Superoxide Dismutase 3

The content of SOD3 in most tissues is very small and amounts to 1–5% of the total level of superoxide dismutases, but the blood vessels, lungs, and, to a lesser extent, the heart, are characterized by an increased concentration of SOD3. ^[2] In the vascular system, SOD3 is attached to the heparan sulfate proteoglycans of the epithelium. When examining the human eye , a high content of SOD3 was noted in the cornea and sclera . ^[3]

It has been shown that the production of SOD3 in human fibroblasts and muscle cells is regulated indirectly by cytokines and growth factors, and not by oxidative stress itself . ^[4] According to one group of researchers, transcription factors sp1 and sp3 can regulate SOD3 expression. ^{[5] [6]}

According to animal studies, exercise causes a surge in SOD3 expression. ^[7]

In one study, administration of ACE inhibitors or angiotensin receptor antagonists by individuals with coronary artery disease significantly increased SOD3 expression. ^[eight]

Keratoconus

According to one study conducted on sections of the cornea taken during keratoplasty , with keratoconus, the level of SOD3 is reduced in the central part of the cornea by about half the norm, even if this section of the cornea was previously transplanted from a person who did not suffer from keratoconus during life. Moreover, in all corneas, SOD3 was distributed unevenly, with a minimum concentration in the center. ^[9] One article notes that SOD3 mRNA levels during keratoconus are unchanged. ^[10] Another publication reported that a culture of keratocytes (corneal fibroblasts ) taken from stroma of the cornea , taken with keratoplasty in patients with keratoconus, under the influence of the pro-inflammatory cytokine interleukin 1 ( alpha ) shows a continuing decrease in SOD3 levels. Control cultures of keratocytes from healthy corneas and corneas affected by bullous keratopathy , on the contrary, gradually increased the production of SOD3 after the initial drop in enzyme levels when IL1-alpha was added. ^[eleven]

The role of polymorphism ARG213GLY

In one 1992 study, 6-15% of healthy subjects showed a 10-15-fold increase in serum SOD3 levels above the average. ^[12] Later, such groups were identified in both the Swedish, ^[13] and Japanese populations; ^[14] at the same time, a substitution C-> G at position 760 ( single nucleotide polymorphism ARG213GLY) was noted in cDNA . In a 2004 study, this polymorphism was associated with an increased (approximately 1.5-fold) risk of coronary heart disease and ischemic cerebrovascular disease. ^[15] This is explained not by impaired enzymatic activity, but by the reduced binding of SOD3 _R213G to the surface of cells, including endothelial ones: the variation changes the structure of its heparin binding domain and, accordingly, the ability to bind to heparan sulfate proteoglycans . ^[sixteen]

Animal Research

According to one study, transgenic mice with increased SOD3 expression differ in old age by improved long-term potentiation in the hippocampus compared to conventional mice, are better trained in motor tasks in tests involving the cerebellum , and are oriented in space. At a young age, they had a deteriorated ability to contextual learning, but these differences were somewhat leveled out with aging. ^[17]

Homozygous knockout of the SOD3 gene does not reduce the lifespan of mice or their ability to reproduce. ^[18]