Autophagy upregulation and loss of NF-kappaB in oxidative stress-related immunodeficient SAMP8 mice.
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-kappaB 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-kappaB signaling and autophagic processes were unaffected by treatment with melatonin. Therefore, we propose a key role for NF-kappaB signaling and autophagy in the oxidative stress-related immunosenescent spleens of SAMP8 mice.
Caballero
Beatriz
B
Departamento de Morfología y Biología Celular, Facultad de Medicina, Universidad de Oviedo, C/Julián Clavería s/n, 33006 Oviedo, Spain.
Vega-Naredo
Ignacio
I
Sierra
Verónica
V
DeGonzalo-Calvo
David
D
Medrano-Campillo
Pablo
P
Guerrero
Juan M
JM
Tolivia
Delio
D
Rodríguez-Colunga
María J
MJ
Coto-Montes
Ana
A
D000375:Aging / Q000276:immunology*; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D017209:Apoptosis; D001343:Autophagy / Q000187:drug effects / Q000276:immunology*; D002374:Catalase / Q000378:metabolism; D002401:Cathepsin B / Q000378:metabolism; D002402:Cathepsin D / Q000378:metabolism; D005260:Female; D008297:Male; D008550:Melatonin / Q000008:administration & dosage; D051379:Mice; D016328:NF-kappa B / Q000032:analysis / Q000502:physiology*; D018384:Oxidative Stress / Q000276:immunology*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D044094:Receptors, Melatonin / Q000032:analysis; D012737:Sex Factors; D015398:Signal Transduction / Q000187:drug effects; D013154:Spleen / Q000201:enzymology / Q000276:immunology
D000975:Antioxidants; D016328:NF-kappa B; D018809:Proliferating Cell Nuclear Antigen; D044094:Receptors, Melatonin; D002374:Catalase; D002401:Cathepsin B; D002402:Cathepsin D; D008550:Melatonin