Thioredoxin family proteins in physiology and disease

Proteins of the thioredoxin (Trx) family are ubiquitously expressed oxidoreductases. They use cysteinyl residues within their active site to modify substrate proteins posttranslationally by reduction/oxidation reactions or de-/glutathionylation. They play a crucial role in regulating cellular functions such as proliferation, differentiation and apoptosis. This thesis entitled “Thioredoxin family proteins in physiology and disease” focusses on these proteins, i.e. the Trx systems, the glutaredoxin (Grx) systems and the peroxiredoxins (Prxs). Because descriptions of cellular functions of redoxins are rare, we aimed at identifying new interaction partners and functions under physiological and hypoxic conditions in various cell culture and animal models. This thesis emphasizes the concept of compartmentalised redox signaling and demonstrates not only the complexity of the Trx family proteins, but the species-, tissue- and cell type-specific responses to oxygen deprivation and the distinct contribution of the redoxins to controling the fate of a cell. In detail: - Human, mitochondrial Grx2 is an electron donor for Prx3. - Vertebrate Grx3 (human and zebrafish) is involved in iron regulation. - Trx family proteins showed a tissue- and cell type-specific expression and distribution in the rat CNS and responded tissue- and cell type-specific to oxygen deprivation in numerous cell lines and models for perinatal asphyxia, renal ischemia/reperfusion (I/R) injury and transplantation of pancreatic β-cells. (compare to summary of the thesis