Masaaki Sakura

The Senescence-accelerated Mouse (SAM): A Higher Oxidative Stress and Age-dependent Degenerative Diseases Model

The SAM strain of mice is actually a group of related inbred strains consisting of a series of SAMP (accelerated senescence-prone) and SAMR (accelerated senescence-resistant) strains. Compared with the SAMR strains, the SAMP strains show a more accelerated senescence process, a shorter lifespan, and an earlier onset and more rapid progress of age-associated pathological phenotypes similar to human geriatric disorders. The higher oxidative stress status observed in SAMP mice is partly caused by mitochondrial dysfunction, and may be a cause of this senescence acceleration and age-dependent alterations in cell structure and function. Based on our recent observations, we discuss a possible mechanism for mitochondrial dysfunction resulting in the excessive production of reactive oxygen species, and a role for the hyperoxidative stress status in neurodegeneration in SAMP mice. These SAM strains can serve as a useful tool to understand the cellular mechanisms of age-dependent degeneration, and to develop clinical interventions.

Spontaneous occurrence of photoageing‐like phenotypes in the dorsal skin of old SAMP1 mice, an oxidative stress model

Skin photoageing is a complex, multifactorial process and both intrinsic and extrinsic factors may contribute to its pathogenesis. The ultraviolet‐irradiated hairless mouse has been used as an animal model for photoageing, but this model mimics only the ‘extrinsic’ aspects. Here, we show that skin from old SAMP1 mice, a model for higher oxidative stress and senescence acceleration, exhibited histological and gene expression changes similar to those in human photoaged skin without ultraviolet irradiation. These changes include an increase in elastic fibre and glycosaminoglycan histologically, an upregulation of several proinflammatory cytokines and matrix metalloproteinases, and an increase in lipid peroxide. We propose that SAMP1 mice are a spontaneous animal model for photoageing caused by an exaggerated intrinsic mechanism, namely, higher oxidative status. This mouse model is useful to explore the link between oxidative stress and photoageing, and to evaluate the efficacy of antioxidants.

Antioxidative Effects of Cherry Leaves Extract on tert-Butyl Hydroperoxide-Mediated Cytotoxicity Through Regulation of Thioredoxin-2 Protein Expression Levels

Components of cherry trees have been used as traditional herbal remedies for various diseases. These components are known to possess antioxidative effects. However, the mechanisms underlying cherry tree component-mediated antioxidative effects remain largely unknown. This study focused on cherry leaves extract (CLE) and examined the mechanism underlying the effect of CLE on tert-butyl hydroperoxide (t-BOOH)-induced melanocytic cell death with DNA damage. Interestingly, CLE prevented t-BOOH-induced cell death with reduction in DNA damage, p38 kinase activation, and reactive oxygen species (ROS) production. CLE-mediated suppression of cell death with reduction of DNA damage, p38 kinase activity and ROS production was prevented by a thioredoxin (Trx) system inhibitor but not by a glutathione (GSH) system inhibitor. Finally, data showed that CLE prevented t-BOOH-induced reduction of Trx2 but not Trx1 and Trx reductases (TrxR1 and TrxR2) protein expression. Thus, our results suggest that CLE prevents t-BOOH-induced reduction in Trx2 expression, promotion of ROS production, activation of p38 kinase, and increase in DNA damage and that it protects against cell death.

Cigarette Smoke Induce Alteration of Structure and Function in Alveolar Macrophages

 Abstract—Cigarette smoke (CS) is released into the atmosphere, and impact lung health in non-smoker but not smoker. CS is inhaled into the lung by respiration and affects alveolar macrophages (AM). AM play an important role of immune system in the lung. In this study, we investigated the effect of CS on DNA damage and immune function in AM. The number of AM was significantly increased in CS exposed mice compared with non CS-exposed mice. Expressions of CD11b, TLR-2 and CD14 on AM were significantly inhibited in CS exposed mice but not CD16. Phagocytic activity of AM was significantly inhibited in CS exposed mice. Both of tail moment and tail length of AM as indicator of DNA damage were significantly increased in CS exposed mice. CS was a risk factor for DNA damage of AM and induced inhibition of immunological functions in AM mediated with DNA damage. These results suggest that changes of intracellular structure, inhibition of phagocytosis and TLR expression and induced-DNA damage of AM by CS may result in easily infection of bacteria or virus and carcinogenesis.