Biomedical subjects

Kerstin Schnurr

Publications and source records attributed to Kerstin Schnurr.

3 recordsLinked to original sources

PubMed2005

Recognition of malignant processes with neural nets from ESR spectra of serum albumin.

Cancer diseases are the focus of intense research due to their frequent occurrence. It is known from the literature that serum proteins are changed in the case of malignant processes. Changes of albumin conformation, transport efficiency, and binding characteristics can be determined by electron spin resonance spectroscopy (ESR). The present study analysed the binding/dissociation function of albumin with an ESR method using 16-doxyl stearate spin probe as reporter molecule and ethanol as modifier of hydrophobic interactions. Native and frozen plasma of healthy donors (608 samples), patients with malignant diseases (423 samples), and patients with benign conditions (221 samples) were analysed. The global specificity was 91% and the sensitivity 96%. In look-back samples of 27 donors, a malignant process could be detected up to 30 months before clinical diagnosis. To recognise different entities of malignant diseases from the ESR spectra, Artificial neural networks were implemented. For 48 female donors with breast cancer, the recognition specificity was 85%. Other carcinoma entities (22 colon, 18 prostate, 12 stomach) were recognised with specificities between 75% and 84%. Should these specificity values be reproduced in larger studies, the described method could be used as a new specific tumour marker for the early detection of malignant processes. Since transmission of cancer via blood transfusion cannot be excluded as yet, the described ESR method could also be used as a quality test for plasma products.

Adolescent↗

PubMed2004

Inhibition of basal and interleukin-1-induced VCAM-1 expression by phospholipid hydroperoxide glutathione peroxidase and 15-lipoxygenase in rabbit aortic smooth muscle cells.

Cytokines or hydroperoxides upregulate cell adhesion molecules (CAM) in early stages of atherosclerosis. VCAM-1 expression was therefore investigated in rabbit aortic smooth muscle cells (SMC) stably transfected either with phospholipid hydroperoxide glutathione peroxidase (PHGPx; SMCPHGPx) as a hydroperoxide-reducing enzyme or with 15-lipoxygenase (15-LOX; SMCLOX) as a hydroperoxide-producing enzyme. Transfected cells showed up to 3-fold enhanced PHGPx and a marked LOX activity, respectively, that was absent in controls. Intracellular hydroperoxides were 6-fold higher in SMCLOX than in SMC or SMCPHGPx. Intracellular protein thiols were decreased by 50 and 90% in SMCPHGPx and SMCLOX, respectively. Glutathione mixed disulfides were tentatively increased from SMC via SMCPHGPx to SMCLOX, accordingly. Thiol reduction with tris(2-carboxyethyl)phosphine completely restored protein thiols in SMCPHGPx, whereas in SMCLOX only 60% of control values were recovered. Basal VCAM-1 mRNA levels were decreased by 50% in SMCPHGPx and 75% in SMCLOX. VCAM-1-inducibility was abrogated in SMCLOX but not in SMCPHGPx. Accordingly, NFkappaB-driven reporter gene activation by IL-1 was unaffected in SMCPHGPx but abolished in SMCLOX. The data confirm that PHGPx overexpression dampens CAM expression either by lowering stimulatory hydroperoxides or by using hydroperoxides for protein modification. But hydroperoxides, when constitutively overproduced as in SMCLOX, inhibit CAM expression and render cells refractory to IL-1 stimulation likely due to oxidation of protein thiols of the signaling system.

Animals↗

PubMed2003

Selenium-dependent enzymes in endothelial cell function.

Glutathione peroxidases and thioredoxin reductases are the main selenoproteins expressed by endothelial cells. These enzymes reduce hydroperoxides, their role in endothelial cell physiology, however, by far exceeds prevention of oxidative damage. Reactive oxygen and nitrogen species, especially superoxide, hydroperoxides, and nitric oxide, are crucial signaling molecules in endothelial cells. Their production is regulated by vascular NAD(P)H oxidases and the endothelial nitric oxide synthase. Their metabolism and physiological functions are coordinated by glutathione peroxidases and the thioredoxin/thioredoxin reductase system. Endothelial selenoproteins are involved in the regulation of the vascular tone by maintaining the superoxide anion/nitric oxide balance, of cell adhesion by controlling cell adhesion molecule expression, of apoptosis via inhibition/activation of apoptosis signal-regulating kinase-1, and of eicosanoid production by controlling the activity of cyclooxygenases and lipoxygenases. Accordingly, they regulate inflammatory processes and atherogenesis. The underlying mechanisms are various and differ between individual selenoproteins. Scavenging of hydroperoxides not only prevents oxidative damage, but also interferes with signaling cascades and enzymes involved. Modulation of proteins by hydroperoxide-driven thiol/disulfide exchange is a novel mechanism that needs to be further investigated. A better understanding of the complex interplay of selenoproteins in regulating endothelial cell functions will help to develop a rationale for an improvement of health by an optimum selenium supply.

Animals↗