Healthy aging: regulation of the metabolome by cellular redox modulation and prooxidant signaling systems: the essential roles of superoxide anion and hydrogen peroxide

Linnane, Anthony W.; Kios, Michael; Vitetta, Luis

doi:10.1007/s10522-007-9096-4

Cited by 103 publications

(96 citation statements)

References 81 publications

(85 reference statements)

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“…Although Zn (II) itself is reported to be an inducer of oxidative stress by promoting mitochondrial and extra-mitochondrial production of ROS 15 , the generation of ROS at a nontoxic level upon Zn (II) exposure/release has not been described. Nevertheless, O2 •− -producing NAD(P)H oxidases are activated in response to growth factors and oncogenes, and enhanced cell proliferation was observed upon ROS-inducing, low-dose photodynamic treatment [38][39][40][41][42] . Therefore, simultaneous increases in cell proliferation and ROS levels are not conflicting.…”

Section: Discussionmentioning

confidence: 99%

Effects of non-toxic zinc exposure on human epidermal keratinocytes

et al. 2015

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Zinc is an essential microelement; its importance to skin is shown by severe skin symptoms in hereditary or acquired zinc deficiency, by the improvement of several skin conditions using systemic or topical zinc preparations and by the induced intracellular zinc release upon UVB exposure, which is the main harmful environmental factor to skin. Understanding the molecular background of the role of zinc in skin may help to gain insight into the pathology of skin disorders and to provide evidence for the therapeutic usefulness of zinc supplementation.Herein, we studied the effect of zinc chloride (ZnCl 2 ) exposure on the function of HaCaT keratinocytes, and we found that a non-toxic elevation in the concentration of extracellular zinc (100 µM) facilitated cell proliferation and induced significant alterations in the mRNA expression of NOTCH1, IL8, and cyclooxygenase-2. In addition, we detected increased heme oxygenase-1 (HMOX1) expression and non-toxic generation of superoxide in the first 4 h.Regarding the effect on UVB-induced toxicity, although the level of cyclobutane pyrimidine dimers in keratinocytes pre-treated with zinc for 24 h was reduced 3 h after UVB irradiation, we found significantly enhanced superoxide generation 10 h after UVB exposure in the zinc pre-exposed cells. The overall survival was unaffected; however, there was a decrease in the percentage of early apoptotic cells and an increase in the percentage of late apoptotic plus necrotic cells.Our results suggest that exposure of human keratinocytes to non-toxic concentrations of ZnCl 2 impacts gene expression, cell proliferation and the response to environmental stress in skin. It would be important to further examine the role of zinc in skin and to further clarify if this issue can affect our thinking about the pathogenesis of skin diseases.

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Section: Discussionmentioning

confidence: 99%

Effects of non-toxic zinc exposure on human epidermal keratinocytes

et al. 2015

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“…ROS are also considered second messengers involved in activation of NF-kappa Beta via tumor necrosis factors (TNF) and interleukin-1 (Baud and Karin 2001), and in regulation of mitogen-activated protein kinase (MAPK) pathways (Sun and Oberley 1996). Through these actions, ROS affect cell function, growth and development and are therefore considered "absolutely essential for the regulation of the metabolome" (Linnane et al 2007). Contrary to conventional wisdom, ROS are not produced in an unregulated manner, requiring immediate neutralization.…”

Section: Oxidative Stress Theory Of Agingmentioning

confidence: 99%

“…In the case of the longest-living rodent, NMR, catalase (CAT) activity is similar to mice, Cu/Zn superoxide dismutase (Cu/ZnSOD) is slightly higher, whereas glutathione peroxidase is 70-fold lower (Andziak et al 2005). An often-touted explanation for the negative correlation between antioxidant activities and species longevity is that enhanced antioxidant defenses are not the reason for extended longevity of long-living mammals, but rather that lower antioxidant levels in longer-living species may be indicative of lower levels of oxidative stress (Barja 2002b(Barja , 2007Ferreira-Cravo et al 2007;Pamplona and Barja 2007;Sanz et al 2006 related increases in ROS production by malfunctioning mitochondria (Linnane et al 2007;Sanz et al 2006). One of the big problems in measuring antioxidant activities is the assumption that "more is better," and that higher levels of antioxidants will equate with reduced oxidative stress (Rando and Epstein 1999).…”

Section: Do Long-living Animals Produce Less Ros Than Shorter-living mentioning

confidence: 99%

“…One of the big problems in measuring antioxidant activities is the assumption that "more is better," and that higher levels of antioxidants will equate with reduced oxidative stress (Rando and Epstein 1999). Despite many years of study of the potential of pharmacological supplementation of traditional antioxidants as an "anti-aging" therapy, there is no well-authenticated study that unequivocally demonstrates a benefit of antioxidant supplementation in mammals (de Grey 2000; Linnane et al 2007;Sanz et al 2006). Indeed, dietary supplementation of antioxidants appears to extend lifespan only when survival of control groups was suboptimal.…”

Section: Do Long-living Animals Produce Less Ros Than Shorter-living mentioning

confidence: 99%

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The oxidative stress theory of aging: embattled or invincible? Insights from non-traditional model organisms

Buffenstein

Edrey

Yang

et al. 2008

AGE

161

131

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Reactive oxygen species (ROS), inevitable byproducts of aerobic metabolism, are known to cause oxidative damage to cells and molecules. This, in turn, is widely accepted as a pivotal determinant of both lifespan and health span. While studies in a wide range of species support the role of ROS in many agerelated diseases, its role in aging per se is questioned. Comparative data from a wide range of endotherms offer equivocal support for this theory, with many exceptions and inconclusive findings as to whether or not oxidative stress is either a correlate or a determinant of maximum species lifespan. Available data do not support the premise that metabolic rate and in vivo ROS production are determinants of lifespan, or that superior antioxidant defense contributes to species longevity. Rather, published studies often show either a negative associate or lack of correlation with species longevity. Furthermore, many long-living species such as birds, bats and mole-rats exhibit high levels of oxidative damage even at young ages. Similarly genetic manipulations altering expression of key antioxidants do not necessarily show an impact on lifespan, even though oxidative damage levels may be affected. While it is possible that these multiple exceptions to straightforward predictions of the free radical theory of aging all reflect speciesspecific, "private" mechanisms of aging, the preponderance of contrary data nevertheless present a challenge to this august theory. Therefore, contrary to accepted dogma, the role of oxidative stress as a determinant of longevity is still open to question.

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“…In fact, in contrast to the destructive effects of reactive oxygen species (ROS), recent evidence indicates that in mammals, hydrogen peroxide (H 2 O 2 ) and other forms of ROS function as essential secondary messengers in the regulation of a variety of physiological processes (reviewed in ref. 5). For example, H 2 O 2 activates prosurvival signaling pathways mediated by p53, NF-κB, AP-1, and other molecules (6).…”

mentioning

confidence: 99%

Caloric restriction or catalase inactivation extends yeast chronological lifespan by inducing H ₂ O ₂ and superoxide dismutase activity

Mesquita

Weinberger²,

Silva³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

248

227

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The free radical theory of aging posits oxidative damage to macromolecules as a primary determinant of lifespan. Recent studies challenge this theory by demonstrating that in some cases, longevity is enhanced by inactivation of oxidative stress defenses or is correlated with increased, rather than decreased reactive oxygen species and oxidative damage. Here we show that, in Saccharomyces cerevisiae, caloric restriction or inactivation of catalases extends chronological lifespan by inducing elevated levels of the reactive oxygen species hydrogen peroxide, which activate superoxide dismutases that inhibit the accumulation of superoxide anions. Increased hydrogen peroxide in catalase-deficient cells extends chronological lifespan despite parallel increases in oxidative damage. These findings establish a role for hormesis effects of hydrogen peroxide in promoting longevity that have broad implications for understanding aging and age-related diseases.aging | hydrogen peroxide | hormesis | antioxidant enzymes | oxidative damage T he longstanding free radical theory has guided investigations into the causes and consequences of aging for more than 50 y (1). However, the results of a number of recent studies have failed to provide support for the free radical theory or suggest that this theory is at best incomplete (2). Studies of naked mole rats, for example, demonstrated that this extremely long-lived rodent exhibits high levels of oxidative damage compared with mice or rats, whose lifespans are ≈1/10 that of naked mole rats (3). In addition, caloric restriction (CR), which extends the lifespans of a variety of eukaryotic organisms, promotes longevity in Caenorhabditis elegans by a mechanism that involves increased oxidative stress (4). In fact, in contrast to the destructive effects of reactive oxygen species (ROS), recent evidence indicates that in mammals, hydrogen peroxide (H 2 O 2 ) and other forms of ROS function as essential secondary messengers in the regulation of a variety of physiological processes (reviewed in ref. 5). For example, H 2 O 2 activates prosurvival signaling pathways mediated by p53, NF-κB, AP-1, and other molecules (6). Furthermore, increases in the intracellular steady-state production of H 2 O 2 by SOD2 overexpression can block the activation of cellular processes required for programmed cell death (7). However, a causal relationship between CR and effects on oxidative stress has been difficult to establish.To better understand how CR impacts oxidative stress and longevity in the model organism Saccharomyces cerevisiae, in this study we examined intracellular levels of H 2 O 2 and superoxide anions (O 2 − ), which are two forms of ROS implicated in aging in all eukaryotes, under CR and other conditions. Our findings indicate that CR or inactivation of catalases extends chronological lifespan (CLS) by inducing elevated levels of H 2 O 2 , which activate superoxide dismutases that inhibit the accumulation of O 2 − . These findings establish a role for hormesis effects of H 2 O 2 in promoting l...

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Healthy aging: regulation of the metabolome by cellular redox modulation and prooxidant signaling systems: the essential roles of superoxide anion and hydrogen peroxide

Cited by 103 publications

References 81 publications

Effects of non-toxic zinc exposure on human epidermal keratinocytes

Effects of non-toxic zinc exposure on human epidermal keratinocytes

The oxidative stress theory of aging: embattled or invincible? Insights from non-traditional model organisms

Caloric restriction or catalase inactivation extends yeast chronological lifespan by inducing H ₂ O ₂ and superoxide dismutase activity

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Healthy aging: regulation of the metabolome by cellular redox modulation and prooxidant signaling systems: the essential roles of superoxide anion and hydrogen peroxide

Cited by 103 publications

References 81 publications

Effects of non-toxic zinc exposure on human epidermal keratinocytes

Effects of non-toxic zinc exposure on human epidermal keratinocytes

The oxidative stress theory of aging: embattled or invincible? Insights from non-traditional model organisms

Caloric restriction or catalase inactivation extends yeast chronological lifespan by inducing H 2 O 2 and superoxide dismutase activity

Contact Info

Product

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Caloric restriction or catalase inactivation extends yeast chronological lifespan by inducing H ₂ O ₂ and superoxide dismutase activity