Overexpression of copper-zinc superoxide dismutase in trisomy 21

Abstract

Down's syndrome (DS), the most frequent of congenital birth defects, results from the trisomy of chromosome 21 in all cells of affected patients. This disease is characterized by developmental anomalies, mental retardation and features of rapid aging, particularly in the brain, where the occurrence of Alzheimer's disease is observed in trisomy 21 patients over the age of 35. Copper-zinc superoxide dismutase (CuZnSOD) is one of the proteins encoded by chromosome 21 (21q22.1). As a consequence of gene dosage excess, CuZnSOD activity is increased by 50% in all DS tissues. This work reports the SOD activity of a population of DS patients with complete trisomy 21, partial trisomy 21, translocations and mosaicism, in order to confirm the gene dosage effect of SOD on the clinical features of DS, and to help to establish which is the critical region of chromosome 21 in DS. CuZnSOD was measured in red blood cells using the Minami and Yoshikawa method. In the population with complete trisomy 21, SOD activity was increased by 42%; in the population with partial trisomy 21, translocations and mosaicism, SOD activity was normal. In the population diagnosed as DS, but not karyotyped, SOD activity was increased by 28%. No differences between sexes or among ages were found. We conclude that the 21q22.1 segment is not the critical region responsible for DS, as we have found normal SOD activity in patients with the clinical features of DS.

Overexpression of human copper,zinc-superoxide dismutase (SOD1) prevents postischemic injury

“…Although numerous studies have been performed with administration of exogenous SOD1 this 32-kDa protein is not readily internalized within cells, and in the setting of myocardial reperfusion injury variable protective effects were observed (6,(35)(36)(37)(38). There have been reports that increased SOD1 expression can have deleterious effects, and it has even been suggested that modest increases in expression may trigger the abnormalities seen in Down's syndrome (16). With admin- istration of exogenous SOD1 to ischemic tissues it has been reported that dose-dependent toxicity may also occur (39).…”

“…Increased peroxidase activity has been advanced as a possible cause of the familial form of the neurodegenerative disease amyotrophic lateral sclerosis, FALS (9)(10)(11)(12)(13)(14)(15). It has also been suggested that Down's syndrome, trisomy 21, is caused by a 50% increase in SOD1 expression (16). Thus, fundamental questions have been raised regarding the effects of altered SOD1 expression on cellular function and development.…”

Early thymic T cell development in young transgenic mice overexpressing human Cu/Zn superoxide dismutase, a model of Down syndrome

“…. The hSOD1 gene is located on chromosome 21 in q22.1 and the SOD1 enzymatic activity is consequently over-expressed in trisomy 21, or Down's syndrome (DS) persons [1,2]. DS is associated with humoral and cellular immunological abnormalities [3][4][5][6], which are more pronounced in aged patients [7,8].…”

Nutritional supplementation in Down syndrome: theoretical considerations and current status

“…One of these genes codes for the enzyme SOD 6 . As expected from the gene dose effect, many studies have found an increase in SOD activity of 50% or Annotation more in various tissues of individuals with DS [8][9][10][11][12][13][14][15][16] .…”