Disease relevance of SEPP1

• Previously, we have demonstrated dramatically reduced SeP expression in human colon adenomas [1].
• An association of SeP with the vascular endothelium, a prime target of peroxynitrite toxicity, was shown in vivo [2].
• We show that primary human astrocytes and the human astrocytoma cell line MOG-G-CCM express SeP as an unglycosylated protein, which is not secreted [3].
• Spodoptera frugiperda insect cells (IPLB-Sf21-AE) (Sf21), infected with baculovirus expression vectors during their exponential growth phase, are commonly used to produce a variety of heterologous recombinant proteins [4].
• Our data on the inhibition of selenoprotein synthesis and on repression of SeP promoter activity show that the expression of selenoproteins, especially of SeP, is influenced by acute phase reaction and pro-inflammatory reactions [5].

High impact information on SEPP1

• SeP expression in astrocytes is constitutive [3].
• Furthermore, specific downregulation of SeP expression by small interfering RNA decreases cell viability of human astrocytes and makes them more susceptible to t-BHP-induced cytotoxicity [3].
• Preincubation of astrocytes with hepatocyte-derived SeP mimicks the protective effect of low-molecular-weight selenocompounds such as sodium selenite or selenomethionine against oxidative damage, shielding astrocytes from t-BHP-induced cytotoxicity [3].
• Our results implicate an antioxidant activity of constitutively expressed SeP in selenium-deficient astrocytes, while during adequate selenium supply the enhanced protection against oxidative stress is exerted by cGPx [3].
• SeP in human plasma protects against peroxynitrite-mediated oxidation and reduces phospholipid hydroperoxide in vitro, in accordance with the presumption that it has a function as an extracellular oxidant defense [6].

Biological context of SEPP1

• Here, we have identified a complex (A)4-C-(A)4-GG-(A)8-GCT-(TC)5-(T)17 (bp -429 to bp - 477) repeat structure within the SeP promoter and we have analysed this regulatory DNA sequence with respect to polymorphisms, genomic instability and functional relevance to promoter activity [1].
• In conclusion, we characterised a complex repeat structure within the SeP promoter that may be of functional relevance to SeP gene expression [1].
• Further studies on the effect of different SeP promoter genotypes on SeP protein expression and disease susceptibility are needed [1].
• LDL were isolated from human blood plasma and oxidized with CuCl2, 2,2'-azobis(2-amidinopropane) (AAPH) or peroxynitrite in the presence or absence of SeP, using the formation of conjugated dienes as parameter for lipid peroxidation [7].
• Hepatocyte-derived SeP prevented tert-butylhydroperoxide (t-BHP)-induced oxidative cell death of Ea.hy926 cells in a similar manner as did sodium selenite, counteracting a t-BHP-induced loss of cellular membrane integrity [8].

Anatomical context of SEPP1

• SeP is expressed in the gastrointestinal tract and the liver, where its expression is downregulated by various proinflammatory cytokines (Il1beta, TGFbeta, IFNgamma) [1].
• SeP binds to heparin and cell membranes, and is associated with endothelial cells [6].
• The effect of cytokines on the expression of selenoprotein P (SeP) in the human liver cell line HepG2 was investigated [9].
• Because SeP associates with endothelial membranes, it may act in vivo as a protective factor inhibiting the oxidation of LDL by reactive oxygen species [7].
• A major fraction of the essential trace element selenium circulating in human blood plasma is present as selenoprotein P (SeP) [8].

Associations of SEPP1 with chemical compounds

• However, genistein had little or no effect on basal expression of two other ARGs, beta2-microglobulin (B2M) or selenoprotein P (SEPP1) [10].
• The human glycoprotein Selenoprotein P (SeP) contains up to 50% of plasma selenium content [1].
• A protective function of SeP in human plasma against the potent endotoxin peroxynitrite and phospholipid hydroperoxide reducing activity was demonstrated in vitro [2].
• We investigated the expression of SeP in human astrocytes and its involvement in the protection of these cells against tert-butyl hydroperoxide (t-BHP)-induced oxidative damage [3].
• The cGPx inhibitor mercaptosuccinate as well as the gamma-glutamylcysteine synthetase inhibitor buthionine sulfoximine counteracted the SeP-mediated protection, while the TR inhibitors cisplatin and auranofin had no effect [8].

Analytical, diagnostic and therapeutic context of SEPP1

• SeP of bovine serum acts as a survival-promoting factor in neuronal cell culture [2].
• RT-PCR analysis of SeP mRNA expression demonstrated an inhibition of SeP transcription to 40+/-2% of control levels after 24 h [9].
• Conversely, Western analysis revealed a dose-dependent reduction of SeP content in culture medium after treatment with transforming growth factor (TGF)-beta1 with an 1C50 of 31 pM [9].
• The latter was used for further batch and continuous cultivation of Sf21 cells in a perfused 1.4-l stirred-tank bioreactor with special attention to the oxygen requirement of these cells [4].

References