TY  - JOUR
AB  - NAFLD is a common disease in Western society and ranges from steatosis to steatohepatitis and to end-stage liver disease. The molecular mechanisms that cause the progression of steatosis to severe liver damage are not fully understood. One suggested mechanism involves the oxidation of biomolecules by mitochondrial ROS which initiates a vicious cycle of exacerbated mitochondrial dysfunction and increased hepatocellular oxidative damage. This may ultimately pave the way for hepatic inflammation and liver failure. This review updates our current understanding of mitochondria-derived oxidative stress in the progression of NAFLD.
AU  - Simões, I.C.M.*
AU  - Fontes, A.
AU  - Pinton, P.*
AU  - Zischka, H.
AU  - Wieckowski, M.R.*
C1  - 52656
C2  - 42426
CY  - Oxford
SP  - 93-99
TI  - Mitochondria in non-alcoholic fatty liver disease.
JO  - Int. J. Biochem. Cell Biol.
VL  - 95
PB  - Pergamon-elsevier Science Ltd
PY  - 2018
SN  - 1357-2725
ER  - 

TY  - JOUR
AB  - In mitochondria, copper is a Janus-faced trace element. While it is the essential cofactor of the mitochondrial cytochrome c oxidase, a surplus of copper can be highly detrimental to these organelles. On the one hand, mitochondria are strictly dependent on adequate copper supply for proper respiratory function, and the molecular mechanisms for metalation of the cytochrome c oxidase have been largely characterized. On the other hand, copper overload impairs mitochondria and uncertainties exist concerning the molecular mechanisms for mitochondrial metal uptake, storage and release. The latter issue is of fundamental importance in Wilson disease, a genetic disease characterized by dysfunctional copper excretion from the liver. Prime consequences of the progressive copper accumulation in hepatocytes are increasing mitochondrial biophysical and biochemical deficits. Focusing on this two-sided aspect of mitochondrial copper, we review mitochondrial copper homeostasis but also the impact of excessive mitochondrial copper in Wilson disease.
AU  - Zischka, H.
AU  - Einer, C.
C1  - 53924
C2  - 45097
CY  - The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, England
SP  - 71-75
TI  - Mitochondrial copper homeostasis and its derailment in Wilson disease.
JO  - Int. J. Biochem. Cell Biol.
VL  - 102
PB  - Pergamon-elsevier Science Ltd
PY  - 2018
SN  - 1357-2725
ER  - 

TY  - JOUR
AB  - Fibroblasts are extracellular matrix-producing cells in the lung. Fibroblast activation by transforming growth factor-beta leads to myofibroblast-differentiation and increased extracellular matrix deposition, a hallmark of pulmonary fibrosis. While fibroblast function with respect to migration, invasion, and extracellular matrix deposition has been well-explored, little is known about the surface proteome of lung fibroblasts in general and its specific response to fibrogenic growth factors, in particular transforming growth factor-beta. We thus performed a cell-surface proteome analysis of primary human lung fibroblasts in presence/absence of transforming growth factor-beta, followed by characterization of our findings using FACS analysis, Western blot, and siRNA-mediated knockdown experiments. We identified 213 surface proteins significantly regulated by transforming growth factor-beta, platelet derived growth factor receptor-alpha being one of the top down-regulated proteins. Transforming growth factor beta-induced downregulation of platelet derived growth factor receptor-alpha induced upregulation of platelet derived growth factor receptor-beta expression and phosphorylation of Akt, a downstream target of platelet derived growth factor signaling. Importantly, collagen type V expression and secretion was strongly increased after forced knockdown of platelet derived growth factor receptor-alpha, an effect that was potentiated by transforming growth factor-beta. We therefore show previously underappreciated cross-talk of transforming growth factor-beta and platelet derived growth factor signaling in human lung fibroblasts, resulting in increased extracellular matrix deposition in a platelet derived growth factor receptor-alpha dependent manner. These findings are of particular importance for the treatment of lung fibrosis patients with high pulmonary transforming growth factor-beta activity.
AU  - Heinzelmann, K.
AU  - Noskovicova, N.
AU  - Merl-Pham, J.
AU  - Preissler, G.*
AU  - Winter, H.*
AU  - Lindner, M.*
AU  - Hatz, R.A.*
AU  - Hauck, S.M.
AU  - Behr, J.*
AU  - Eickelberg, O.
C1  - 47978
C2  - 39803
CY  - Oxford
SP  - 44-59
TI  - Surface proteome analysis identifies platelet derived growth factor receptor-alpha as a critical mediator of transforming growth factor-beta-induced collagen secretion.
JO  - Int. J. Biochem. Cell Biol.
VL  - 74
PB  - Pergamon-elsevier Science Ltd
PY  - 2016
SN  - 1357-2725
ER  - 

TY  - JOUR
AB  - For more than 50 years, reactive oxygen species have been considered as harmful agents, which can attack proteins, lipids or nucleic acids. In order to deal with reactive oxygen species, there is a sophisticated system developed in mitochondria to prevent possible damage. Indeed, increased reactive oxygen species levels contribute to pathomechanisms in several human diseases, either by its impaired defense system or increased production of reactive oxygen species. However, in the last two decades, the importance of reactive oxygen species in many cellular signaling pathways has been unraveled. Homeostatic levels were shown to be necessary for correct differentiation during embryonic expansion of stem cells. Although the mechanism is still not fully understood, we cannot only regard reactive oxygen species as a toxic by-product of mitochondrial respiration anymore.
AU  - Holzerova, E.
AU  - Prokisch, H.
C1  - 43261
C2  - 36370
CY  - Oxford
SP  - 16-20
TI  - Mitochondria: Much ado about nothing? How dangerous is reactive oxygen species production?
JO  - Int. J. Biochem. Cell Biol.
VL  - 63
PB  - Pergamon-elsevier Science Ltd
PY  - 2015
SN  - 1357-2725
ER  - 

TY  - JOUR
AB  - Idiopathic pulmonary fibrosis (IPF) is the most common and fatal form of idiopathic interstitial pneumonia. MicroRNAs (miRNAs), short, single-stranded RNAs that regulate protein expression in a post-transcriptional manner, have recently been demonstrated to contribute to IPF pathogenesis. We have previously identified WNT1-inducible signaling pathway protein 1 (WISP1) as a highly expressed pro-fibrotic mediator in IPF, but the underlying mechanisms resulting in increased WISP1 expression, remain elusive. Here, we investigated whether WISP1 is a target of miRNA regulation. We applied a novel supervised machine learning approach, which predicted miR-30a/d and miR-92a target sites in regions of the human WISP1 3'UTR preferentially bound by the miRNA ribonucleoprotein complex. Both miRNAs were decreased in IPF samples, whereas WISP1 protein was increased. We demonstrated further that transforming growth factor (TGF)-β1-induced WISP1 expression in primary lung fibroblasts in vitro and lung homogenates in vivo. Notably, miR-30a and miR-92a reversed TGF-β1-induced WISP1 mRNA expression in lung fibroblasts. Moreover, miR-92a inhibition increased WISP1 protein expression in lung fibroblasts. An inverse relationship for WISP1 and miR-92a was found in a TGF-β1 dependent lung fibrosis model in vivo. Finally, we found significantly increased WISP1 expression in primary IPF fibroblasts, which negatively correlated with miR-92a level ex vivo. Altogether, our findings indicate a regulatory role of miR-92a for WISP1 expression in pulmonary fibrosis.
AU  - Berschneider, B.
AU  - Ellwanger, D.C.
AU  - Baarsma, H.A.
AU  - Thiel, C.T.
AU  - Shimbori, C.*
AU  - White, E.S.*
AU  - Kolb, M.*
AU  - Neth, P.*
AU  - Königshoff, M.
C1  - 31663
C2  - 34715
CY  - Oxford
SP  - 432-441
TI  - miR-92a regulates TGF-β1-induced WISP1 expression in pulmonary fibrosis.
JO  - Int. J. Biochem. Cell Biol.
VL  - 53
PB  - Pergamon-elsevier Science Ltd
PY  - 2014
SN  - 1357-2725
ER  - 

TY  - JOUR
AB  - High blood glucose levels are the main feature of diabetes. However, the underlying mechanism linking high glucose concentration to diabetic complications is still not fully elucidated, particularly with regard to human physiology. Excess of glucose is likely to trigger a metabolic response depending on the cell features, activating deleterious pathways involved in the complications of diabetes. In this study, we aim to elucidate how acute and prolonged hyperglycaemia alters the biology and metabolism in human fibroblasts and endothelial cells. We found that hyperglycaemia triggers a metabolic switch from oxidative phosphorylation to glycolysis that is maintained over prolonged time. Moreover, osmotic pressure is a major factor in the early metabolic response, decreasing both mitochondrial transmembrane potential and cellular proliferation. After prolonged exposure to hyperglycaemia we observed decreased mitochondrial steady-state and uncoupled respiration, together with a reduced ATP/ADP ratio. At the same time, we could not detect major changes in mitochondrial transmembrane potential and reactive oxygen species. We suggest that the physiological and metabolic alterations observed in healthy human primary fibroblasts and endothelial cells are an adaptive response to hyperglycaemia. The severity of metabolic and bioenergetics impairment associated with diabetic complications may occur after longer glucose exposure or due to interactions with cell types more sensitive to hyperglycaemia.
AU  - Moruzzi, N.
AU  - Del Sole, M.*
AU  - Fato, R.*
AU  - Gerdes, J.M.
AU  - Berggren, P.O.*
AU  - Bergamini, C.*
AU  - Brismar, K.*
C1  - 31540
C2  - 34539
CY  - Oxford
SP  - 66-76
TI  - Short and prolonged exposure to hyperglycaemia in human fibroblasts and endothelial cells: Metabolic and osmotic effects.
JO  - Int. J. Biochem. Cell Biol.
VL  - 53
PB  - Pergamon-elsevier Science Ltd
PY  - 2014
SN  - 1357-2725
ER  - 

TY  - JOUR
AB  - WISP1 is a secreted, matricellular protein allocated to the CCN protein family. The CCN protein family consists of six, modular structured, secreted proteins. WISP1 is mainly expressed during organ development and under diseased conditions, such as fibrosis or cancer. Its expression is associated with proliferation, cytoprotection, as well as extracellular matrix production, thereby representing a highly attractive therapeutical target for future applications.
AU  - Berschneider, B.
AU  - Königshoff, M.
C1  - 6369
C2  - 28733
SP  - 306-309
TI  - WNT1 inducible signaling pathway protein 1 (WISP1): A novel mediator linking development and disease.
JO  - Int. J. Biochem. Cell Biol.
VL  - 43
IS  - 3
PB  - Elsevier
PY  - 2011
SN  - 1357-2725
ER  - 

TY  - JOUR
AU  - Beck, V.*
AU  - Herold, H.*
AU  - Benge, A.*
AU  - Luber, B.*
AU  - Hutzler, P.
AU  - Tschesche, H.*
AU  - Kessler, H.*
AU  - Schmitt, M.*
AU  - Geppert, H.-D.*
AU  - Reuning, U.*
C1  - 2634
C2  - 22829
SP  - 590-603
TI  - ADAM15 decreases integrin alphavß3/vitronectin-mediated ovarian cancer cell adhesion and motility in an RGD-dependent fashion.
JO  - Int. J. Biochem. Cell Biol.
VL  - 37
PY  - 2005
SN  - 1357-2725
ER  - 

TY  - JOUR
AU  - Holmer, S.R.*
AU  - Bickeböller, H.
AU  - Hengstenberg, C.*
AU  - Rohlmann, F.*
AU  - Engel, B.
AU  - Löwel, H.
AU  - Mayer, B.*
AU  - Erdmann, J.*
AU  - Baier, C.*
AU  - Klein, G.*
AU  - Riegger, G.A.J.*
AU  - Schunkert, H.*
C1  - 9644
C2  - 21571
SP  - 955-962
TI  - Angiotensin converting enzyme gene polymorphism and myocardial infarction a large association and linkage study. 
JO  - Int. J. Biochem. Cell Biol.
VL  - 35
PY  - 2003
SN  - 1357-2725
ER  - 

TY  - JOUR
AU  - Serfling, E.*
AU  - Berberich-Siebelt, F.*
AU  - Avots, A.*
AU  - Chuvpilo, S.*
AU  - Klein-Hessling, S.*
AU  - Jha, M.K.*
AU  - Kondo, E.*
AU  - Pagel, P.
AU  - Schulze-Luehrmann, J.*
AU  - Palmetshofer, A.*
C1  - 9643
C2  - 21567
SP  - 1166-1170
TI  - NFAT and NF-kB factors - the distant relatives. 
JO  - Int. J. Biochem. Cell Biol.
VL  - 36
PY  - 2003
SN  - 1357-2725
ER  -