Cu,Zn-superoxide dismutase increases toxicity of mutant and zinc-deficient superoxide dismutase by enhancing protein stability.

ABSTRACT: When replete with zinc and copper, amyotrophic lateral sclerosis (ALS)-associated mutant SOD proteins can protect motor neurons in culture from trophic factor deprivation as efficiently as wild-type SOD. However, the removal of zinc from either mutant or wild-type SOD results in apoptosis of motor neurons through a copper- and peroxynitrite-dependent mechanism. It has also been shown that motor neurons isolated from transgenic mice expressing mutant SODs survive well in culture but undergo apoptosis when exposed to nitric oxide via a Fas-dependent mechanism. We combined these two parallel approaches for understanding SOD toxicity in ALS and found that zinc-deficient SOD-induced motor neuron death required Fas activation, whereas the nitric oxide-dependent death of G93A SOD-expressing motor

SUBMITTER: Garner MA 

PROVIDER: S-EPMC2962488 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature