Effect of silver nanoparticles upon the myocardial and coronary vascular function in isolated and perfused diabetic rat hearts.

Silver nanoparticles (AgNPs) are promising antibacterial nanomaterials for diagnostic and treatment of diabetes. However, toxicity and adverse cardiac responses induced by AgNPs related to nitric oxide (NO) and oxidative stress (OS) are described. Moreover, little is known about the diabetes influence upon AgNPs-toxicity. The aim of this work was to evaluate cardiovascular function in response to AgNPs through measuring perfusion pressure (PP) and left ventricle pressure (LVP), using perfused hearts from streptozotocin (STZ)-induced diabetic rats and identify the role of NO and OS. High concentrations but not the lower concentrations of AgNPs, promotes increases in PP and LVP, as well as increased OS. Additionally, diabetes alters the classic effects of phenylephrine (Phe) and acetylcholine (ACh). These data suggest that diabetes may intensify AgNPs-cardiotoxicity. Nevertheless, the precise mechanism of action is still under elucidation.

SerpinA3g participates in the antiadipogenesis and insulin-resistance induced by tumor necrosis factor-α in 3T3-F442A cells.

Tumor necrosis factor alpha (TNF-α) is a proven modulator of adipose metabolism, but the mechanisms by which this cytokine affects the development and function of adipose tissue have not been fully elucidated to date. Using differential display analysis, in this study, we demonstrate that gene expression of the serine protease inhibitor A3g (SerpinA3g) is specifically induced in 3T3-F442A preadipocytes by TNF-α but not by other adipogenic inhibitors, such as retinoic acid (RA) or transforming growth factor type beta (TGF-ß). The specific induction of SerpinA3g by TNF-α was confirmed by RT-PCR in both preadipose and terminally differentiated 3T3-F442A cells. The knockdown of SerpinA3g using small interfering RNA prevented the antiadipogenesis elicited by TNF-α in 3T3-F442A cells but not the antiadipogenesis induced by RA or TGF-ß. SerpinA3g-silenced 3T3-F442A cells also did not display TNF-α-induced insulin resistance. Our results demonstrate that SerpinA3g is specifically induced by TNF-α in 3T3-F442A cells, regardless of their stage of differentiation, and participates in the antiadipogenesis and insulin resistance induced by this cytokine. Our results suggest that SerpinA3g plays a role in the TNF-α modulation of adipose tissue development and metabolism. Additional studies are warranted regarding the mechanisms mediating adipose SerpinA3g effects.

The 1.3 isoform of Na+–Ca2+ exchanger expressed in guinea pig tracheal smooth muscle is less sensitive to KB-R7943

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The sodium–calcium exchanger (NCX) plays a major role in the regulation of cytosolic Ca2+ in muscle cells. In this work, we performed force experiments to explore the role of NCX during contraction and relaxation of Cch-stimulated guinea pig tracheal smooth muscle strips. This tissue showed low sensitivity to NCX inhibitor KB-R7943 (IC50, 57 ± 2 µM), although a complete relaxation was obtained by NCX inhibition at 100 µM. Interestingly, relaxation after washing the agonist was prolonged in the absence of external Na+, whereas washing without Na+ and in the presence of KB-R7943 resembled control conditions with physiological solution. Altogether, this suggests the reversal of NCX to a Ca2+ influx mode by the manipulation on the Na+ gradient, which can be inhibited by KB-R7943. In order to understand the low sensitivity to KB-R7943, we studied the molecular aspects of the NCX expressed in this tissue and found that the isoform of NCX expressed is 1.3, similar to that described in human tracheal smooth muscle. Sequencing revealed that amino acid 19 in exon B is phenylalanine, whereas in its human counterpart is leucine, and that the first amino acid after exon D is aspartate instead of glutamate in humans. Results herein presented are discussed in term of their possible functional implications in the exchanger activity and thus in airway physiology (AU)

The 1.3 isoform of Na+-Ca 2+ exchanger expressed in guinea pig tracheal smooth muscle is less sensitive to KB-R7943.

The sodium-calcium exchanger (NCX) plays a major role in the regulation of cytosolic Ca(2+) in muscle cells. In this work, we performed force experiments to explore the role of NCX during contraction and relaxation of Cch-stimulated guinea pig tracheal smooth muscle strips. This tissue showed low sensitivity to NCX inhibitor KB-R7943 (IC50, 57 +/- 2 microM), although a complete relaxation was obtained by NCX inhibition at 100 microM. Interestingly, relaxation after washing the agonist was prolonged in the absence of external Na(+), whereas washing without Na(+) and in the presence of KB-R7943 resembled control conditions with physiological solution. Altogether, this suggests the reversal of NCX to a Ca(2+) influx mode by the manipulation on the Na(+) gradient, which can be inhibited by KB-R7943. In order to understand the low sensitivity to KB-R7943, we studied the molecular aspects of the NCX expressed in this tissue and found that the isoform of NCX expressed is 1.3, similar to that described in human tracheal smooth muscle. Sequencing revealed that amino acid 19 in exon B is phenylalanine, whereas in its human counterpart is leucine, and that the first amino acid after exon D is aspartate instead of glutamate in humans. Results herein presented are discussed in term of their possible functional implications in the exchanger activity and thus in airway physiology.