Autophagy upregulation and loss of NF-κB in oxidative stress-related immunodeficient SAMP8 mice

被引:23
作者
Caballero, Beatriz [1 ]
Vega-Naredo, Ignacio [1 ]
Sierra, Veronica [1 ,2 ]
DeGonzalo-Calvo, David [1 ]
Medrano-Campillo, Pablo [3 ]
Guerrero, Juan M. [3 ]
Tolivia, Delio [1 ]
Rodriguez-Colunga, Maria J. [1 ]
Coto-Montes, Ana [1 ]
机构
[1] Univ Oviedo, Dept Morfol & Biol Celular, Fac Med, E-33006 Oviedo, Spain
[2] SERIDA, Villaviciosa, Spain
[3] Univ Seville, Hosp Virgen de la Macarena, Dept Bioquim Med & Biol Mol, Seville, Spain
关键词
Aging; Apoptosis; Autophagy; Oxidative stress; NF-kappa B; SENESCENCE-ACCELERATED MICE; DROSOPHILA-MELANOGASTER; MOLECULAR-MECHANISMS; REACTIVE OXYGEN; MELATONIN; DAMAGE; BRAIN; LEVEL; NEURODEGENERATION; DEGRADATION;
D O I
10.1016/j.mad.2009.09.001
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Aged spleens from senescence-accelerated prone mice 8 (SAMP8) and senescence-accelerated resistant mice 1 (SAMR1) were examined to determine whether sex or melatonin had an effect on oxidative stress-related immune impairments. We observed that the immunosenescence of SAMP8 mice was associated with a redox imbalance, leading to an age-related increase in oxidative damage, resulting from a decrease in antioxidant defense and protease activity. Moreover, increased apoptotic cell death, a decrease in proliferative activity and the loss of NF-kappa B activation were also related to the immunodeficiency seen in SAMP8 compared to SAMR1 mice. Females demonstrated higher oxidative stress-related alterations in the immune response, and subsequent, melatonin treatment provided the best protective effects. Pathways involved in autophagy were upregulated in SAMP8 as an adaptive response to oxidative stress, in an attempt to rescue the cell from increased apoptosis and age-related immunodeficiency. However, the NF-kappa B signaling and autophagic processes were unaffected by treatment with melatonin. Therefore, we propose a key role for NF-kappa B signaling and autophagy in the oxidative stress-related immunosenescent spleens of SAMP8 mice. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:722 / 730
页数:9
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