Cristina Cartiglia - Academia.edu (original) (raw)

Papers by Cristina Cartiglia

Toxicology Mechanisms and Methods, 2003

Archives of Ophthalmology, Jun 1, 2010

To analyze the frequency of mitochondrial DNA (mtDNA) damage in patients with primary open-angle ... more To analyze the frequency of mitochondrial DNA (mtDNA) damage in patients with primary open-angle glaucoma. Oxidative damage plays a major role in glaucoma pathogenesis. Since no environmental risk factor for glaucoma is recognized, we focused our attention on mitochondria, the main endogenous source of reactive oxygen species. Methods: Mitochondrial damage was evaluated analyzing a common mtDNA deletion by real-time polymerase chain reaction in trabecular meshwork collected at surgery from 79 patients with primary open-angle glaucoma and 156 unaffected matched controls. In the same samples, polymorphisms of genes encoding for antioxidant defenses (GSTM1), repair of oxidative DNA damage (OGG1), and apoptosis (FAS) were tested. Results: Mitochondrial DNA deletion was dramatically increased (5.32-fold; P = .01) in trabecular meshwork of patients with glaucoma vs controls. This finding was paralleled by a decrease in the number of mitochondria per cell (4.83-fold; P Ͻ .001) and by cell loss (16.36-fold; P Ͻ .01). Patients with glaucoma bearing the GSTM1null genotype showed increased amounts of mtDNA deletion and a decreased number of mitochondria per cell as compared with GSTM1-positive subjects. Patients bearing a FAS homozygous mutation showed only a decreased number of mitochondria per cell. Conclusions: Obtained results indicate that mitochondrion is targeted by the glaucomatous pathogenic processes. Some subjects bearing adverse genetic assets are more susceptible to this event. Clinical Relevance: Oxidative damage to the trabecular meshwork exerts a pathogenic role in glaucoma inducing mitochondrial damage and triggering apoptosis and cell loss. This issue may be useful to develop new glaucoma molecular biomarkers and to identify highrisk subjects.

Journal of Proteome Research, Sep 3, 2010

ATPase, Na+/K+ transporting, beta 3 polypeptide A3KLL5 ↑ 2.8** Cell homeostasis Non-catalytic com... more ATPase, Na+/K+ transporting, beta 3 polypeptide A3KLL5 ↑ 2.8** Cell homeostasis Non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na+ and K+ ions across the plasma membrane. Membrane protein

The American Journal of Medicine, Jun 1, 2003

Free Radical Research, May 11, 2011

Oxidative damage plays a pathogenic role in various chronic degenerative diseases. Oxidative dama... more Oxidative damage plays a pathogenic role in various chronic degenerative diseases. Oxidative damage targeting trabecular meshwork (TM) cells as a consequence of mitochondrial damage is a pathogenic mechanism for glaucoma, the most common cause of irreversible blindness worldwide. Consequences of oxidative damage are attenuated by endocellular activities involved in scavenging reactive oxidative species and DNA repair. Selected bacterial genes are highly efficient at protecting cells from oxidative DNA damage. This situation occurs for Escherichia coli formamidopyrimidine DNA glycosylase (FPG), a major DNA glycosylase that repairs oxidatively damaged DNA. Accordingly, this study was aimed at transfecting human TM cells (HTMC) with Fpg in order to increase their resistance to oxidative damage. This study demonstrates that it is feasible to increase resistance of HTMC to endogenous oxidative damage by gene transfection. These findings bear relevance for primary and secondary prevention of degenerative glaucomas and other degenerative diseases where oxidative damage plays a pathogenic role.

Journal of Preventive Medicine and Hygiene, 2013

Summary Biphosphonate (BPN) are widely used in clinics to treat metastatic cancer and osteoporosi... more Summary Biphosphonate (BPN) are widely used in clinics to treat metastatic cancer and osteoporosis thus representing a problem not only for patients but also for workers involved in their preparation and administration. A similar exposure occurred years ago in match-making workers undergoing bone alterations similar to those consequent to BPN exposure. Osteonecrosis of the jaw (ONJ) is a main adverse effect related to BPN administration, which is performed in millions of patients worldwide for osteoporosis and cancer therapy, thus representing an emerging problem in public health. In susceptible patients, BPN induce severe, progressive, and irreversible degeneration of facial bones, resulting in avascular ONJ often triggered by dental surgery. BPN induced ONJ occurs in subjects depending on lifestyle factors of both environmental and endogenous origins. Exogenous risk factors include cigarette smoke, alcohol consumption, bacterial infections, and cyclosporine therapy. Endogenous ris...

Cancer research, 1999

7,12-Dimethylbenz(a)anthracene (DMBA) is a prototype carcinogen that induces a high yield of mamm... more 7,12-Dimethylbenz(a)anthracene (DMBA) is a prototype carcinogen that induces a high yield of mammary tumors in rats after a single feeding. We investigated the induction and chemoprevention of DNA adducts in female Sprague Dawley rats receiving DMBA by gavage according to a variety of treatment schedules. The patterns of 32P-postlabeled DNA adducts in liver and mammary epithelial cells were similar to those produced by the in vitro reaction of metabolically activated DMBA with calf thymus DNA. There was a high and statistically significant correlation between dose of DMBA administered to rats (0, 0.6, 2.4, and 12 mg/kg body weight) and levels of DNA adducts in both types of cells. The regression lines relating DMBA doses to total DNA adduct levels were significantly divergent and crossed at 1.5 mg/kg body weight, indicating that, at lower doses, the formation of DNA adducts is more intense in target mammary cells, whereas at higher doses, DNA adduct levels are more elevated in liver...

Handbook of Nutrition, Diet and the Eye, 2014

Abstract Glaucoma is a disease known since the time of Hippocrates. Today, the term glaucoma refe... more Abstract Glaucoma is a disease known since the time of Hippocrates. Today, the term glaucoma refers to a spectrum of neurodegenerative diseases that have in common progressive optical atrophy resulting from the apoptosis of retinal ganglion cells, and axonal atrophy and degeneration extending to the visual areas of the brain cortex, finally leading to the characteristic optical-cup neuropathy and irreversible visual loss. The action of many factors, including aging, genetic predisposition, exogenous environmental and endogenous factors, is necessary for the development of glaucoma. In addition to ganglion cell loss, most glaucoma types are characterized by high intraocular pressure. This is due to the damage that occurs in the trabecular meshwork, a key region in the pathogenesis of high-pressure glaucoma. In normal-pressure glaucoma, the pathogenesis is different, with vascular factors playing a very important role.

The FASEB Journal, 2004

We previously showed that sunlight-mimicking light induces genotoxic damage not only in skin but ... more We previously showed that sunlight-mimicking light induces genotoxic damage not only in skin but also even in lung, bone marrow, and peripheral blood of hairless mice. Moreover, light and smoke acted synergically in the respiratory tract. To clarify the mechanisms involved, we investigated by cDNA-arrays the expression of 746 toxicologically relevant genes in skin and lungs of mice exposed for 28 days to light and/or environmental cigarette smoke. Glutathione-S-transferase-Pi and catalase were overexpressed in the lungs of mice exposed to light only. Moreover, the light induced in skin the expression of genes involved in carcinogenesis, photoaging, and production of genotoxic and oxidizing derivatives traveling at a distance. Smoke induced the expression of multiple genes in both skin and lung, which reflect adaptive responses and mechanisms related to cancer and, possibly, to emphysema and stroke. As shown in mice exposed to both light and smoke, the light tended to increase smoke-induced gene expression in lungs, while smoke tended to attenuate light-induced gene expression in skin. The oral administration of the nonsteroidal anti-inflammatory drug sulindac inhibited the light-induced overexpression of cyclooxygenase-2 and oxidative stress-related genes in skin, and downregulated smoke-induced genes involved in oxidative stress, removal of damaged proteins, inflammation, and immune response in lung. These results provide a mechanistic insight explaining the systemic alterations induced by both light and smoke in mouse skin and lungs. Key words: environmental cigarette smoke • UV-containing light • multigene expression • cDNA array • hairless mice enomic and postgenomic methodologies have provided new formidable tools applicable to the study of a variety of biomedical issues, also including the comprehension of the mechanisms of toxic and carcinogenic agents and their modulation by pharmacological and dietary factors. UV-containing light and cigarette smoke are widespread toxic and carcinogenic agents. Collectively, they have been estimated to account for 40% of all human cancers (1). Although humans are generally exposed to both agents and several theoretical mechanisms by which light and smoke might reciprocally influence their biological effects are considered, their interaction G

PLoS ONE, 2011

Background: Trabecular meshwork and Schlemm's canal are the tissues appointed to modulate the aqu... more Background: Trabecular meshwork and Schlemm's canal are the tissues appointed to modulate the aqueous humour outflow from the anterior chamber. The impairment of their functions drives to an intraocular pressure increase. The selective laser trabeculoplasty is a laser therapy of the trabecular meshwork able to decrease intraocular pressure. The exact response mechanism to this treatment has not been clearly delineated yet. The herein presented study is aimed at studying the gene expression changes induced in trabecular meshwork cells by selective laser trabeculoplasty (SLT) in order to better understand the mechanisms subtending its efficacy. Methodology/Principal Findings: Primary human trabecular meshwork cells cultured in fibroblast medium underwent selective laser trabeculoplasty treatment. RNA was extracted from a pool of cells 30 minutes after treatment while the remaining cells were further cultured and RNA was extracted respectively 2 and 6 hours after treatment. Control cells stored in incubator in absence of SLT treatment were used as reference samples. Gene expression was evaluated by hybridization on miRNA-microarray and laser scanner analysis. Scanning electron microscopic examination was performed on 2 Trabecular meshwork samples after SLT at 4 th and 6 th hour from treatment. On the whole, selective laser trabeculoplasty modulates in trabecular meshwork the expression of genes involved in cell motility, intercellular connections, extracellular matrix production, protein repair, DNA repair, membrane repair, reactive oxygen species production, glutamate toxicity, antioxidant activities, and inflammation. Conclusions/Significance: SLT did not induce any phenotypic alteration in TM samples. TM is a complex tissue possessing a great variety of function pivotal for the active regulation of aqueous humour outflow from the anterior chamber. SLT is able to modulate these functions at the postgenomic molecular level without inducing damage either at molecular or phenotypic levels.

Neurology, 2008

BRAIN DAMAGE AS DETECTED BY CDNA-MICROARRAY IN THE SPINAL FLUID OF PATIENTS WITH AICARDI-GOUTIÈRE... more BRAIN DAMAGE AS DETECTED BY CDNA-MICROARRAY IN THE SPINAL FLUID OF PATIENTS WITH AICARDI-GOUTIÈRES SYNDROME Aicardi-Goutières syndrome (AGS) is a rare encephalopathy, arising during the first year of life, characterized by cerebral atrophy, leukodystrophy, basal ganglia calcification, raised interferon (IFN)-alpha in the CSF, CSF lymphocytosis, and negative serologic findings for infections. 1,2 Identification of AGS pathogenesis may provide insights into the neurodegenerative mechanism resulting from exposure of the developing human brain to IFN-alpha. The aim of this study is to provide an insight into global gene expression of CSF cells in AGS using microarray technology.

Mutation Research/Reviews in Mutation Research, 2012

MicroRNAs (miRNAs) have been implicated in many biological processes, cancer, and other diseases.... more MicroRNAs (miRNAs) have been implicated in many biological processes, cancer, and other diseases. In addition, miRNAs are dysregulated following exposure to toxic and genotoxic agents. Here we review studies evaluating modulation of miRNAs by dietary and pharmacological agents, which could potentially be exploited for inhibition of mutagenesis and carcinogenesis. This review covers natural agents, including vitamins, oligoelements, polyphenols, isoflavones, indoles, isothiocyanates, phospholipids, saponins, anthraquinones and polyunsaturated fatty acids, and synthetic agents, including thiols, nuclear receptor agonists, histone deacetylase inhibitors, antiinflammatory drugs, and selective estrogen receptor modulators. As many as 145 miRNAs, involved in the control of a variety of carcinogenesis mechanisms, were modulated by these agents, either individually or in combination. Most studies used cancer cells in vitro with the goal of modifying their phenotype by changing miRNA expression profiles. In vivo studies evaluated regulation of miRNAs by chemopreventive agents in organs of mice and rats, either untreated or exposed to carcinogens, with the objective of evaluating their safety and efficacy. The tissue specificity of miRNAs could be exploited for the chemoprevention of site-specific cancers, and the study of polymorphic miRNAs is expected to predict the individual response to chemopreventive agents as a tool for developing new prevention strategies.

Mutation Research/Reviews in Mutation Research, 2003

Birth is characterized by a sudden transition from the maternal-mediated respiration to the auton... more Birth is characterized by a sudden transition from the maternal-mediated respiration to the autonomous pulmonary respiration. Notwithstanding the importance of the involved functional and metabolic changes, little is known about possible DNA alterations occurring in the lung during the perinatal period. We comparatively evaluated genomic and transcriptional changes in the lung of fetuses and newborn Swiss albino mice, whose dams had either been untreated or treated with oral N-acetyl-L-cysteine (NAC) throughout the pregnancy period. In the less than 24h period elapsing between the end of fetal life and the start of post-natal life, nucleotide alterations occurred in mouse lung, as shown by a significant increase of both bulky DNA adducts and 8-hydroxy-2&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-deoxyguanosine levels, detected by 32P post-labeling procedures. The frequency of micronuclei in peripheral blood erythrocytes was not significantly increased after birth. Multigene expression analysis of 746 selected genes, by cDNA arrays, showed that 33 of them (4.4%) were upregulated in the lung of newborn mice, as compared with fetuses. The overexpressed genes were mainly involved in protective mechanism as a response to oxidative changes, alterations of glutathione metabolism, cellular stress, and damage to DNA and proteins. The transplacental treatment with NAC totally prevented birth-related genomic alterations in lung DNA. NAC did not change the basal gene expression in mouse fetal lung, but attenuated the upregulation of most genes involved in oxidative stress, stress response, and DNA repair in the lung of newborn mice. In fact, only 13 genes (1.7%) were overexpressed in newborns from NAC-treated dams. It therefore appears that administration of NAC during pregnancy is beneficial not only to counteract the adverse effects of toxic agents, as supported by previous studies, but also to attenuate birth-related DNA alterations.

Journal of Proteome Research, 2010

Investigative Opthalmology & Visual Science, 2009

PURPOSE. The anterior chamber of the eye is a highly specialized structure delimited by the corne... more PURPOSE. The anterior chamber of the eye is a highly specialized structure delimited by the cornea, lens, and iris. It contains the aqueous humor, secreted by the ciliary body and drained by the trabecular meshwork. Alteration of aqueous humor homeostasis plays a major role in the pathogenesis of glaucoma. The trabecular meshwork is the target tissue of glaucoma in the anterior chamber, and the development and progression of glaucoma are accompanied by accumulation of oxidative damage in this tissue. This study was conducted to comparatively evaluate the sensitivity to oxidative stress of anterior chamber tissues including the cornea, iris, and trabecular meshwork. METHODS. Cornea, iris, and trabecular meshwork fragments collected from six cornea donors were either left untreated or treated with hydrogen peroxide. Oxidative damage was determined by evaluating nucleotide oxidative modifications (8hydroxy-2Ј-deoxyguanosine) and apurinic alkali-fragile sites by capillary electrophoresis. RESULTS. The results indicated that the basal level of oxidative nucleotide modifications was higher in the cornea than in the iris and trabecular meshwork. The trabecular meshwork was the most sensitive tissue to oxidative damage, as after exposure to hydrogen peroxide both markers of oxidative damage dramatically increased in the trabecular meshwork but not in the cornea and iris. CONCLUSIONS. Because the cornea and iris are directly exposed to light, they possess antioxidant defense mechanisms that are not activated in the trabecular meshwork. The peculiar sensitivity of the trabecular meshwork to oxidative stress is consistent with the damage selectively induced in it, triggering glaucoma's pathogenic cascade.

International Journal of Cancer, 2012

Dysregulation of microRNAs (miRNAs) has important consequences on gene and protein expression sin... more Dysregulation of microRNAs (miRNAs) has important consequences on gene and protein expression since a single miRNA targets a number of genes simultaneously. This article provides a review of published data and ongoing studies regarding the effects of cigarette smoke (CS), either mainstream (MCS) or environmental (ECS), on the expression of miRNAs and related proteins. The results generated in mice, rats, and humans provided evidence that exposure to CS results in an intense dysregulation of miRNA expression in the respiratory tract, which is mainly oriented in the sense of downregulation. In parallel, there was an upregulation of proteins targeted by the downregulated miRNAs. These trends reflect an attempt to defend the respiratory tract by means of antioxidant mechanisms, detoxification of carcinogens, DNA repair, anti-inflammatory pathways, apoptosis, etc. However, a long-lasting exposure to CS causes irreversible miRNA alterations that activate carcinogenic mechanisms, such as modulation of oncogenes and oncosuppressor genes, cell proliferation, recruitment of undifferentiated stem cells, inflammation, inhibition of intercellular communications, angiogenesis, invasion, and metastasis. The miRNA alterations induced by CS in the lung of mice and rats are similar to those observed in the human respiratory tract. Since a number of miRNAs that are modulated by CS and/or chemopreventive agents are subjected to single nucleotide polymorphisms in humans, they can be evaluated according to toxicogenomic/pharmacogenomics approaches. A variety of cancer chemopreventive agents tested in our laboratory modulated both baseline and CS-related miRNA and proteome alterations, thus contributing to evaluate both safety and efficacy of dietary and pharmacological agents.

Implant Dentistry, 2011

This study aims at applying cDNA microarray analysis in vitro for establishing and comparing the ... more This study aims at applying cDNA microarray analysis in vitro for establishing and comparing the osteogenic properties of dental implants with different surface characteristics. Materials and Methods: Saos-2 osteoblasts were cultured in bottomcone tubes in presence of 5 different dental implants with various surface characteristics. Cells adherent to dental implants were detached and RNA purified. The expression of 18,401 genes was tested by cDNA microarray. Results: The number and viability of cells adherent to different dental implants varied but without any significant statistical difference. Conversely, gene expression was revealed to be a more sensitive biomarker being remarkably different in cells adherent to different implants. The 5 dental implants significantly modulated the expression of 14 osteogenic activities mainly including bone morphogenetic proteins, osteomodulin, and osteoprotegerin. Conclusion: Despite no significant differences having been found in in vitro cell number and viability, cells adherent to 5 differently surfaced implants showed different gene expression profiles. Thus, to evaluate osteogenesis as related to dental implants, it is important to analyze not only the number of adherent cells but also the activation of genes encoding for osteogenic activities.

Free Radical Research, 2011

Carcinogenesis, 2006

Infection by Helicobacter pylori is the most important risk factor for gastric cancer. However, o... more Infection by Helicobacter pylori is the most important risk factor for gastric cancer. However, only a small fraction of colonized individuals, representing at least half of the world's population, develop this malignancy. In order to shed light on host-microbial interactions, gastric mucosa biopsies were collected from 119 patients suffering from dyspeptic symptoms. 8-Hydroxy-2 0-deoxyguanosine (8-oxo-dG) levels in the gastric mucosa were increased in carriers of H.pylori, detected either by cultural method or by polymerase chain reaction, and were further increased in subjects infected with strains positive for the cagA gene, encoding the cytotoxin-associated protein, cagA. Oxidative DNA damage was more pronounced in males, in older subjects, and in H.pylori-positive subjects suffering from gastric dysplasia. Moreover, 8-oxo-dG levels were significantly higher in a small subset of subjects having a homozygous variant allele of the 8-oxoguanosine-glycosylase 1 (OGG1) gene, encoding the enzyme removing 8oxo-dG from DNA. Conversely, they were not significantly elevated in glutathione S-transferase M1 (GSTM1)-null subjects. Thus, both bacterial and host gene polymorphisms affect oxidative stress and DNA damage, which is believed to represent a key mechanism in the pathogenesis of gastric cancer. The interplay between bacterial and host gene polymorphisms may explain why gastric cancer only occurs in a small fraction of H.pylori-infected individuals.