TPP. Our results showed a significant increase in cell proliferation (> 40%; P < 0.05), and cell viability (> 90%; P < 0.001) after 48 h in endothelial cells cultured with glucose plus TPP. Likewise, in the presence of glucose and TPP an important rise in the consumption of glucose by the endothelial cells was observed after 24 h (> 7%; P < 0.001) and 48 h (> 10%; P < 0.05). Additionally, the levels of lactate after incubation with glucose and TPP showed only slight variations after 48 h (P < 0.05). However, these changes were clearly different from those observed in the absence of TPP. Interestingly, we found that the changes mentioned were linked with reduced levels of nitrites both at 24 h (< 171 pmol/μg protein; P < 0.001), and 48 h (< 250 pmol/μg protein; P < 0.05), which was associated with a reduced expression of mRNA of eNOS in endothelial cells incubated with TPP and high glucose. In conclusion, the presence of TPP regulates the consumption of glucose and the synthesis of NO, which would explain its protective effect in the endothelium of diabetic patients.


2004 ◽  
Vol 24 (10) ◽  
pp. 1816-1822 ◽  
Author(s):  
Fortunato Scalera ◽  
Jürgen Borlak ◽  
Bibiana Beckmann ◽  
Jens Martens-Lobenhoffer ◽  
Thomas Thum ◽  
...  

2010 ◽  
Vol 94 (5) ◽  
pp. 1578-1582 ◽  
Author(s):  
Mayra Beraldo Andozia ◽  
Carolina Sales Vieira ◽  
Silvio Antônio Franceschini ◽  
Maria Regina Torqueti Tolloi ◽  
Marcos Felipe Silva de Sá ◽  
...  

1992 ◽  
Vol 3 (1) ◽  
pp. 42-50
Author(s):  
T Takenaka ◽  
Y Hashimoto ◽  
M Epstein

The mechanisms mediating cyclosporin A (CsA)-induced nephrotoxicity have not been established, but damage to endothelial cells by CsA has been proposed as an important factor. In the study presented here, whether endothelial cell function is impaired in the renal vasculature of CsA-treated rats is investigated. The vasodilatory effects of acetylcholine (ACH) on norepinephrine (NE)-induced microvascular constriction in isolated perfused hydronephrotic rat kidneys pretreated with CsA were therefore examined. Hydronephrosis was established to permit direct visualization of renal microvessels. Nephrotoxicity was induced by s.c. injection of CsA (60 mg/kg/day for 5 days). NE (0.3 microM)-induced afferent arteriolar (AA) constriction was exaggerated in CsA rats as compared with that in vehicle (olive oil)-treated control rats. (reduction in diameter of -34 +/- 3 (SE) versus -26 +/- 2%; P less than 0.05). Similarly, efferent arteriolar (EA) constriction by NE in CsA rats exceeded that of controls (-34 +/- 2 versus -22 +/- 3%; P less than 0.01). The vasodilatory responses evoked by ACH were blunted in CsA rats. The AA response to ACH in CsA rats was significantly decreased (P less than 0.005) at ACH concentrations from 1 nM to 1 microM. Similarly, ACH (1 nM to 100 nM) induced less EA vasodilation in CsA rats (P less than 0.025). In control and CsA rats, the addition of nitro-L-arginine abolished AA and EA vasodilation induced by ACH, suggesting that the sustained vasodilatory responses of AA and EA to ACH are mainly dependent on nitric oxide synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)


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