Age-related changes in manganese superoxide dismutase activity in the cerebral cortex of senescence-accelerated prone and resistant mouse

Kurokáwa, Tomonori; Asada, Shinji; Nishitani, Shinobu; Hazeki, Osamu

doi:10.1016/s0304-3940(00)01755-9

Cited by 47 publications

(22 citation statements)

References 18 publications

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“…In the absence of a change in superoxide anion formation, oxidative stress would be expected to arise as a consequence of a compromised antioxidant defence capability. In this context, the significant reductions in reduced glutathione (Nogués et al 2006) and superoxide dismutase (Kurokawa et al 2001) levels observed in the SAMP8 mice relative to the control SAMR1 strain would be expected to generate a state of oxidative stress throughout the body. The mechanisms underpinning these changes are not fully resolved but may involve a self-propagating cycle of oxidative damage, whereby the carbonyl modifications associated with free radical attacks on proteins lead to the inactivation of antioxidant enzymes (Nabeshi et al 2006), creating yet more oxidative stress and leading to a further deterioration of the antioxidant protection system.…”

Section: Discussionmentioning

confidence: 99%

The senescence-accelerated mouse prone 8 as a model for oxidative stress and impaired DNA repair in the male germ line

Smith¹,

Iuliis²,

Lord³

et al. 2013

Reproduction

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The discovery of a truncated base excision repair pathway in human spermatozoa mediated by OGG1 has raised questions regarding the effect of mutations in critical DNA repair genes on the integrity of the paternal genome. The senescence-accelerated mouse prone 8 (SAMP8) is a mouse model containing a suite of naturally occurring mutations resulting in an accelerated senescence phenotype largely mediated by oxidative stress, which is further enhanced by a mutation in the Ogg1 gene, greatly reducing the ability of the enzyme to excise 8-hydroxy,2 0 -deoxyguanosine (8OHdG) adducts. An analysis of the reproductive phenotype of the SAMP8 males revealed a high level of DNA damage in caudal epididymal spermatozoa as measured by the alkaline Comet assay. Furthermore, these lesions were confirmed to be oxidative in nature, as demonstrated by significant increases in 8OHdG adduct formation in the SAMP8 testicular tissue (P!0.05) as well as in mature spermatozoa (P!0.001) relative to a control strain (SAMR1). Despite this high level of oxidative DNA damage in spermatozoa, reactive oxygen species generation was not elevated and motility of spermatozoa was found to be similar to that for the control strain with the exception of progressive motility, which exhibited a slight but significant decline with advancing age (P!0.05). When challenged with Fenton reagents (H 2 O 2 and Fe 2C ), the SAMP8 spermatozoa demonstrated a highly increased susceptibility to formation of 8OHdG adducts compared with the controls (P!0.001). These data highlight the role of oxidative stress and OGG1-dependent base excision repair mechanisms in defining the genetic integrity of mammalian spermatozoa.

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Section: Discussionmentioning

confidence: 99%

The senescence-accelerated mouse prone 8 as a model for oxidative stress and impaired DNA repair in the male germ line

Smith¹,

Iuliis²,

Lord³

et al. 2013

Reproduction

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“…Interestingly, there is significant evidence that SAMP8 mice (age 1-5 months) possess a more elevated oxidative status compared with SAMR1 controls (Liu & Mori, 1993;Sato et al, 1996a,b;Kurokawa et al, 2001;Yasui et al, 2002Yasui et al, , 2003Farr et al, 2003;Poon et al, 2004a;Alvarez-García et al, 2006). In the current study, we demonstrated that SAMP8 astrocyte cultures present increased superoxide radical generation, lipoperoxidation and carbonyl proteins vs. SAMR1, which is consistent with in vivo studies.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, increasing evidence of elevated oxidative stress in the aged SAMP8 brain has been reported. Increased levels of lipoperoxidation, carbonyl proteins and ROS in the brain of SAMP8 mice have been observed, together with learning and memory deficits as early as 1-5 months of age (Liu & Mori, 1993;Sato et al ., 1996a,b;Kurokawa et al ., 2001;Yasui et al ., 2002Yasui et al ., , 2003Farr et al ., 2003;Poon et al ., 2004a;AlvarezGarcía et al ., 2006). In addition, chronic administration of antioxidants, such as melatonin, α -lipoic acid, N-acetylcysteine and acetyl-L-carnitine, to SAMP8 mice not only reduced oxidative damage to neural lipids and proteins, but also lessened cognitive deficits (Okatani et al ., 2002;Yasui et al ., 2002;Farr et al ., 2003;Poon et al ., 2005).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, chronic administration of antioxidants, such as melatonin, α -lipoic acid, N-acetylcysteine and acetyl-L-carnitine, to SAMP8 mice not only reduced oxidative damage to neural lipids and proteins, but also lessened cognitive deficits (Okatani et al ., 2002;Yasui et al ., 2002;Farr et al ., 2003;Poon et al ., 2005). Decreases in superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase activities, as well as increases in acyl-CoA oxidase, which have been detected early in SAMP8 mice (1-12 months) compared with age-matched SAMR1 controls (Sato et al ., 1996b;Kurokawa et al ., 2001;Okatani et al ., 2002;Alvarez-García et al ., 2006;Sureda et al ., 2006), may cause elevated generation of ROS. On the other hand, ROS generated by mitochondria or from other cell sites not only cause damage to mitochondrial components and DNA, but also trigger degradative processes that contribute to the aging process (Cadenas & Davies, 2000;Manczak et al ., 2005).…”

Section: Introductionmentioning

confidence: 99%

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Dysfunction of astrocytes in senescence‐accelerated mice SAMP8 reduces their neuroprotective capacity

et al. 2008

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SummaryEarly onset increases in oxidative stress and tau pathology are present in the brain of senescence-accelerated mice prone (SAMP8). Astrocytes play an essential role, both in determining the brain's susceptibility to oxidative damage and in protecting neurons. In this study, we examine changes in tau phosphorylation, oxidative stress and glutamate uptake in primary cultures of cortical astrocytes from neonatal SAMP8 mice and senescenceaccelerated-resistant mice (SAMR1). We demonstrated an enhancement of abnormally phosphorylated tau in Ser 199 and Ser 396 in SAMP8 astrocytes compared with that of SAMR1 control mice. Gsk3β β β β and Cdk5 kinase activity, which regulate tau phosphorylation, was also increased in SAMP8 astrocytes. Inhibition of Gsk3β β β β by lithium or Cdk5 by roscovitine reduced tau phosphorylation at Ser 396 .Moreover, we detected an increase in radical superoxide generation, which may be responsible for the corresponding increase in lipoperoxidation and protein oxidation. We also observed a reduced mitochondrial membrane potential in SAMP8 mouse astrocytes. Glutamate uptake in astrocytes is a critical neuroprotective mechanism. SAMP8 astrocytes showed a decreased glutamate uptake compared with those of SAMR1 controls. Interestingly, survival of SAMP8 or SAMR1 neurons cocultured with SAMP8 astrocytes was significantly reduced. Our results indicate that alterations in astrocyte cultures from SAMP8 mice are similar to those detected in whole brains of SAMP8 mice at 1-5 months. Moreover, our findings suggest that this in vitro preparation is suitable for studying the molecular and cellular processes underlying early aging in this murine model. In addition, our study supports the contention that astrocytes play a key role in neurodegeneration during the aging process.

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“…In this study, there was reported to be elevated activity of monoamine oxidase B (MAO-B) and decreased activity of superoxide dismutase (SOD) in SAM-P mice versus SAM-R mice (Nomura et al, 1989). After that, more detailed studies were performed specifically in the SAMP8 strain where there was reported to be a decrease in manganese superoxide dismutase (Mn-SOD) activity in 10-month-old SAMP8 mice (Kurokawa et al, 2001), and an age-related decrease in Cu/Zn superoxide dismutase (Cu/Zn-SOD) expression in 5 to 15-month-old SAMP8 mice (Zhu et al, 2011), as well as in activity of glutathione peroxidase in 12-month-old SAMP8 mice (Okatani et al, 2002). Furthermore, glutathione reductase, glutathione peroxidase and catalase activities were lower in 5-month-old SAMP8 mice than in aged-matched SAMR1 mice (Sureda et al, 2006).…”

Section: Oxidative Stressmentioning

confidence: 99%

Modulation of Signal Transduction Pathways in Senescence-Accelerated Mice P8 Strain: A Useful Tool for Alzheimer’s Disease Research

Albasanz¹,

Castillo²,

Barrachina³

et al. 2011

The Clinical Spectrum of Alzheimer's Disease -the Charge Toward Comprehensive Diagnostic and Therapeutic Strategies

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Age-related changes in manganese superoxide dismutase activity in the cerebral cortex of senescence-accelerated prone and resistant mouse

Cited by 47 publications

References 18 publications

The senescence-accelerated mouse prone 8 as a model for oxidative stress and impaired DNA repair in the male germ line

The senescence-accelerated mouse prone 8 as a model for oxidative stress and impaired DNA repair in the male germ line

Dysfunction of astrocytes in senescence‐accelerated mice SAMP8 reduces their neuroprotective capacity

Modulation of Signal Transduction Pathways in Senescence-Accelerated Mice P8 Strain: A Useful Tool for Alzheimer’s Disease Research

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