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Article ; Online: The Critical Impact of Sphingolipid Metabolism in Breast Cancer Progression and Drug Response

Paola Antonia Corsetto / Stefania Zava / Angela Maria Rizzo / Irma Colombo

International Journal of Molecular Sciences, Vol 24, Iss 2107, p

2023 Volume 2107

Abstract: Breast cancer is the second leading cause of cancer-related death in women in the world, and its management includes a combination of surgery, radiation therapy, chemotherapy, and immunotherapy, whose effectiveness depends largely, but not exclusively, ... ...

Abstract	Breast cancer is the second leading cause of cancer-related death in women in the world, and its management includes a combination of surgery, radiation therapy, chemotherapy, and immunotherapy, whose effectiveness depends largely, but not exclusively, on the molecular subtype (Luminal A, Luminal B, HER2+ and Triple Negative). All breast cancer subtypes are accompanied by peculiar and substantial changes in sphingolipid metabolism. Alterations in sphingolipid metabolite levels, such as ceramides, dihydroceramide, sphingosine, sphingosine-1-phosphate, and sphingomyelin, as well as in their biosynthetic and catabolic enzymatic pathways, have emerged as molecular mechanisms by which breast cancer cells grow, respond to or escape therapeutic interventions and could take on diagnostic and prognostic value. In this review, we summarize the current landscape around two main themes: 1. sphingolipid metabolites, enzymes and transport proteins that have been found dysregulated in human breast cancer cells and/or tissues; 2. sphingolipid-driven mechanisms that allow breast cancer cells to respond to or evade therapies. Having a complete picture of the impact of the sphingolipid metabolism in the development and progression of breast cancer may provide an effective means to improve and personalize treatments and reduce associated drug resistance.
Keywords	breast cancer ; sphingolipids ; lipids ; metabolism ; ceramide ; sphingomyelin ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610 ; 616
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Exogenous Fatty Acids Modulate ER Lipid Composition and Metabolism in Breast Cancer Cells

Angela Maria Rizzo / Irma Colombo / Gigliola Montorfano / Stefania Zava / Paola Antonia Corsetto

Cells, Vol 10, Iss 175, p

2021 Volume 175

Abstract: 1) Background: Lipid metabolism is a fundamental hallmark of all tumors, especially of breast cancer. Few studies describe the different lipid metabolisms and sensitivities to the microenvironment of breast cancer cell subtypes that influence the ... ...

Abstract	(1) Background: Lipid metabolism is a fundamental hallmark of all tumors, especially of breast cancer. Few studies describe the different lipid metabolisms and sensitivities to the microenvironment of breast cancer cell subtypes that influence the proliferation, aggressiveness, and success of therapy. This study describes the impact of lipid microenvironment on endoplasmic reticulum (ER) membrane and metabolic activity in two breast cancer cell lines with Luminal A and triple-negative breast cancer (TNBC) features. (2) Methods: We investigated the peculiar lipid phenotype of a TNBC cell line, MDA-MB-231, and a Luminal A cell line, MCF7, and their different sensitivity to exogenous fatty acids (i.e., palmitic acid (PA) and docosahexaenoic acid (DHA)). Moreover, we verified the impact of exogenous fatty acids on ER lipid composition. (3) Results: The data obtained demonstrate that MDA-MB-231 cells are more sensitive to the lipid microenvironment and that both PA and DHA are able to remodel their ER membranes with consequences on resident enzyme activity. On the contrary, MCF7 cells are less sensitive to PA, whereas they incorporate DHA, although less efficiently than MDA-MB-231 cells. (4) Conclusions: This study sustains the importance of lipid metabolism as an innovative hallmark to discriminate breast cancer subclasses and to develop personalized and innovative pharmacological strategies. The different sensitivities to the lipid environment shown by MCF7 and MDA-MB-231 cells might be related to cell malignancy and chemoresistance onset. In the future, this new approach could lead to a substantial decrease both in deleterious side effects for the patients and in the cost of entire therapeutic treatments coupled with increased therapy efficiency.
Keywords	lipid metabolism ; cancer ; ER ; fatty acids ; Biology (General) ; QH301-705.5
Subject code	616
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Antioxidant Response during the Kinetics of Anhydrobiosis in Two Eutardigrade Species

Ilaria Giovannini / Paola Antonia Corsetto / Tiziana Altiero / Gigliola Montorfano / Roberto Guidetti / Angela Maria Rizzo / Lorena Rebecchi

Life, Vol 12, Iss 817, p

2022 Volume 817

Abstract: Anhydrobiosis, a peculiar adaptive strategy existing in nature, is a reversible capability of organisms to tolerate a severe loss of their body water when their surrounding habitat is drying out. In the anhydrobiotic state, an organism lacks all dynamic ... ...

Abstract	Anhydrobiosis, a peculiar adaptive strategy existing in nature, is a reversible capability of organisms to tolerate a severe loss of their body water when their surrounding habitat is drying out. In the anhydrobiotic state, an organism lacks all dynamic features of living beings since an ongoing metabolism is absent. The depletion of water in the anhydrobiotic state increases the ionic concentration and the production of reactive oxygen species (ROS). An imbalance between the increased production of ROS and the limited action of antioxidant defences is a source of biomolecular damage and can lead to oxidative stress. The deleterious effects of oxidative stress were demonstrated in anhydrobiotic unicellular and multicellular organisms, which counteract the effects using efficient antioxidant machinery, mainly represented by ROS scavenger enzymes. To gain insights into the dynamics of antioxidant patterns during the kinetics of the anhydrobiosis of two tardigrade species, Paramacrobiotus spatialis and Acutuncus antarcticus , we investigated the activity of enzymatic antioxidants (catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase) and the amount of non-enzymatic antioxidants (glutathione) in the course of rehydration. In P. spatialis , the activity of catalase increases during dehydration and decreases during rehydration, whereas in A. antarcticus , the activity of superoxide dismutase decreases during desiccation and increases during rehydration. Genomic varieties, different habitats and geographical regions, different diets, and diverse evolutionary lineages may have led to the specialization of antioxidant strategies in the two species.
Keywords	anhydrobiosis ; desiccation stress ; ROS ; scavenging enzymes ; tardigrades ; Science ; Q
Subject code	580
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: LSEA Evaluation of Lipid Mediators of Inflammation in Lung and Cortex of Mice Exposed to Diesel Air Pollution

Luca Massimino / Alessandra Bulbarelli / Paola Antonia Corsetto / Chiara Milani / Laura Botto / Francesca Farina / Luigi Antonio Lamparelli / Elena Lonati / Federica Ungaro / Krishna Rao Maddipati / Paola Palestini / Angela Maria Rizzo

Biomedicines, Vol 10, Iss 3, p

2022 Volume 712

Abstract: Airborne ultrafine particle (UFP) exposure is a great concern as they have been correlated to increased cardiovascular mortality, neurodegenerative diseases and morbidity in occupational and environmental settings. The ultrafine components of diesel ... ...

Abstract	Airborne ultrafine particle (UFP) exposure is a great concern as they have been correlated to increased cardiovascular mortality, neurodegenerative diseases and morbidity in occupational and environmental settings. The ultrafine components of diesel exhaust particles (DEPs) represent about 25% of the emission mass; these particles have a great surface area and consequently high capacity to adsorb toxic molecules, then transported throughout the body. Previous in-vivo studies indicated that DEP exposure increases pro- and antioxidant protein levels and activates inflammatory response both in respiratory and cardiovascular systems. In cells, DEPs can cause additional reactive oxygen species (ROS) production, which attacks surrounding molecules, such as lipids. The cell membrane provides lipid mediators (LMs) that modulate cell-cell communication, inflammation, and resolution processes, suggesting the importance of understanding lipid modifications induced by DEPs. In this study, with a lipidomic approach, we evaluated in the mouse lung and cortex how DEP acute and subacute treatments impact polyunsaturated fatty acid-derived LMs. To analyze the data, we designed an ad hoc bioinformatic pipeline to evaluate the functional enrichment of lipid sets belonging to the specific biological processes (Lipid Set Enrichment Analysis-LSEA). Moreover, the data obtained correlate tissue LMs and proteins associated with inflammatory process (COX-2, MPO), oxidative stress (HO-1, iNOS, and Hsp70), involved in the activation of many xenobiotics as well as PAH metabolism (Cyp1B1), suggesting a crucial role of lipids in the process of DEP-induced tissue damage.
Keywords	LSEA ; lipid mediators ; air pollution ; inflammation ; diesel exhaust particles ; Biology (General) ; QH301-705.5
Subject code	571
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Effect of Unloading Condition on the Healing Process and Effectiveness of Platelet Rich Plasma as a Countermeasure

Francesca Cialdai / Alessandra Colciago / Desiré Pantalone / Angela Maria Rizzo / Stefania Zava / Lucia Morbidelli / Fabio Celotti / Daniele Bani / Monica Monici

International Journal of Molecular Sciences, Vol 21, Iss 2, p

Study on In Vivo and In Vitro Wound Healing Models

2020 Volume 407

Abstract: Wound healing is a very complex process that allows organisms to survive injuries. It is strictly regulated by a number of biochemical and physical factors, mechanical forces included. Studying wound healing in space is interesting for two main reasons: ( ...

Abstract	Wound healing is a very complex process that allows organisms to survive injuries. It is strictly regulated by a number of biochemical and physical factors, mechanical forces included. Studying wound healing in space is interesting for two main reasons: (i) defining tools, procedures, and protocols to manage serious wounds and burns eventually occurring in future long-lasting space exploration missions, without the possibility of timely medical evacuation to Earth; (ii) understanding the role of gravity and mechanical factors in the healing process and scarring, thus contributing to unravelling the mechanisms underlying the switching between perfect regeneration and imperfect repair with scarring. In the study presented here, a new in vivo sutured wound healing model in the leech ( Hirudo medicinalis ) has been used to evaluate the effect of unloading conditions on the healing process and the effectiveness of platelet rich plasma (PRP) as a countermeasure. The results reveal that microgravity caused a healing delay and structural alterations in the repair tissue, which were prevented by PRP treatment. Moreover, investigating the effects of microgravity and PRP on an in vitro wound healing model, it was found that PRP is able to counteract the microgravity-induced impairment in fibroblast migration to the wound site. This could be one of the mechanisms underlying the effectiveness of PRP in preventing healing impairment in unloading conditions.
Keywords	wound healing ; hirudo medicinalis ; platelet rich plasma ; microgravity ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Omega-3 PUFA Loaded in Resveratrol-Based Solid Lipid Nanoparticles

Simona Serini / Roberta Cassano / Paola Antonia Corsetto / Angela Maria Rizzo / Gabriella Calviello / Sonia Trombino

International Journal of Molecular Sciences, Vol 19, Iss 2, p

Physicochemical Properties and Antineoplastic Activities in Human Colorectal Cancer Cells In Vitro

2018 Volume 586

Abstract: New strategies are being investigated to ameliorate the efficacy and reduce the toxicity of the drugs currently used in colorectal cancer (CRC), one of the most common malignancies in the Western world. Data have been accumulated demonstrating that the ... ...

Abstract	New strategies are being investigated to ameliorate the efficacy and reduce the toxicity of the drugs currently used in colorectal cancer (CRC), one of the most common malignancies in the Western world. Data have been accumulated demonstrating that the antineoplastic therapies with either conventional or single-targeted drugs could take advantage from a combined treatment with omega-3 polyunsaturated fatty acids (omega-3 PUFA). These nutrients, shown to be safe at the dosage generally used in human trials, are able to modulate molecules involved in colon cancer cell growth and survival. They have also the potential to act against inflammation, which plays a critical role in CRC development, and to increase the anti-cancer immune response. In the present study, omega-3 PUFA were encapsulated in solid lipid nanoparticles (SLN) having a lipid matrix containing resveratrol esterified to stearic acid. Our aim was to increase the efficiency of the incorporation of these fatty acids into the cells and prevent their peroxidation and degradation. The Resveratrol-based SLN were characterized and investigated for their antioxidant activity. It was observed that the encapsulation of omega-3 PUFA into the SLN enhanced significantly their incorporation in human HT-29 CRC cells in vitro, and their growth inhibitory effects in these cancer cells, mainly by reducing cell proliferation.
Keywords	colon cancer cells ; delivery ; encapsulation ; nanoparticles ; omega-3 ; resveratrol ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2018-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Enterocyte superoxide dismutase 2 deletion drives obesity

Oihane Garcia-Irigoyen / Fabiola Bovenga / Marilidia Piglionica / Elena Piccinin / Marica Cariello / Maria Arconzo / Claudia Peres / Paola Antonia Corsetto / Angela Maria Rizzo / Marta Ballanti / Rossella Menghini / Geltrude Mingrone / Philippe Lefebvre / Bart Staels / Takuji Shirasawa / Carlo Sabbà / Gaetano Villani / Massimo Federici / Antonio Moschetta

iScience, Vol 25, Iss 1, Pp 103707- (2022)

2022

Abstract: Summary: Compelling evidence support an involvement of oxidative stress and intestinal inflammation as early events in the predisposition and development of obesity and its related comorbidities. Here, we show that deficiency of the major mitochondrial ... ...

Abstract	Summary: Compelling evidence support an involvement of oxidative stress and intestinal inflammation as early events in the predisposition and development of obesity and its related comorbidities. Here, we show that deficiency of the major mitochondrial antioxidant enzyme superoxide dismutase 2 (SOD2) in the gastrointestinal tract drives spontaneous obesity. Intestinal epithelium-specific Sod2 ablation in mice induced adiposity and inflammation via phospholipase A2 (PLA2) activation and increased release of omega-6 polyunsaturated fatty acid arachidonic acid. Remarkably, this obese phenotype was rescued when fed an essential fatty acid-deficient diet, which abrogates de novo biosynthesis of arachidonic acid. Data from clinical samples revealed that the negative correlation between intestinal Sod2 mRNA levels and obesity features appears to be conserved between mice and humans. Collectively, our findings suggest a role of intestinal Sod2 levels, PLA2 activity, and arachidonic acid in obesity presenting new potential targets of therapeutic interest in the context of this metabolic disorder.
Keywords	Obesity medicine ; Lipid ; Molecular physiology ; Science ; Q
Subject code	610
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Space Flight Effects on Antioxidant Molecules in Dry Tardigrades

Angela Maria Rizzo / Tiziana Altiero / Paola Antonia Corsetto / Gigliola Montorfano / Roberto Guidetti / Lorena Rebecchi

BioMed Research International, Vol

The TARDIKISS Experiment

2015 Volume 2015

Abstract: The TARDIKISS (Tardigrades in Space) experiment was part of the Biokon in Space (BIOKIS) payload, a set of multidisciplinary experiments performed during the DAMA (Dark Matter) mission organized by Italian Space Agency and Italian Air Force in 2011. This ...

Abstract	The TARDIKISS (Tardigrades in Space) experiment was part of the Biokon in Space (BIOKIS) payload, a set of multidisciplinary experiments performed during the DAMA (Dark Matter) mission organized by Italian Space Agency and Italian Air Force in 2011. This mission supported the execution of experiments in short duration (16 days) taking the advantage of the microgravity environment on board of the Space Shuttle Endeavour (its last mission STS-134) docked to the International Space Station. TARDIKISS was composed of three sample sets: one flight sample and two ground control samples. These samples provided the biological material used to test as space stressors, including microgravity, affected animal survivability, life cycle, DNA integrity, and pathways of molecules working as antioxidants. In this paper we compared the molecular pathways of some antioxidant molecules, thiobarbituric acid reactive substances, and fatty acid composition between flight and control samples in two tardigrade species, namely, Paramacrobiotus richtersi and Ramazzottius oberhaeuseri. In both species, the activities of ROS scavenging enzymes, the total content of glutathione, and the fatty acids composition between flight and control samples showed few significant differences. TARDIKISS experiment, together with a previous space experiment (TARSE), further confirms that both desiccated and hydrated tardigrades represent useful animal tool for space research.
Keywords	Medicine ; R
Language	English
Publishing date	2015-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Lipid Reshaping and Lipophagy Are Induced in a Modeled Ischemia-Reperfusion Injury of Blood Brain Barrier

Elena Lonati / Paola Antonia Corsetto / Gigliola Montorfano / Stefania Zava / Tatiana Carrozzini / Anna Brambilla / Laura Botto / Paola Palestini / Angela Maria Rizzo / Alessandra Bulbarelli

International Journal of Molecular Sciences, Vol 20, Iss 15, p

2019 Volume 3752

Abstract: Ischemic-reperfusion (I/R) injury induced a remodeling of protein and lipid homeostasis, under oxidative stress and inflammatory status. Starvation occurring during I/R is a condition leading to autophagy activation, which allows abnormal material ... ...

Abstract	Ischemic-reperfusion (I/R) injury induced a remodeling of protein and lipid homeostasis, under oxidative stress and inflammatory status. Starvation occurring during I/R is a condition leading to autophagy activation, which allows abnormal material clearance or amino acid, or both, and fatty acid (FA) recycling essential for survival. This study investigated the lipid reshaping, peroxidation, and related-signaling pathways, in rat brain endothelial cells (RBE4) subjected to 3 h of oxygen and glucose deprivation (OGD) and restoration of standard condition (I/R in vitro model). Lipids and proteins were analyzed after 1 or 24 h of oxygen and nutrient restoration. Together with the oxidative stress and inflammatory status, I/R injury induced a reshaping of neutral lipids and biogenesis of lipid droplets (LD) with excessive lipid storage. The increase of LC3-II/LC3-I ratio, an autophagy marker, and LC3 co-localization with LD suggest the activation of lipophagy machinery to counteract the cell engulfment. Lipophagy leads to cholesterol ester (CE) hydrolysis, increasing free cholesterol (FC) secretion, which occurred by specific transporters or unconventional exocytosis pathways, or both. Here, we propose that an unconventional spreading of FC and other lipid metabolites may influence the neurovascular unit (NVU) cells, contributing to Blood brain barrier (BBB) alteration or adaptation, or both, to the cumulative effects of several transient ischemia.
Keywords	oxygen and glucose deprivation ; lipophagy ; lipid droplets ; cholesterol ; ischemia ; vessel disease ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2019-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Repeated intratracheal instillation of PM10 induces lipid reshaping in lung parenchyma and in extra-pulmonary tissues.

Angela Maria Rizzo / Paola Antonia Corsetto / Francesca Farina / Gigliola Montorfano / Giuseppe Pani / Cristina Battaglia / Giulio Sancini / Paola Palestini

PLoS ONE, Vol 9, Iss 9, p e

2014 Volume 106855

Abstract: Adverse health effects of air pollution attributed mainly to airborne particulate matter have been well documented in the last couple of decades. Short term exposure, referring to a few hours exposure, to high ambient PM10 concentration is linked to ... ...

Abstract	Adverse health effects of air pollution attributed mainly to airborne particulate matter have been well documented in the last couple of decades. Short term exposure, referring to a few hours exposure, to high ambient PM10 concentration is linked to increased hospitalization rates for cardiovascular events, typically 24 h after air pollution peaks. Particulate matter exposure is related to pulmonary and cardiovascular diseases, with increased oxidative stress and inflammatory status. Previously, we have demonstrated that repeated intratracheal instillation of PM10sum in BALB/c mice leads to respiratory tract inflammation, creating in lung a condition which could potentially evolve in a systemic toxic reaction. Additionally, plasma membrane and tissue lipids are easily affected by oxidative stress and directly correlated with inflammatory products. With this aim, in the present investigation using the same model, we analyzed the toxic potential of PM10sum exposure on lipid plasma membrane composition, lipid peroxidation and the mechanisms of cells protection in multiple organs such as lung, heart, liver and brain. Obtained results indicated that PM10 exposure led to lung lipid reshaping, in particular phospholipid and cholesterol content increases; concomitantly, the generation of oxidative stress caused lipid peroxidation. In liver we found significant changes in lipid content, mainly due to an increase of phosphatidylcholine, and in total fatty acid composition with a more pronounced level of docosahexaenoic acid; these changes were statistically correlated to lung molecular markers. Heart and brain were similarly affected; heart was significantly enriched in triglycerides in half of the PM10sum treated mice. These results demonstrated a direct involvement of PM10sum in affecting lipid metabolism and oxidative stress in peripheral tissues that might be related to the serious systemic air-pollution effects on human health.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2014-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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