Increased production of oxygen free radicals is an important mechanism of endothelial dysfunction in diabetes mellitus. Our goal was to test whether adenovirus (Ad)-mediated gene transfer of copper/zinc (CuZn) or manganese superoxide dismutase (Mn SOD) improves relaxation of diabetic vessels. The aortas from 9 alloxan-induced diabetic mellitus (DM) and 16 control rabbits were used. Control and ...

Mutations in Cu, Zn superoxide dismutase (SOD1) cause a fraction of amyotrophic lateral sclerosis (ALS), which involves motoneuron degeneration, paralysis, and death. An acquired activity by mutant SOD1 is responsible for the cellular toxicity, but how mutant SOD1 kills motoneurons is unclear. In transgenic mouse models of ALS, mitochondrial degeneration occurs early, before disease onset, rais...

Cu2Zn2-superoxide dismutase (CuZn-SOD) was purified from chicken liver. The liver enzyme had a subunit Mr of 16900 and contained equimolar amounts of copper and zinc [0.260 (w/w) for each]. Aortic CuZnSOD had the same Mr as estimated by gel filtration and cross-reacted with antibodies to the liver enzyme. Both enzymes were inhibited by 1.0 mM-NaCN. Within 24-72 h after hatching, total SOD activ...

Superoxide dismutase 1 (SOD1), a ubiquitously expressed enzyme, detoxifies superoxide radicals and participates in copper homeostasis. Mutations in this enzyme have been linked to a subset of autosomal dominant cases of familial amyotrophic lateral sclerosis (FALS), a disorder characterized by selective degeneration of motor neurons. Transgenic mice expressing FALS mutant human (Hu) SOD1 at hig...

1‐Nitropyrene (1‐NP) is one of the most representative diesel exhaust‐sourced components existing in fine particulate matter (PM2.5) and a potential carcinogen. 1‐NP demonstrates significant higher cytotoxicity than its structural analogs precursor. Herein, with analog 3‐nitrofluoranthene precursor pyrene human lung epithelial cell lines are compared. An acute reactive oxygen species (ROS) acco...

Superoxide dismutase (SOD) plays a key role in the detoxification of superoxide free radicals. We evaluated the association of prostate cancer with genetic polymorphisms in SOD1 (CuZn-SOD; IVS3-251A>G), SOD2 [MnSOD; Ex2+24T>C (V16A)], and SOD3 (EC-SOD; IVS1+186C>T, Ex3-631C>G, Ex3-516C>T, and Ex3-489C>T), the three main isoforms of SOD. Prostate cancer cases (n = 1,320) from the screening arm o...

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease caused by progressive loss of upper and lower motor neurons. Mutations in superoxide dismutase 1 (SOD1) are a leading cause of ALS, responsible for up to 20% of familial cases. Although the exact mechanism by which mutant SOD1 causes disease remains unknown, multiple studies have shown that reduction of the mutant species ...

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of the motor nervous system. We show using multielectrode array and patch-clamp recordings that hyperexcitability detected by clinical neurophysiological studies of ALS patients is recapitulated in induced pluripotent stem cell-derived motor neurons from ALS patients harboring superoxide dismutase 1 (SOD1), C9orf72, and fu...

Peripherin is a type III intermediate filament protein detected in axonal spheroids associated with amyotrophic lateral sclerosis (ALS). The overexpression of peripherin induces degeneration of spinal motor neurons during aging in transgenic mice and in cultured neuronal cells derived from peripherin transgenic embryos. Here, we investigated whether peripherin is a contributor of pathogenesis i...

Mutations in the enzyme superoxide dismutase 1 (SOD1) have been linked to the neurodegenerative disease amyotrophic lateral sclerosis (ALS). In this issue of the JCI, Zhong et al. report that the endogenous anticoagulant activated protein C (APC) is able to cross the blood-spinal cord barrier in mice and signal to both neuronal and non-neuronal cells (see the related article beginning on page 3...