Helmward Zollner

Bio: Helmward Zollner is an academic researcher from University of Graz. The author has contributed to research in topics: 4-Hydroxynonenal & Lipid peroxidation. The author has an hindex of 13, co-authored 24 publications receiving 7265 citations.

Reaction of Glutathione with Conjugated Carbonyls

Abstract: 1. GSH reacts with conjugated carbonyls according to the equation: GSH+R-CH=CH-COR in equilibrium R-CH(SG)-CH2-COR. The forward reaction follows second order, the reverse reaction first order kinetics. It is assumed that this reaction reflects best the ability of conjugated carbonyls to inactivate SH groups in biological systems. 2. The rate of forward reaction increases with pH approx. parallel with alphaSH. Besides OH- ions also proton donors (e.g. buffers) increase the rate. The catalytic effect of pH and buffer is interpreted in view of the reaction mechanism. 3. The equilibrium constants as well as the rate constants for forward (k1) and reverse reaction show an extreme variation depending on the carbonyl structure. Acrolein and methyl vinyl ketone (k1 = 120 and 32 mol-1 sec-1, resp.) react more rapidly than any other carbonyl to give very stable adducts (half-lives for reverse reaction 4.6 and 60.7 days, resp). Somewhat less reactive are 4-hydroxy-2-alkenals and 4-ketopentenoic acid (k1 between 1 and 3 mol-1 sec-1), but they also form very stable adducts showing half-lives between 3.4 and 19 days. All other carbonyl studied react either very slowly (e.g. citral, ethly crotonate, mesityl oxide, acrylic acid) or form very labile adducts (crotonal, pentenal, hexenal, 3-methyl-butenone). Comparing biological activities of conjugated carbonyls their reactivity towards HS (k1) and the stability of the adducts must be considered.

Metabolism of 4-Hydroxynonenal, a Cytotoxic Lipid Peroxidation Product, in Ehrlich Mouse Ascites Cells at Different Proliferation Stages

Abstract: The aldehydic lipid peroxidation product 4-hydroxynonenal (HNE) is cytotoxic at high concentrations (in the range of 100 µm); at low concentrations, it disturbs cell proliferation and exhibits genotoxic effects, and in the submicromolar range, HNE is chemotactic and stimulates phospholipase C. HNE is rapidly metabolized in eukaryotic cells. Here the metabolism of HNE was studied in suspensions of Ehrlich mouse ascites cells at different periods of the tumor age. The main products of HNE which were identified in the Ehrlich ascites cells, were glutathione-HNE-conjugate, hydroxynonenoic acid, and 1,4-dihydroxynonene. The formation of glutathione conjugates following the addition of HNE was higher in early phase cells when compared with cells in the late phase of tumor growth. That was in accordance with the increased consumption of the reduced form of glutathione. Ehrlich ascites tumor cells at the proliferation phase were able to reduce a higher amount of exogenous-added HNE, compared with cells at the stationary phase.

Nonalcoholic fatty liver disease.

Abstract: Nonalcoholic fatty liver disease (NAFLD) is present in up to one third of the general population and in the majority of patients with metabolic risk factors such as obesity and diabetes. Insulin resistance is a key pathogenic factor resulting in hepatic fat accumulation. Recent evidence demonstrates NAFLD in turn, exacerbates hepatic insulin resistance and often precedes glucose intolerance. Once hepatic steatosis is established, other factors including oxidative stress, mitochondrial dysfunction, gut-derived lipopolysaccharide and adipocytokines, may promote hepatocellular damage, inflammation and progressive liver disease. Confirmation of the diagnosis of NAFLD can usually be achieved by imaging studies, however staging the disease requires a liver biopsy. NAFLD is associated with an increased risk of all-cause death, probably because of complications of insulin resistance such as vascular disease, as well as due to cirrhosis and hepatocellular carcinoma, which occurs in a minority of patients. NAFLD is also now recognized to account for a substantial proportion of patients previously diagnosed with 'cryptogenic cirrhosis'. Diabetes, obesity and the necroinflammatory form of NAFLD known as non-alcoholic steatohepatitis, are risk factors for progressive liver disease. Current treatment relies on weight loss and exercise, although various insulin-sensitizing medications appear promising. Further research is needed to identify which patients will achieve the most benefit from therapy.

Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal.

Abstract: Lipid peroxidation can be described generally as a process under which oxidants such as free radicals attack lipids containing carbon-carbon double bond(s), especially polyunsaturated fatty acids (PUFAs). Over the last four decades, an extensive body of literature regarding lipid peroxidation has shown its important role in cell biology and human health. Since the early 1970s, the total published research articles on the topic of lipid peroxidation was 98 (1970–1974) and has been increasing at almost 135-fold, by up to 13165 in last 4 years (2010–2013). New discoveries about the involvement in cellular physiology and pathology, as well as the control of lipid peroxidation, continue to emerge every day. Given the enormity of this field, this review focuses on biochemical concepts of lipid peroxidation, production, metabolism, and signaling mechanisms of two main omega-6 fatty acids lipid peroxidation products: malondialdehyde (MDA) and, in particular, 4-hydroxy-2-nonenal (4-HNE), summarizing not only its physiological and protective function as signaling molecule stimulating gene expression and cell survival, but also its cytotoxic role inhibiting gene expression and promoting cell death. Finally, overviews of in vivo mammalian model systems used to study the lipid peroxidation process, and common pathological processes linked to MDA and 4-HNE are shown.