Oxidative stress in cardiovascular disease: myth or fact?

Ceconi, Claudio; Boraso, Antonella; Cargnoni, Anna; Ferrari, Roberto

doi:10.1016/j.abb.2003.06.002

Cited by 146 publications

(108 citation statements)

References 52 publications

Supporting

Mentioning

102

Contrasting

Unclassified

Order By: Relevance

“…Among these alterations, migration and proliferation of vascular smooth muscle cells (VSMCs) are critical for the onset and progression of atherosclerosis, a common problem with increased age [4][5][6]. VSMCs have been shown to shift from a pro-contractile phenotype into a synthetic/proliferative phenotype after an extended period in culture [7,8].…”

Section: Introductionmentioning

confidence: 99%

Impact of Insulin-like Growth Factor-I on Migration, Proliferation and Akt-ERK Signaling in Early and Late-passages of Vascular Smooth Muscle Cells

et al. 2007

View full text Add to dashboard Cite

Migration and proliferation of vascular smooth muscle cells (VSMCs) are important events in the progression of atherosclerosis. Insulin-like growth factor I (IGF-1) possesses both antiapoptotic and mitogenic/motogenic effects in VSMCs although the influence of life cycle on IGF-1-induced effects is unclear. This study was designed to evaluate the effect of IGF-1 on migration, proliferation, and signaling mechanisms in VSMCs from early (3-5) to late (20-22) passages. Migration, proliferation, and cell survival were measured using monolayer wounding, 3 [H]-thymidine incorporation and MTT assay, respectively. Akt and ERK, which are critical to proliferation, differentiation and migration, were examined using Western blot analysis. DCF-DA fluorescence was used to quantify Reactive Oxygen Species (ROS) production. Latepassage VSMCs exhibited significantly higher basal cell proliferation and enhanced sensitivity to IGF-1-stimulated migration compared to cells from early-passages. Phosphorylated Akt and ERK levels were significantly higher in late-passage cells compared to early-passage, which was further enhanced by IGF-1 treatment. Late-passage cells exhibited higher levels of ROS production compared to early-passage, cells. IGF-1 did not significantly alter ROS levels in either passage. Expression of the cell cycle regulator p53, p21, and p16 was not affected by repeated passaging of cells. These results indicated that repeated passaging of VSMCs exhibits a phenotype which has higher proliferative capacity. Activation of trophic signaling molecules such as ERK1/2 and Akt and generation of ROS may represent the mechanisms by which repeated passages of VSMCs acquire a motogenic and mitogenic phenotype.

show abstract

Section: Introductionmentioning

confidence: 99%

Impact of Insulin-like Growth Factor-I on Migration, Proliferation and Akt-ERK Signaling in Early and Late-passages of Vascular Smooth Muscle Cells

et al. 2007

View full text Add to dashboard Cite

show abstract

“…T he association between oxidative stress and characteristic features of the metabolic syndrome, such as diabetes, hypertension, and dyslipidemia, is well documented (1)(2)(3)(4)(5)(6). Human (7) and animal studies (8,9) suggest that the origin of the metabolic syndrome can be traced back to perinatal life, a time when newborn infants are at greater risk of oxidative stress caused by weak antioxidant defenses (10 -12) or exposure to an oxidative environment or both (13)(14)(15)(16)(17)(18).…”

mentioning

confidence: 99%

Neonatal Exposure to Oxidants Induces Later in Life a Metabolic Response Associated to a Phenotype of Energy Deficiency in an Animal Model of Total Parenteral Nutrition

et al. 2010

View full text Add to dashboard Cite

Failure to protect total parenteral nutrition (TPN) from ambient light exacerbates the generation of peroxides, which affects blood glucose and plasma triacylglyceride (TG) in neonates. Based on the concept that the origin of adult diseases can be traced back to perinatal life, it was hypothesized that neonatal exposure to peroxides may affect energy availability later in life. Three-day-old guinea pigs, fitted with a jugular catheter, were fed regular chow (sham) Ϯ i. T he association between oxidative stress and characteristic features of the metabolic syndrome, such as diabetes, hypertension, and dyslipidemia, is well documented (1-6). Human (7) and animal studies (8,9) suggest that the origin of the metabolic syndrome can be traced back to perinatal life, a time when newborn infants are at greater risk of oxidative stress caused by weak antioxidant defenses (10 -12) or exposure to an oxidative environment or both (13-18). Several reports suggest that, in neonates, oxidative stress triggers the events that lead to programming of adult diseases (19 -22).Total parenteral nutrition (TPN) represents a source of oxidants in the form of peroxides that can be calibrated either by applying or not photoprotecting. The peroxides are derived from interactions between dissolved oxygen and electron donors such as lipid, amino acid, or ascorbic acid (23,24). The reaction is catalyzed by photoexcited riboflavin (24). Therefore, the main active agents participating in the generation of peroxides in TPN are ambient light [(ϩ)L] and multivitamin preparations (MVP) (23,24). Photoprotection [(Ϫ)L] of TPN reduces the levels of peroxides by close to 50% (23,25,26). Absence of photoprotection of TPN is associated in preterm newborn infants with higher urinary peroxide concentrations (16), higher blood pressure in girl babies (15), and greater blood glucose and plasma triacylglycerol concentrations (13). Hence, peroxides contaminating TPN solutions are not completely quenched by newborns infants and are thought to be an agent initiating metabolic perturbations. We questioned whether these peroxides are linked to metabolic consequences later in life.Based on the concept that neonatal oxidative stress may interfere with metabolic programming (27), we hypothesized that neonatal exposure to peroxides such as those generated in solutions of parenteral nutrition, induces a permanent modification in lipid and glucose metabolism especially lipogenesis and/or glycolysis. Perturbations in lipid and glucose metabolism, which are fuels for energy production, could have longterm consequences on growth and physical activity, thereby affecting global development. The aim of this study was to measure in adult guinea pigs metabolic responses and spontaneous physical activity after a brief neonatal exposure to i.v. oxidant molecules limited to the first wk of life. A second objective was to assess if these modifications were related to the infusion of peroxides. MATERIALS AND METHODSExperimental design. The metabolic response and the levels...

show abstract

“…Exposure of cells to reactive molecules, including reactive oxygen species and other chemically reactive compounds, can damage cellular macromolecules and compromise cellular functions (1,2,16,20,47). The coordinated induction of phase 2 genes provides an efficient mechanism for mammalian cells to neutralize reactive molecules, eliminate damaged macromolecules, and restore cellular redox homeostasis (8,22,26,33).…”

mentioning

confidence: 99%

CAND1-Mediated Substrate Adaptor Recycling Is Required for Efficient Repression of Nrf2 by Keap1

Hannink

2006

Molecular and Cellular Biology

View full text Add to dashboard Cite

The bZIP transcription factor Nrf2 controls a genetic program that protects cells from oxidative damage and maintains cellular redox homeostasis. Keap1, a BTB-Kelch protein, is the major upstream regulator of Nrf2. Keap1 functions as a substrate adaptor protein for a Cul3-dependent E3 ubiquitin ligase complex to repress steady-state levels of Nrf2 and Nrf2-dependent transcription. Cullin-dependent ubiquitin ligase complexes have been proposed to undergo dynamic cycles of assembly and disassembly that enable substrate adaptor exchange or recycling. In this report, we have characterized the importance of substrate adaptor recycling for regulation of Keap1-mediated repression of Nrf2. Association of Keap1 with Cul3 was decreased by ectopic expression of CAND1 and was increased by small interfering RNA (siRNA)-mediated knockdown of CAND1. However, both ectopic overexpression and siRNA-mediated knockdown of CAND1 decreased the ability of Keap1 to target Nrf2 for ubiquitin-dependent degradation, resulting in stabilization of Nrf2 and activation of Nrf2-dependent gene expression. Neddylation of Cul3 on Lys 712 is required for Keap1-dependent ubiquitination of Nrf2 in vivo. However, the K712R mutant Cul3 molecule, which is not neddylated, can still assemble with Keap1 into a functional ubiquitin ligase complex in vitro. These results provide support for a model in which substrate adaptor recycling is required for efficient substrate ubiquitination by cullin-dependent E3 ubiquitin ligase complexes.

show abstract

Oxidative stress in cardiovascular disease: myth or fact?

Cited by 146 publications

References 52 publications

Impact of Insulin-like Growth Factor-I on Migration, Proliferation and Akt-ERK Signaling in Early and Late-passages of Vascular Smooth Muscle Cells

Impact of Insulin-like Growth Factor-I on Migration, Proliferation and Akt-ERK Signaling in Early and Late-passages of Vascular Smooth Muscle Cells

Neonatal Exposure to Oxidants Induces Later in Life a Metabolic Response Associated to a Phenotype of Energy Deficiency in an Animal Model of Total Parenteral Nutrition

CAND1-Mediated Substrate Adaptor Recycling Is Required for Efficient Repression of Nrf2 by Keap1

Contact Info

Product

Resources

About