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Dive into the research topics where Angelika Kümin is active.

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Featured researches published by Angelika Kümin.


Molecular and Cellular Biology | 2006

Nrf transcription factors in keratinocytes are essential for skin tumor prevention but not for wound healing.

Ulrich auf dem Keller; Marcel Huber; Tobias A. Beyer; Angelika Kümin; Christina Siemes; Susanne Braun; Philippe Bugnon; Varvara Mitropoulos; Delinda A. Johnson; Jeffrey A. Johnson; Daniel Hohl; Sabine Werner

ABSTRACT The Nrf2 transcription factor is a key player in the cellular stress response through its regulation of cytoprotective genes. In this study we determined the role of Nrf2-mediated gene expression in keratinocytes for skin development, wound repair, and skin carcinogenesis. To overcome compensation by the related Nrf1 and Nrf3 proteins, we expressed a dominant-negative Nrf2 mutant (dnNrf2) in the epidermis of transgenic mice. The functionality of the transgene product was verified in vivo using mice doubly transgenic for dnNrf2 and an Nrf2-responsive reporter gene. Surprisingly, no abnormalities of the epidermis were observed in dnNrf2-transgenic mice, and even full-thickness skin wounds healed normally. However, the onset, incidence, and multiplicity of chemically induced skin papillomas were strikingly enhanced, whereas the progression to squamous cell carcinomas was unaltered. We provide evidence that the enhanced tumorigenesis results from reduced basal expression of cytoprotective Nrf target genes, leading to accumulation of oxidative damage and reduced carcinogen detoxification. Our results reveal a crucial role of Nrf-mediated gene expression in keratinocytes in the prevention of skin tumors and suggest that activation of Nrf2 in keratinocytes is a promising strategy to prevent carcinogenesis of this highly exposed organ.


Journal of Cell Biology | 2007

Peroxiredoxin 6 is required for blood vessel integrity in wounded skin

Angelika Kümin; Matthias Schäfer; Nikolas Epp; Philippe Bugnon; Christiane Born-Berclaz; Annette Oxenius; Anke Klippel; Wilhelm Bloch; Sabine Werner

Peroxiredoxin 6 (Prdx6) is a cytoprotective enzyme with largely unknown in vivo functions. Here, we use Prdx6 knockout mice to determine its role in UV protection and wound healing. UV-mediated keratinocyte apoptosis is enhanced in Prdx6-deficient mice. Upon skin injury, we observe a severe hemorrhage in the granulation tissue of knockout animals, which correlates with the extent of oxidative stress. At the ultrastructural level endothelial cells appear highly damaged, and their rate of apoptosis is enhanced. Knock-down of Prdx6 in cultured endothelial cells also increases their susceptibility to oxidative stress, thus confirming the sensitivity of this cell type to loss of Prdx6. Wound healing studies in bone marrow chimeric mice demonstrate that Prdx6-deficient inflammatory and endothelial cells contribute to the hemorrhage phenotype. These results provide insight into the cross-talk between hematopoietic and resident cells at the wound site and the role of reactive oxygen species in this interplay.


European Journal of Cell Biology | 2004

Keratinocyte growth factor: effects on keratinocytes and mechanisms of action.

Ulrich auf dem Keller; Monika Krampert; Angelika Kümin; Susanne Braun; Sabine Werner

Keratinocyte growth factor (KGF) is a potent and specific mitogen for different types of epithelial cells, and it can protect these cells from various insults. Due to these properties, it is of particular importance for the repair of injured epithelial tissues, and it is currently therapeutically explored for the treatment of radiation- and chemotherapy-induced mucosal epithelial damage in cancer patients. In this review we summarize the current knowledge on the role of KGF in tissue repair and cytoprotection, and we report on its mechanisms of action in keratinocytes.


Journal of Cell Science | 2006

Keratinocyte growth factor protects epidermis and hair follicles from cell death induced by UV irradiation, chemotherapeutic or cytotoxic agents

Susanne Braun; Monika Krampert; Enikö Bodó; Angelika Kümin; Christiane Born-Berclaz; Ralf Paus; Sabine Werner

Owing to its potent cytoprotective properties for epithelial cells, keratinocyte growth factor (KGF) is successfully used for the treatment of chemotherapy- and radiotherapy-induced oral mucositis in cancer patients. It is therefore of major interest to determine possible clinical applications of KGF in other organs and in different stress situations and to unravel common and organ-specific mechanisms of KGF action. Here we show that KGF protects human keratinocytes from the toxicity of xenobiotics with electrophilic and oxidative properties and reduces the cell death induced by UV irradiation. In contrast to other cell types, cytoprotection of keratinocytes by KGF is not a direct anti-apoptotic effect but requires de novo protein synthesis. The in vitro findings are clinically relevant because KGF protected keratinocytes in organ-cultured human scalp hair follicles from the toxicity of the xenobiotic menadione. Moreover, injection of KGF into murine back skin markedly reduced cell death in the epidermis after UVB irradiation. This activity is dependent on FGF receptor signaling because it was abrogated in transgenic mice expressing a dominant-negative FGF receptor mutant in keratinocytes. Taken together, our results encourage the use of KGF for skin protection from chemical and physical insults.


Molecular and Cellular Biology | 2002

Basolateral Targeting of ERBB2 Is Dependent on a Novel Bipartite Juxtamembrane Sorting Signal but Independent of the C-Terminal ERBIN-Binding Domain

Christian Dillon; Anna Creer; Karen Kerr; Angelika Kümin; Clive Dickson

ABSTRACT ERBB2 is a receptor tyrosine kinase present on the basolateral membrane of polarized epithelia and has important functions in organ development and tumorigenesis. Using mutagenic analyses and Madin-Darby canine kidney (MDCK) cells, we have investigated the signals that regulate basolateral targeting of ERBB2. We show that basolateral delivery of ERBB2 is dependent on a novel bipartite juxtamembrane sorting signal residing between Gln-692 and Thr-701. The signal shows only limited sequence homology to known basolateral targeting signals and is both necessary and sufficient for correct sorting of ERBB2. In addition we demonstrate that this motif can function as a dominant basolateral targeting signal by its ability to redirect the apically localized P75 neurotrophin receptor to the basolateral membrane domain of polarized epithelial cells. Interestingly, LLC-PK1 cells, which are deficient for the μ1B subunit of the AP1B adaptor complex, missort a large proportion of ERBB2 to the apical membrane domain. This missorting can be partially corrected by the introduction of μ1B, suggesting a possible role for AP1B in ERBB2 endosomal trafficking. Furthermore, we find that the C-terminal ERBIN binding domain of ERBB2 is not necessary for its basolateral targeting in MDCK cells.


Free Radical Biology and Medicine | 2005

Heterozygous deficiency of manganese superoxide dismutase results in severe lipid peroxidation and spontaneous apoptosis in murine myocardium in vivo.

Maria Strassburger; Wilhelm Bloch; Silke Sulyok; Jutta Schüller; Alexander F. Keist; Annette Schmidt; Jutta Wenk; Thorsten Peters; Meinhard Wlaschek; Thomas Krieg; Martin Hafner; Angelika Kümin; Sabine Werner; Werner Müller; Karin Scharffetter-Kochanek


American Journal of Pathology | 2006

Peroxiredoxin 6 is a potent cytoprotective enzyme in the epidermis

Angelika Kümin; Christine Huber; Thomas Rülicke; Eckhard Wolf; Sabine Werner


Journal of Investigative Dermatology Symposium Proceedings | 2006

Reactive Oxygen Species and Their Detoxification in Healing Skin Wounds

Ulrich auf dem Keller; Angelika Kümin; Susanne Braun; Sabine Werner


Life Sciences | 2007

Isoform-specific downregulation of peroxiredoxin in human failing myocardium.

Klara Brixius; Robert H. G. Schwinger; Felix Hoyer; Andreas Napp; Robert Renner; Birgit Bölck; Angelika Kümin; Uwe Fischer; Uwe Mehlhorn; Sabine Werner; Wilhelm Bloch


Free Radical Biology and Medicine | 2006

Corrigendum to “Heterozygous deficiency of manganese superoxide dismutase results in severe lipid peroxidation and spontaneous apoptosis in murine myocardium in vivo” [Free Radic. Biol. Med. 38:1458–1470; 2005]

Maria Strassburger; Wilhelm Bloch; Silke Sulyok; Jutta Schüller; Alexander F. Keist; Annette Schmidt; Jutta Wenk; Thorsten Peters; Meinhard Wlaschek; Jacek Lenart; Thomas Krieg; Martin Hafner; Angelika Kümin; Sabine Werner; Werner Müller; Karin Scharffetter-Kochanek

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Wilhelm Bloch

German Sport University Cologne

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