Salmon Adam B, Murakami Shin, Bartke Andrzej, Kopchick John, Yasumura Kyoko, Miller Richard A
Cellular and Molecular Biology Graduate Program, University. of Michigan School of Medicine, 1500 E. Medical Center Dr., 5316 CCGC 0940, Ann Arbor, MI 48105-0940, USA.
Am J Physiol Endocrinol Metab. 2005 Jul;289(1):E23-9. doi: 10.1152/ajpendo.00575.2004. Epub 2005 Feb 8.
Previous studies have shown that dermal fibroblast cell lines derived from young adult mice of the long-lived Snell dwarf mutant stock are resistant, in vitro, to the cytotoxic effects of H(2)O(2), cadmium, UV light, paraquat, and heat. We show here that similar resistance profiles are seen in fibroblast cells derived from a related mutant, the Ames dwarf mouse, and that cells from growth hormone receptor-null mice are resistant to H(2)O(2), paraquat, and UV but not to cadmium. Resistance to UV light, cadmium, and H(2)O(2) are similar in cells derived from 1-wk-old Snell dwarf or normal mice, and thus the resistance of cell lines derived from young adult donors reflects developmental processes, presumably hormone dependent, that take place in the first few months of life. The resistance of cells from Snell dwarf mice to these stresses does not reflect merely antioxidant defenses: dwarf-derived cells are also resistant to the DNA-alkylating agent methyl methanesulfonate. Furthermore, inhibitor studies show that fibroblast resistance to UV light is unaffected by the antioxidants ascorbic acid and N-acetyl-L-cysteine. These data suggest that postnatal exposure to altered levels of pituitary hormones leads to development of cellular resistance to oxidative and nonoxidative stressors, which are stable through many rounds of in vitro cell division and could contribute to the remarkable disease resistance of long-lived mutant mice.
先前的研究表明，源自长寿的斯内尔侏儒突变品系成年幼鼠的真皮成纤维细胞系在体外对过氧化氢、镉、紫外线、百草枯和热的细胞毒性作用具有抗性。我们在此表明，在源自相关突变体艾姆斯侏儒小鼠的成纤维细胞中也观察到类似的抗性谱，并且来自生长激素受体缺失小鼠的细胞对过氧化氢、百草枯和紫外线具有抗性，但对镉不具有抗性。1周龄的斯内尔侏儒小鼠或正常小鼠来源的细胞对紫外线、镉和过氧化氢的抗性相似，因此源自成年幼鼠供体的细胞系的抗性反映了在生命最初几个月发生的发育过程，推测是激素依赖性的。斯内尔侏儒小鼠来源的细胞对这些应激的抗性不仅仅反映抗氧化防御：侏儒来源的细胞对DNA烷化剂甲磺酸甲酯也具有抗性。此外，抑制剂研究表明，成纤维细胞对紫外线的抗性不受抗氧化剂抗坏血酸和N-乙酰-L-半胱氨酸的影响。这些数据表明，出生后暴露于改变水平的垂体激素会导致细胞对氧化和非氧化应激源产生抗性，这种抗性在多轮体外细胞分裂中保持稳定，并且可能有助于长寿突变小鼠具有显著的抗病能力。
