Publications (48) View all
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Article: Peritoneal dialysis fluid activates calcium signaling and apoptosis in mesothelial cells.
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ABSTRACT: A larger diffusion of peritoneal dialysis (PD) is limited by the progressive deterioration of the dialysis membrane structure and function, characterized in vitro and in vivo by mesothelial cell loss and closely related to the use of bioincompatible dialysis solutions. The apoptosis rate of rat and human mesothelial cells incubated in commercial PD fluid (PDF, 4.25 g/dL dextrose) became significant as early as 1 h after PDF addition and reached a plateau at 4-5 h. This pattern was unchanged after exposure to 1.5 g/dL dextrose PDF or freshly prepared PDF, indicating that effects were independent on the dextrose strength and manufacturing procedures but strictly dependent on PDF composition. Molecular studies revealed that PDF exposure inactivated the physiological volume recovery from hypertonic shrinkage, accompanied by an abnormal Ca(2+) signaling: a progressive intracellular Ca(2+) ([Ca(2+)](i)) rise resulting from an increased Ca(2+) entry. PDF also affected cytoskeleton integrity: early dissolution of actin filaments occurred well before the appearance of typical apoptosis features. Lastly, the PDF dependent apoptosis was almost completely prevented by the contemporary Ca(2+) concentration decrease and K(+) addition. This study suggests that the PDF dependent apoptosis arises from the extreme volume perturbations in mesothelial cells, turned out unable to regulate their volume back once exposed to a hyperosmolal medium containing high Ca(2+) levels in the absence of K(+), such PDF.Apoptosis 10/2012; · 4.07 Impact Factor -
Article: Effect of Annurca Apple Polyphenols on Human HaCaT Keratinocytes Proliferation.
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ABSTRACT: Abstract Polyphenols have been demonstrated to have clear antioxidant activities in vitro. However, in complex biological systems, they exhibit additional properties, which are yet poorly understood. The apple is among the most consumed fruits worldwide, and several studies suggest that apple polyphenols could play a role in the prevention of degenerative diseases. The present study aimed at evaluating the Annurca apple polyphenol extract (APE) effects both proliferation and apoptosis on HaCaT cells. The data indicate that apple polyphenolic compounds had significant antiproliferative action on HaCaT cells. The fluorescence-activated cell-sorting analysis showed that APE induced cell apoptosis in a dose-dependent manner. Moreover, apple polyphenols induced apoptosis in epithelial cells by triggering a death receptor-associated extrinsic pathway p53-independent. APE was also capable of inducing morphological changes as evidenced by nuclear condensation. The cellular, morphological, and molecular data unequivocally demonstrated that induction of cellular apoptosis was mainly responsible for the previously observed antiproliferation-induced APE on HaCaT keratinocytes. Our experimental results suggest that apple polyphenols are a promising source from which a natural-based topical agent could be developed for skin diseases treatment.Journal of medicinal food 08/2012; · 1.39 Impact Factor -
Article: Epirubicin permeation of personal protective equipment can induce apoptosis in keratinocytes.
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ABSTRACT: The present study investigated the epirubicin (EPI) permeability of various commercially available glove types, as well as toxicity mechanisms and effects on human keratinocyte cell line (HaCaT). Permeability experiments were carried out on various commercially available gloves, differing as regards material and thickness. Permeability was evaluated after different "contact times" and the influence of EPI solution's pH (acid and neutral) on permeability was also examined. Toxicity of EPI toward skin was tested by evaluating the effects of the drug on cell growth and apoptosis, by using an in vitro model based on cultured immortalized human keratinocytes. No permeation was detected in the case of EPI neutral solutions; in contrast, acid solutions were found to penetrate low thickness nitrile gloves. Obtained results also showed the induction of apoptosis in epithelial cells through the activation of intrinsic pathway p53-independent occurring even when cells are exposed at low drug concentration. EPI solution's pH influences the glove's permeability; once penetrated, EPI at concentrations lower than those able to penetrate the nitrile glove during the 8-h work-shift can cause apoptosis in epithelial cells. The findings reported here highly support the choice of either natural rubbers gloves or high thickness nitrile ones for preventing the occupational exposure to EPI.Journal of Exposure Science and Environmental Epidemiology advance online publication, 9 May 2012; doi:10.1038/jes.2012.38.Journal of Exposure Science and Environmental Epidemiology 05/2012; · 2.93 Impact Factor -
Article: In vitro model of stromal and epithelial immortalized endometriotic cells.
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ABSTRACT: Endometriosis is a relatively common chronic gynecologic disorder that usually presents with chronic pelvic pain or infertility. It results from implantation of endometrial tissue outside the uterine cavity. Despite its frequency and its impact on quality of life, the understanding of pathogenesis of endometriosis remains incomplete and its treatment remains controversial. In this work, we established a suitable in vitro model system of immortalized human endometriotic cell line taking advantage of the human telomerase reverse transcriptase. The results demonstrate that these cells retain the natural characteristics of endometrial cells in term of phenotype and of functional expression of estrogen and progesterone receptors, without chromosomal abnormalities. In conclusion, these cells are potentially useful as an experimental model to investigate endometriosis biology.Journal of Cellular Biochemistry 11/2011; 113(4):1292-301. · 2.87 Impact Factor -
Article: Altered oxido-reductive state in the diabetic heart: loss of cardioprotection due to protein disulfide isomerase.
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ABSTRACT: Diabetes is associated with an increased risk of heart failure, in part explained by endoplasmic reticulum stress and apoptosis. Protein disulfide isomerase (PDI) prevents stressed cardiomyocytes apoptosis. We hypothesized that diabetes impairs PDI function by an alteration in its oxido-reductive state. Myocardial biopsies harvested from the anterolateral left ventricular wall from diabetic (n = 7) and nondiabetic (n = 8) patients were used to assess PDI expression and cardiomyocyte death. A mouse model of diabetes (streptozotocin injection, 130 mg/mL) was used to study PDI expression and its redox state after ischemia/reperfusion injury induced by 30-min occlusion of the left anterior coronary artery followed by reperfusion. Transthoracic echocardiography was performed to assess cardiac remodeling after 1 wk. Western blot analysis was used to analyze PDI expression, and methoxy-polyethyleneglycol-maleimide was used to assess its redox state. Dehydroascorbate (DHA) administration was used to restore the PDI redox state. Diabetic patients had a greater number of transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells than nondiabetic patients despite a greater myocardial PDI expression suggesting altered PDI function. Diabetic mice had a worse postinfarction remodeling associated with an altered PDI redox state. DHA treatment restored functional PDI redox state and ameliorated post-myocardial infarction remodeling. An increase in PDI levels with a paradoxical decrease of its active form occurs in the diabetic heart after ischemia and may explain the lack of protective effects of PDI in diabetes. Restoration of PDI redox state prevents adverse remodeling. The potential significance of these findings deserves to be validated in a clinical setting.Molecular Medicine 05/2011; 17(9-10):1012-21. · 3.76 Impact Factor
