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Vittorio Calabrese - One of the best experts on this subject based on the ideXlab platform.

  • major pathogenic mechanisms in vascular dementia roles of Cellular Stress Response and hormesis in neuroprotection
    Journal of Neuroscience Research, 2016
    Co-Authors: Vittorio Calabrese, James Giordano, Anna Signorile, Maria Laura Ontario, Sergio Castorina, Concetta De Pasquale, Gunter P Eckert, Edward J Calabrese
    Abstract:

    Abstract Vascular dementia (VaD), considered the second most common cause of cognitive impairment after Alzheimer disease in the elderly, involves the impairment of memory and cognitive function as a consequence of cerebrovascular disease. Chronic cerebral hypoperfusion is a common pathophysiological condition frequently occurring in VaD. It is generally associated with neurovascular degeneration, in which neuronal damage and blood-brain barrier alterations coexist and evoke beta-amyloid-induced oxidative and nitrosative Stress, mitochondrial dysfunction, and inflammasome- promoted neuroinflammation, which contribute to and exacerbate the course of disease. Vascular cognitive impairment comprises a heterogeneous group of cognitive disorders of various severity and types that share a presumed vascular etiology. The present study reviews major pathogenic factors involved in VaD, highlighting the relevance of cerebroCellular Stress and hormetic Responses to neurovascular insult, and addresses these mechanisms as potentially viable and valuable as foci of novel neuroprotective methods to mitigate or prevent VaD. © 2016 Wiley Periodicals, Inc.

  • oxidative Stress glutathione status sirtuin and Cellular Stress Response in type 2 diabetes
    Biochimica et Biophysica Acta, 2012
    Co-Authors: Vittorio Calabrese, Carolin Cornelius, Veruscka Leso, A Trovatosalinaro, B Ventimiglia, M Cavallaro, Maria Scuto, S Rizza, Luca Zanoli
    Abstract:

    Abstract Oxidative Stress has been suggested to play a main role in the pathogenesis of type 2 diabetes mellitus and its complications. As a consequence of this increased oxidative status a Cellular adaptive Response occurs requiring functional chaperones, antioxidant production and protein degradation. This study was designed to evaluate systemic oxidative Stress and Cellular Stress Response in patients suffering from type 2 diabetes and in age-matched healthy subjects. Systemic oxidative Stress has been evaluated by measuring plasma reduced and oxidized glutathione, as well as pentosidine, protein carbonyls lipid oxidation products 4-hydroxy-2-nonenal and F2-isoprostanes in plasma, and lymphocytes, whereas the lymphocyte levels of the heat shock proteins (HSP) HO-1, Hsp72, Sirtuin-1, Sirtuin-2 and thioredoxin reductase-1 (TrxR-1) have been measured to evaluate the systemic Cellular Stress Response. Plasma GSH/GSSG showed a significant decrease in type 2 diabetes as compared to control group, associated with increased pentosidine, F2-isoprostanes, carbonyls and HNE levels. In addition, lymphocyte levels of HO-1, Hsp70, Trx and TrxR-1 (P

  • oxidative Stress glutathione status sirtuin and Cellular Stress Response in type 2 diabetes
    Biochimica et Biophysica Acta, 2012
    Co-Authors: Vittorio Calabrese, Carolin Cornelius, Veruscka Leso, A Trovatosalinaro, B Ventimiglia, M Cavallaro, Maria Scuto, S Rizza, Luca Zanoli
    Abstract:

    Oxidative Stress has been suggested to play a main role in the pathogenesis of type 2 diabetes mellitus and its complications. As a consequence of this increased oxidative status a Cellular adaptive Response occurs requiring functional chaperones, antioxidant production and protein degradation. This study was designed to evaluate systemic oxidative Stress and Cellular Stress Response in patients suffering from type 2 diabetes and in age-matched healthy subjects. Systemic oxidative Stress has been evaluated by measuring plasma reduced and oxidized glutathione, as well as pentosidine, protein carbonyls lipid oxidation products 4-hydroxy-2-nonenal and F2-isoprostanes in plasma, and lymphocytes, whereas the lymphocyte levels of the heat shock proteins (HSP) HO-1, Hsp72, Sirtuin-1, Sirtuin-2 and thioredoxin reductase-1 (TrxR-1) have been measured to evaluate the systemic Cellular Stress Response. Plasma GSH/GSSG showed a significant decrease in type 2 diabetes as compared to control group, associated with increased pentosidine, F2-isoprostanes, carbonyls and HNE levels. In addition, lymphocyte levels of HO-1, Hsp70, Trx and TrxR-1 (P<0.05 and P<0.01) in diabetic patients were higher than in normal subjects, while sirtuin-1 and sirtuin-2 protein was significantly decreased (p<0.05). In conclusion, patients affected by type 2 diabetes are under condition of systemic oxidative Stress and, although the relevance of downregulation in sirtuin signal has to be fully understood, however induction of HSPs and thioredoxin protein system represent a maintained Response in counteracting systemic pro-oxidant status. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease.

  • hormesis Cellular Stress Response and vitagenes as critical determinants in aging and longevity
    Molecular Aspects of Medicine, 2011
    Co-Authors: Vittorio Calabrese, Carolin Cornelius, Enrico Rizzarelli, Salvatore Cuzzocrea, Ivo Iavicoli, Edward J Calabrese
    Abstract:

    Abstract Understanding mechanisms of aging and determinants of life span will help to reduce age-related morbidity and facilitate healthy aging. Average lifespan has increased over the last centuries, as a consequence of medical and environmental factors, but maximal life span remains unchanged. Extension of maximal life span is currently possible in animal models with measures such as genetic manipulations and caloric restriction (CR). CR appears to prolong life by reducing reactive oxygen species (ROS)-mediated oxidative damage. But ROS formation, which is positively implicated in Cellular Stress Response mechanisms, is a highly regulated process controlled by a complex network of intraCellular signaling pathways. By sensing the intraCellular nutrient and energy status, the functional state of mitochondria, and the concentration of ROS produced in mitochondria, the longevity network regulates life span across species by co-ordinating information flow along its convergent, divergent and multiply branched signaling pathways, including vitagenes which are genes involved in preserving Cellular homeostasis during Stressful conditions. Vitagenes encode for heat shock proteins (Hsp) Hsp32, Hsp70, the thioredoxin and the sirtuin protein systems. Dietary antioxidants, such as carnosine, carnitines or polyphenols, have recently been demonstrated to be neuroprotective through the activation of hormetic pathways, including vitagenes. The hormetic dose–Response, challenges long-standing beliefs about the nature of the dose–Response in a lowdose zone, having the potential to affect significantly the design of pre-clinical studies and clinical trials as well as strategies for optimal patient dosing in the treatment of numerous diseases. Given the broad cytoprotective properties of the heat shock Response there is now strong interest in discovering and developing pharmacological agents capable of inducing Stress Responses. In this review we discuss the most current and up to date understanding of the possible signaling mechanisms by which caloric restriction, as well hormetic caloric restriction–mimetics compounds by activating vitagenes can enhance defensive systems involved in bioenergetic and Stress resistance homeostasis with consequent impact on longevity processes.

  • redox homeostasis and Cellular Stress Response in aging and neurodegeneration
    Methods of Molecular Biology, 2010
    Co-Authors: Vittorio Calabrese, Carolin Cornelius, Cesare Mancuso, Riccardo Lentile, A Giuffrida M Stella, Allan D Butterfield
    Abstract:

    Decreased expression and/or activity of antioxidant proteins leads to oxidative Stress, accelerated aging, and neurodegeneration. While overwhelming levels and uncontrolled/dysregulated actions of reactive oxygen species (ROS) lead to deleterious effects, tighter regulation of those plays an important role in cell signaling. Mutations causing protein misfolding and the overload of toxic products derived from the free radical oxidation of polyunsaturated fatty acids, cholesterol, and glucose contribute to the disruption of the Cellular redox homeostasis. Collectively or individually, these effects create pro-oxidant conditions in cells. Oxidative Stress can induce neuronal damage, modulate intraCellular signaling, and can ultimately lead to neuronal death by apoptosis or necrosis. Emerging evidence indicates that homocysteine (Hcy), a non-protein amino acid naturally present in the plasma, is implicated as a risk factor for numerous diseases. In particular, increased levels of circulating Hcy have been recognized as an independent risk factor for the development of vascular disease(s). Recent findings emphasize a relationship between elevated Hcy levels and neurodegeneration, which can be observed in Alzheimer's and Parkinson's diseases. An integrated Response exists in the brain to detect and control diverse forms of Stress. This is accomplished by a complex network of the so-called longevity assurance processes, which are controlled by several genes termed "vitagenes." Among these, the heat-shock proteins (HSPs) form a highly conserved system that is responsible for the preservation and repair of the correct protein conformation. Recent studies have shown that the heat-shock Response (HSR) contributes to cytoprotection in a number of human diseases including inflammation, cancer, aging, and neurodegenerative disorders. Given the broad cytoprotective properties of the HSR, interest mounts currently among investigators toward discovering and developing pharmacological agents capable of inducing HSR. L: -Acetylcarnitine (LAC) is proposed as a therapeutic agent for several neurodegenerative disorders and also current evidence suggests that the compound may play a critical role in the modulation of Cellular Stress Response in health and disease conditions. Here, we review the emerging salient concepts highlighting the pathways of neurodegeneration and the role of LAC in modulating the redox-dependent mechanisms responsible for the upregulation of vitagenes in brain that leads to the enhancement of Stress tolerance in brain.

Carolin Cornelius - One of the best experts on this subject based on the ideXlab platform.

  • osteoporosis and alzheimer pathology role of Cellular Stress Response and hormetic redox signaling in aging and bone remodeling
    Frontiers in Pharmacology, 2014
    Co-Authors: Carolin Cornelius, Maria Scuto, Salvatore Cuzzocrea, Guido Koverech, Rosalia Crupi, Rosanna Di Paola, Angela Koverech, Francesca Lodato, Angela Trovato Salinaro, Edward J Calabrese
    Abstract:

    Alzheimer’s disease (AD) as well as osteoporosis are multifactorial progressive degenerative disorders characterized by low parenchymal density and microarchitectural deterioration of tissue. Though not referred to as one of the major complications of AD, osteoporosis and hip fracture are commonly observed in patients with AD, however, the mechanisms underlying this association remain poorly understood. Reactive oxygen species (ROS) are generally recognized as intraCellular redox signaling molecules involved in the regulation of bone metabolism, including receptor activator of nuclear factor-kB ligand (RANKL)-dependent osteoclast differentiation, but they also have cytotoxic effects that include peroxidation of lipids and oxidative damage to proteins and DNA. ROS formation, which is positively implicated in Cellular Stress Response mechanisms, is a highly regulated process controlled by a complex network of intraCellular signaling pathways which regulate life span across species including vitagenes which are genes involved in preserving Cellular homeostasis during Stressful conditions. Vitagenes encode for heat shock proteins (Hsp) Hsp32, Hsp70, the thioredoxin and the sirtuin protein systems. Dietary antioxidants, have recently been demonstrated to be neuroprotective through the activation of hormetic pathways, including vitagenes. The hormetic dose–Response, has the potential to affect significantly the design of pre-clinical studies and clinical trials as well as strategies for optimal patient dosing in the treatment of numerous diseases. Given the broad cytoprotective properties of the heat shock Response there is now strong interest in discovering and developing pharmacological agents capable of inducing Stress Responses. Here we focus on possible signaling mechanisms involved in bone remodeling and activation of vitagenes resulting in enhanced defense against energy and Stress resistance homeostasis dysruption with consequent impact on aging processes.

  • oxidative Stress glutathione status sirtuin and Cellular Stress Response in type 2 diabetes
    Biochimica et Biophysica Acta, 2012
    Co-Authors: Vittorio Calabrese, Carolin Cornelius, Veruscka Leso, A Trovatosalinaro, B Ventimiglia, M Cavallaro, Maria Scuto, S Rizza, Luca Zanoli
    Abstract:

    Abstract Oxidative Stress has been suggested to play a main role in the pathogenesis of type 2 diabetes mellitus and its complications. As a consequence of this increased oxidative status a Cellular adaptive Response occurs requiring functional chaperones, antioxidant production and protein degradation. This study was designed to evaluate systemic oxidative Stress and Cellular Stress Response in patients suffering from type 2 diabetes and in age-matched healthy subjects. Systemic oxidative Stress has been evaluated by measuring plasma reduced and oxidized glutathione, as well as pentosidine, protein carbonyls lipid oxidation products 4-hydroxy-2-nonenal and F2-isoprostanes in plasma, and lymphocytes, whereas the lymphocyte levels of the heat shock proteins (HSP) HO-1, Hsp72, Sirtuin-1, Sirtuin-2 and thioredoxin reductase-1 (TrxR-1) have been measured to evaluate the systemic Cellular Stress Response. Plasma GSH/GSSG showed a significant decrease in type 2 diabetes as compared to control group, associated with increased pentosidine, F2-isoprostanes, carbonyls and HNE levels. In addition, lymphocyte levels of HO-1, Hsp70, Trx and TrxR-1 (P

  • oxidative Stress glutathione status sirtuin and Cellular Stress Response in type 2 diabetes
    Biochimica et Biophysica Acta, 2012
    Co-Authors: Vittorio Calabrese, Carolin Cornelius, Veruscka Leso, A Trovatosalinaro, B Ventimiglia, M Cavallaro, Maria Scuto, S Rizza, Luca Zanoli
    Abstract:

    Oxidative Stress has been suggested to play a main role in the pathogenesis of type 2 diabetes mellitus and its complications. As a consequence of this increased oxidative status a Cellular adaptive Response occurs requiring functional chaperones, antioxidant production and protein degradation. This study was designed to evaluate systemic oxidative Stress and Cellular Stress Response in patients suffering from type 2 diabetes and in age-matched healthy subjects. Systemic oxidative Stress has been evaluated by measuring plasma reduced and oxidized glutathione, as well as pentosidine, protein carbonyls lipid oxidation products 4-hydroxy-2-nonenal and F2-isoprostanes in plasma, and lymphocytes, whereas the lymphocyte levels of the heat shock proteins (HSP) HO-1, Hsp72, Sirtuin-1, Sirtuin-2 and thioredoxin reductase-1 (TrxR-1) have been measured to evaluate the systemic Cellular Stress Response. Plasma GSH/GSSG showed a significant decrease in type 2 diabetes as compared to control group, associated with increased pentosidine, F2-isoprostanes, carbonyls and HNE levels. In addition, lymphocyte levels of HO-1, Hsp70, Trx and TrxR-1 (P<0.05 and P<0.01) in diabetic patients were higher than in normal subjects, while sirtuin-1 and sirtuin-2 protein was significantly decreased (p<0.05). In conclusion, patients affected by type 2 diabetes are under condition of systemic oxidative Stress and, although the relevance of downregulation in sirtuin signal has to be fully understood, however induction of HSPs and thioredoxin protein system represent a maintained Response in counteracting systemic pro-oxidant status. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease.

  • hormesis Cellular Stress Response and vitagenes as critical determinants in aging and longevity
    Molecular Aspects of Medicine, 2011
    Co-Authors: Vittorio Calabrese, Carolin Cornelius, Enrico Rizzarelli, Salvatore Cuzzocrea, Ivo Iavicoli, Edward J Calabrese
    Abstract:

    Abstract Understanding mechanisms of aging and determinants of life span will help to reduce age-related morbidity and facilitate healthy aging. Average lifespan has increased over the last centuries, as a consequence of medical and environmental factors, but maximal life span remains unchanged. Extension of maximal life span is currently possible in animal models with measures such as genetic manipulations and caloric restriction (CR). CR appears to prolong life by reducing reactive oxygen species (ROS)-mediated oxidative damage. But ROS formation, which is positively implicated in Cellular Stress Response mechanisms, is a highly regulated process controlled by a complex network of intraCellular signaling pathways. By sensing the intraCellular nutrient and energy status, the functional state of mitochondria, and the concentration of ROS produced in mitochondria, the longevity network regulates life span across species by co-ordinating information flow along its convergent, divergent and multiply branched signaling pathways, including vitagenes which are genes involved in preserving Cellular homeostasis during Stressful conditions. Vitagenes encode for heat shock proteins (Hsp) Hsp32, Hsp70, the thioredoxin and the sirtuin protein systems. Dietary antioxidants, such as carnosine, carnitines or polyphenols, have recently been demonstrated to be neuroprotective through the activation of hormetic pathways, including vitagenes. The hormetic dose–Response, challenges long-standing beliefs about the nature of the dose–Response in a lowdose zone, having the potential to affect significantly the design of pre-clinical studies and clinical trials as well as strategies for optimal patient dosing in the treatment of numerous diseases. Given the broad cytoprotective properties of the heat shock Response there is now strong interest in discovering and developing pharmacological agents capable of inducing Stress Responses. In this review we discuss the most current and up to date understanding of the possible signaling mechanisms by which caloric restriction, as well hormetic caloric restriction–mimetics compounds by activating vitagenes can enhance defensive systems involved in bioenergetic and Stress resistance homeostasis with consequent impact on longevity processes.

  • redox homeostasis and Cellular Stress Response in aging and neurodegeneration
    Methods of Molecular Biology, 2010
    Co-Authors: Vittorio Calabrese, Carolin Cornelius, Cesare Mancuso, Riccardo Lentile, A Giuffrida M Stella, Allan D Butterfield
    Abstract:

    Decreased expression and/or activity of antioxidant proteins leads to oxidative Stress, accelerated aging, and neurodegeneration. While overwhelming levels and uncontrolled/dysregulated actions of reactive oxygen species (ROS) lead to deleterious effects, tighter regulation of those plays an important role in cell signaling. Mutations causing protein misfolding and the overload of toxic products derived from the free radical oxidation of polyunsaturated fatty acids, cholesterol, and glucose contribute to the disruption of the Cellular redox homeostasis. Collectively or individually, these effects create pro-oxidant conditions in cells. Oxidative Stress can induce neuronal damage, modulate intraCellular signaling, and can ultimately lead to neuronal death by apoptosis or necrosis. Emerging evidence indicates that homocysteine (Hcy), a non-protein amino acid naturally present in the plasma, is implicated as a risk factor for numerous diseases. In particular, increased levels of circulating Hcy have been recognized as an independent risk factor for the development of vascular disease(s). Recent findings emphasize a relationship between elevated Hcy levels and neurodegeneration, which can be observed in Alzheimer's and Parkinson's diseases. An integrated Response exists in the brain to detect and control diverse forms of Stress. This is accomplished by a complex network of the so-called longevity assurance processes, which are controlled by several genes termed "vitagenes." Among these, the heat-shock proteins (HSPs) form a highly conserved system that is responsible for the preservation and repair of the correct protein conformation. Recent studies have shown that the heat-shock Response (HSR) contributes to cytoprotection in a number of human diseases including inflammation, cancer, aging, and neurodegenerative disorders. Given the broad cytoprotective properties of the HSR, interest mounts currently among investigators toward discovering and developing pharmacological agents capable of inducing HSR. L: -Acetylcarnitine (LAC) is proposed as a therapeutic agent for several neurodegenerative disorders and also current evidence suggests that the compound may play a critical role in the modulation of Cellular Stress Response in health and disease conditions. Here, we review the emerging salient concepts highlighting the pathways of neurodegeneration and the role of LAC in modulating the redox-dependent mechanisms responsible for the upregulation of vitagenes in brain that leads to the enhancement of Stress tolerance in brain.

Luca Zanoli - One of the best experts on this subject based on the ideXlab platform.

  • oxidative Stress glutathione status sirtuin and Cellular Stress Response in type 2 diabetes
    Biochimica et Biophysica Acta, 2012
    Co-Authors: Vittorio Calabrese, Carolin Cornelius, Veruscka Leso, A Trovatosalinaro, B Ventimiglia, M Cavallaro, Maria Scuto, S Rizza, Luca Zanoli
    Abstract:

    Abstract Oxidative Stress has been suggested to play a main role in the pathogenesis of type 2 diabetes mellitus and its complications. As a consequence of this increased oxidative status a Cellular adaptive Response occurs requiring functional chaperones, antioxidant production and protein degradation. This study was designed to evaluate systemic oxidative Stress and Cellular Stress Response in patients suffering from type 2 diabetes and in age-matched healthy subjects. Systemic oxidative Stress has been evaluated by measuring plasma reduced and oxidized glutathione, as well as pentosidine, protein carbonyls lipid oxidation products 4-hydroxy-2-nonenal and F2-isoprostanes in plasma, and lymphocytes, whereas the lymphocyte levels of the heat shock proteins (HSP) HO-1, Hsp72, Sirtuin-1, Sirtuin-2 and thioredoxin reductase-1 (TrxR-1) have been measured to evaluate the systemic Cellular Stress Response. Plasma GSH/GSSG showed a significant decrease in type 2 diabetes as compared to control group, associated with increased pentosidine, F2-isoprostanes, carbonyls and HNE levels. In addition, lymphocyte levels of HO-1, Hsp70, Trx and TrxR-1 (P

  • oxidative Stress glutathione status sirtuin and Cellular Stress Response in type 2 diabetes
    Biochimica et Biophysica Acta, 2012
    Co-Authors: Vittorio Calabrese, Carolin Cornelius, Veruscka Leso, A Trovatosalinaro, B Ventimiglia, M Cavallaro, Maria Scuto, S Rizza, Luca Zanoli
    Abstract:

    Oxidative Stress has been suggested to play a main role in the pathogenesis of type 2 diabetes mellitus and its complications. As a consequence of this increased oxidative status a Cellular adaptive Response occurs requiring functional chaperones, antioxidant production and protein degradation. This study was designed to evaluate systemic oxidative Stress and Cellular Stress Response in patients suffering from type 2 diabetes and in age-matched healthy subjects. Systemic oxidative Stress has been evaluated by measuring plasma reduced and oxidized glutathione, as well as pentosidine, protein carbonyls lipid oxidation products 4-hydroxy-2-nonenal and F2-isoprostanes in plasma, and lymphocytes, whereas the lymphocyte levels of the heat shock proteins (HSP) HO-1, Hsp72, Sirtuin-1, Sirtuin-2 and thioredoxin reductase-1 (TrxR-1) have been measured to evaluate the systemic Cellular Stress Response. Plasma GSH/GSSG showed a significant decrease in type 2 diabetes as compared to control group, associated with increased pentosidine, F2-isoprostanes, carbonyls and HNE levels. In addition, lymphocyte levels of HO-1, Hsp70, Trx and TrxR-1 (P<0.05 and P<0.01) in diabetic patients were higher than in normal subjects, while sirtuin-1 and sirtuin-2 protein was significantly decreased (p<0.05). In conclusion, patients affected by type 2 diabetes are under condition of systemic oxidative Stress and, although the relevance of downregulation in sirtuin signal has to be fully understood, however induction of HSPs and thioredoxin protein system represent a maintained Response in counteracting systemic pro-oxidant status. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease.

Heiner Schafer - One of the best experts on this subject based on the ideXlab platform.

  • role of the immediate early Response 3 ier3 gene in Cellular Stress Response inflammation and tumorigenesis
    European Journal of Cell Biology, 2011
    Co-Authors: Alexander Arlt, Heiner Schafer
    Abstract:

    The expression of the early Response gene immediate early Response 3 (IER3), formerly known as IEX-1, is induced by a great variety of stimuli, such as growth factors, cytokines, ionizing radiation, viral infection and other types of Cellular Stress. Being of a rather unique protein structure not sharing any similarity to other vertebrate proteins, IER3 plays a complex and to some extent contradictory role in cell cycle control and apoptosis. As outlined in this review, these effects of IER3 relate to an interference with certain signalling pathways, in particular NF-κB, MAPK/ERK and PI3K/Akt. In addition to numerous functional data relying on cell culture based studies, transgenic and knock-out mouse models revealed an involvement of IER3 expression in immune functions and in the physiology of the cardiovascular system. Deficiency of IER3 expression in mice results in an aberrant immune regulation and enhanced inflammation, in an alteration of blood pressure control and hypertension or in an impaired genomic stability. A number of patient related studies revealed an involvement of IER3 in tumorigenesis in a cell-type dependent but not yet understood manner. Future studies should establish the potential of IER3 as a new predictive marker and as a molecular target in human diseases such as cancer, inflammatory diseases or hypertension.

  • role of the immediate early Response 3 ier3 gene in Cellular Stress Response inflammation and tumorigenesis
    European Journal of Cell Biology, 2011
    Co-Authors: Alexander Arlt, Heiner Schafer
    Abstract:

    The expression of the early Response gene immediate early Response 3 (IER3), formerly known as IEX-1, is induced by a great variety of stimuli, such as growth factors, cytokines, ionizing radiation, viral infection and other types of Cellular Stress. Being of a rather unique protein structure not sharing any similarity to other vertebrate proteins. IER3 plays a complex and to some extent contradictory role in cell cycle control and apoptosis. As outlined in this review, these effects of IER3 relate to an interference with certain signalling pathways, in particular NF-kappa B, MAPK/ERK and PI3K/Akt. In addition to numerous functional data relying on cell culture based studies, transgenic and knock-out mouse models revealed an involvement of IER3 expression in immune functions and in the physiology of the cardiovascular system. Deficiency of IER3 expression in mice results in an aberrant immune regulation and enhanced inflammation, in an alteration of blood pressure control and hypertension or in an impaired genomic stability. A number of patient related studies revealed an involvement of IER3 in tumorigenesis in a cell-type dependent but not yet understood manner. Future studies should establish the potential of IER3 as a new predictive marker and as a molecular target in human diseases such as cancer, inflammatory diseases or hypertension. (C) 2010 Elsevier GmbH. All rights reserved.

Veruscka Leso - One of the best experts on this subject based on the ideXlab platform.

  • oxidative Stress glutathione status sirtuin and Cellular Stress Response in type 2 diabetes
    Biochimica et Biophysica Acta, 2012
    Co-Authors: Vittorio Calabrese, Carolin Cornelius, Veruscka Leso, A Trovatosalinaro, B Ventimiglia, M Cavallaro, Maria Scuto, S Rizza, Luca Zanoli
    Abstract:

    Abstract Oxidative Stress has been suggested to play a main role in the pathogenesis of type 2 diabetes mellitus and its complications. As a consequence of this increased oxidative status a Cellular adaptive Response occurs requiring functional chaperones, antioxidant production and protein degradation. This study was designed to evaluate systemic oxidative Stress and Cellular Stress Response in patients suffering from type 2 diabetes and in age-matched healthy subjects. Systemic oxidative Stress has been evaluated by measuring plasma reduced and oxidized glutathione, as well as pentosidine, protein carbonyls lipid oxidation products 4-hydroxy-2-nonenal and F2-isoprostanes in plasma, and lymphocytes, whereas the lymphocyte levels of the heat shock proteins (HSP) HO-1, Hsp72, Sirtuin-1, Sirtuin-2 and thioredoxin reductase-1 (TrxR-1) have been measured to evaluate the systemic Cellular Stress Response. Plasma GSH/GSSG showed a significant decrease in type 2 diabetes as compared to control group, associated with increased pentosidine, F2-isoprostanes, carbonyls and HNE levels. In addition, lymphocyte levels of HO-1, Hsp70, Trx and TrxR-1 (P

  • oxidative Stress glutathione status sirtuin and Cellular Stress Response in type 2 diabetes
    Biochimica et Biophysica Acta, 2012
    Co-Authors: Vittorio Calabrese, Carolin Cornelius, Veruscka Leso, A Trovatosalinaro, B Ventimiglia, M Cavallaro, Maria Scuto, S Rizza, Luca Zanoli
    Abstract:

    Oxidative Stress has been suggested to play a main role in the pathogenesis of type 2 diabetes mellitus and its complications. As a consequence of this increased oxidative status a Cellular adaptive Response occurs requiring functional chaperones, antioxidant production and protein degradation. This study was designed to evaluate systemic oxidative Stress and Cellular Stress Response in patients suffering from type 2 diabetes and in age-matched healthy subjects. Systemic oxidative Stress has been evaluated by measuring plasma reduced and oxidized glutathione, as well as pentosidine, protein carbonyls lipid oxidation products 4-hydroxy-2-nonenal and F2-isoprostanes in plasma, and lymphocytes, whereas the lymphocyte levels of the heat shock proteins (HSP) HO-1, Hsp72, Sirtuin-1, Sirtuin-2 and thioredoxin reductase-1 (TrxR-1) have been measured to evaluate the systemic Cellular Stress Response. Plasma GSH/GSSG showed a significant decrease in type 2 diabetes as compared to control group, associated with increased pentosidine, F2-isoprostanes, carbonyls and HNE levels. In addition, lymphocyte levels of HO-1, Hsp70, Trx and TrxR-1 (P<0.05 and P<0.01) in diabetic patients were higher than in normal subjects, while sirtuin-1 and sirtuin-2 protein was significantly decreased (p<0.05). In conclusion, patients affected by type 2 diabetes are under condition of systemic oxidative Stress and, although the relevance of downregulation in sirtuin signal has to be fully understood, however induction of HSPs and thioredoxin protein system represent a maintained Response in counteracting systemic pro-oxidant status. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease.