| First Author | Tirosh O | Year | 2005 |
| Journal | Mech Ageing Dev | Volume | 126 |
| Issue | 12 | Pages | 1262-73 |
| PubMed ID | 16139868 | Mgi Jnum | J:103672 |
| Mgi Id | MGI:3610601 | Doi | 10.1016/j.mad.2005.07.003 |
| Citation | Tirosh O, et al. (2005) Long-lived alphaMUPA transgenic mice show reduced SOD2 expression, enhanced apoptosis and reduced susceptibility to the carcinogen dimethylhydrazine. Mech Ageing Dev 126(12):1262-73 |
| abstractText | Calorie restriction (CR) extends the life span of various species through mechanisms that are as yet unclear. Recently, we have reported that mitochondrion-mediated apoptosis was enhanced in alphaMUPA transgenic mice that spontaneously eat less and live longer compared with their wild-type (WT) control mice. To understand the molecular mechanisms underlying the increased apoptosis, we compared alphaMUPA and WT mice for parameters associated with SOD2 (MnSOD), a mitochondrial antioxidant enzyme that converts superoxide radicals into H(2)O(2) and is also known to inhibit apoptosis. The SOD2-related parameters included the levels of SOD2 mRNA, immunoreactivity and enzymatic activity in the liver, lipid oxidation and aconitase activity in isolated liver mitochondria, and the sensitivity of the mice to paraquat, an agent that elicits oxidative stress. In addition, we compared the mice for the levels of SOD2 mRNA after treatment with bacterial lipopolysaccharides (LPS), and for the DNA binding activity of NFkappaB as a marker for the inflammatory state. We extended SOD2 determination to the colon, where we also examined the formation of pre-neoplastic aberrant crypt foci (ACF) following treatment with dimethylhydrazine (DMH), a colonic organotypic carcinogen. Overall, alphaMUPA mice showed reduced basal levels of SOD2 gene expression and activity concomitantly with reduced lipid oxidation, increased aconitase activity and enhanced paraquat sensitivity, while maintaining the capacity to produce high levels of SOD2 in response to the inflammatory stimulus. alphaMUPA mice also showed increased resistance to DMH-induced pre-neoplasia. Collectively, these data are consistent with a model, in which an optimal fine-tuning of SOD2 throughout a long-term regimen of reduced eating could contribute to longevity, at least in the alphaMUPA mice. |
