Exogenous manganous ion at millimolar levels rescues all known dioxygen-sensitive phenotypes of yeast lacking CuZnSOD

Exogenous manganous ion at millimolar levels rescues all known dioxygen-sensitive phenotypes of yeast lacking CuZnSOD
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DOI:
10.1007/s00775-005-0044-y
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发表时间:
2005-12-01
影响因子:
3
通讯作者:
Valentine, JS
Valentine, JS
中科院分区:
化学3区
文献类型:
--
作者:
Sanchez, RJ;Srinivasan, C;Valentine, JS

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缺乏铜锌超氧化物歧化酶(sod1 Delta)的酵母表现出广泛的表型,其中许多表型可以通过在高水平离子锰存在下生长来挽救。我们对锰对野生型和 sod1 Delta 酵母的影响进行了全面调查,发现 5 mM Mn2+ 挽救了所有已知的与生长相关的表型,例如空气中生长缓慢、温度敏感性、特定氨基酸营养缺陷型、高氧条件下不生长、不可发酵碳源中生长不良以及稳定期存活率降低。与铁相关的表型——电子顺磁共振可检测到的(“游离”)铁升高、乌头酸酶活性降低、液泡破碎——以及锌敏感性也得到了挽救。当酵母在 MnCl2 存在下生长时,锰超氧化物歧化酶的活性保持不变或降低,这表明这种替代性超氧化物歧化酶的诱导并不是原因。与 MnCl2 处理相反,在生长培养基中添加两种含锰的超氧化物歧化酶模拟化合物并没有对 sod1 Delta 酵母生长提供任何拯救,而是在微摩尔浓度下具有 sod1 Delta 选择性抑制作用。讨论了离子锰可以实现这种救援而模拟化合物则不能的机制。
Yeasts lacking copper-zinc superoxide dismutase (sod1 Delta) exhibit a broad range of phenotypes, many of which can be rescued by growth in the presence of high levels of ionic manganese. We undertook a comprehensive survey of the effects of manganese on wild-type and sod1 Delta yeasts and found that 5 mM Mn2+ rescued all known growth-related phenotypes, such as slow growth in air, temperature sensitivity, specific amino acid auxotrophies, no growth in high oxygen, poor growth in nonfermentable carbon sources, and decreased stationary-phase survival. Iron-related phenotypes-elevated electron paramagnetic resonance detectable ("free") iron, decreased aconitase activity, and fragmenting vacuoles-as well as zinc sensitivity were also rescued. The activity of manganese superoxide dismutase remained constant or was reduced when the yeasts were grown in the presence of MnCl2, indicating that induction of this alternative superoxide dismutase is not the explanation. In contrast to MnCl2 treatment, addition of two manganese-containing superoxide dismutase mimetic compounds to the growth medium did not provide any rescue of sod1 Delta yeast growth but rather had an sod1 Delta-selective inhibitory effect at micromolar concentrations. Mechanisms by which ionic manganese can effect this rescue, while the mimetic compounds do not, are discussed.