Christopher Horst Lillig

Christopher Horst Lillig
Universitätsmedizin Greifswald · Institute of Medical Biochemistry and Molecular Biology

PD Dr. rer. nat. Dr. rer. med. habil.
lost in thought

About

131
Publications
21,055
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Introduction
Our main interest is to identify thiol redox switches of physiological relevance and how these are altered in different disease conditions including cancer, Diabetes mellitus, neurodegenrative disorders, neuronal development, and inflammation.
Additional affiliations
October 2011 - July 2020
Universitätsmedizin Greifswald
Position
  • Principle Investigator / docent
October 2006 - September 2011
Philipps University of Marburg
Position
  • Group Leader
September 2001 - December 2007
Karolinska Institutet
Position
  • Group Leader
Education
July 2019 - July 2019
University of Greifswald
Field of study
  • Medical Biochemistry and Molecular Biology
July 2010 - July 2010
Philipps University of Marburg
Field of study
  • Biochemistry and Cell Biology
October 2001
The Medical Nobel Institute for Biochemistry, Karolinska Institutet
Field of study
  • Postdoctoral training

Publications

Publications (131)
Article
Full-text available
Thioredoxins, glutaredoxins, and peroxiredoxins have been characterized as electron donors, guards of the intracellular redox state, and 'antioxidants'. Today, these redoxins are increasingly recognized for their specific role in redox signaling. Redoxin research is by no means 'old-fashioned'; on the contrary, the number of publications on the top...
Article
Full-text available
Vertebrate-specific glutaredoxin 2 (Grx2) is expressed in at least two isoforms, mitochondrial Grx2a and cytosolic Grx2c. We have previously shown that cytosolic Grx2 is essential for embryonic development of the brain. In particular, we identified collapsin response mediator protein 2 (CRMP2/ DPYSL2), a mediator of the semaphorin-plexin signaling...
Article
Full-text available
Thiol-disulfide oxidoreductases from the thioredoxin (Trx) family of proteins have a broad range of well documented functions and possess distinct substrate specificities. The mechanisms and characteristics that control these specificities are key to the understanding of both the reduction of catalytic disulfides as well as allosteric disulfides (t...
Article
Glutaredoxins utilize the reducing power of glutathione to maintain and regulate the cellular redox state and redox-dependent signaling pathways, for instance, by catalyzing reversible protein S-glutathionylation. Due to the general importance of these processes, glutaredoxins have been implied in various physiological and disease-related condition...
Article
Full-text available
Despite their very close structural similarity, CxxC/S-type (class I) glutaredoxins (Grxs) act as oxidoreductases, while CGFS-type (class II) Grxs act as FeS cluster transferases. Here we show that the key determinant of Grx function is a distinct loop structure adjacent to the active site. Engineering of a CxxC/S-type Grx with a CGFS-type loop swi...
Article
Full-text available
Nucleoredoxin (Nrx) belongs to the Thioredoxin protein family and functions in redox-mediated signal transduction. It contains the dithiol active site motif Cys-Pro-Pro-Cys and interacts and regulates different proteins in distinct cellular pathways. Nrx was shown to be catalytically active in the insulin assay and recent findings indicate that Nrx...
Article
Full-text available
Thioredoxin (Trx) family proteins are key players in redox signaling. Here, we have analyzed glutaredoxin (Grx) 1 and Grx2 in age-related macular degeneration (AMD) and in retinal pigment epithelial (ARPE-19) cells. We hypothesized that these redoxins regulate cellular functions and signaling circuits such as cell proliferation, Wnt signaling and V...
Article
Full-text available
Purpose Thioredoxins are major regulatory proteins of oxidative signaling. Trx1 is the most prominent thioredoxin and, therefore, the current study sought to evaluate the prognostic role of Trx1 in ccRCC. Methods and patients A tissue micro-array (TMA) study was carried out to evaluate the association of Trx1 with clinicopathological features and...
Article
Full-text available
Purpose Although p53 is rarely mutated in ccRCC, its overexpression has been linked to poor prognosis. The current study sought to elucidate the unique role of p53 in ccRCC with genomic, proteomic, and functional analyses. Materials and methods Data from the Cancer Genome Atlas (TCGA) were evaluated for genomic and proteomic characteristics of p53...
Preprint
Full-text available
CRMP2/DPYL2 is an effector protein in the semaphorin signaling pathway that controls cytoskeletal dynamics, linking extracellular signals to the formation of axonal networks. CRMP2 is regulated by post-translational modifications including a dithiol-disulfide redox switch. The mechanisms of reduction of this switch were established, the signal-indu...
Article
Full-text available
The mammalian cytosolic thioredoxin (Trx) system consists of Trx1 and its reductase, the NADPH-dependent seleno-enzyme TrxR1. These proteins function as electron donor for metabolic enzymes, for instance in DNA synthesis, and the redox regulation of numerous processes. In this work, we analysed the interactions between these two proteins. We propos...
Preprint
Full-text available
Purpose Although p53 is rarely mutated in ccRCC, its overexpression has been linked to poor prognosis. The current study sought to elucidate the unique role of p53 in ccRCC with genomic, proteomic, and functional analyses. Materials and Methods Data from the Cancer Genome Atlas (TCGA) were evaluated for genomic and proteomic characteristics of p53...
Article
Full-text available
Ischemia and reperfusion events, such as myocardial infarction (MI), are reported to induce remote organ damage severely compromising patient outcomes. Tissue survival and functional restoration relies on the activation of endogenous redox regulatory systems such as the oxidoreductases of the thioredoxin (Trx) family. Trxs and peroxiredoxins (Prxs)...
Article
Full-text available
Environmental sequence data of microbial communities now makes up the majority of public genomic information. The assignment of a function to sequences from these metagenomic sources is challenging, because organisms associated with the data are often uncharacterized and not cultivable. To overcome these challenges, we created a rationally designed...
Article
Full-text available
Endogenous redox systems not only counteract oxidative damage induced by high levels of hydroxyl radicals (OH·) under pathological conditions, but also shape redox signaling as a key player in the regulation of physiological processes. Second messengers like hydrogen peroxide and nitric oxide, as well as redox enzymes of the Thioredoxin (Trx) famil...
Article
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Glutathione (GSH) was initially identified and characterized for its redox properties and later for its contributions to detoxification reactions. Over the past decade, however, the essential contributions of glutathione to cellular iron metabolism have come more and more into focus. GSH is indispensable in mitochondrial iron-sulfur (FeS) cluster b...
Preprint
Full-text available
Thioredoxins (Trxs) provide electrons to essential cellular processes such as DNA synthesis. Here, we characterize human and murine Trx1 as new iron-sulfur proteins. The [2Fe-2S] cluster is complexed using cysteinyl side chains 32 and 73 in a dimeric holocomplex. Formation of the holo-dimer depends on small structural changes of the loop connecting...
Article
The Front Cover shows pentathiepins racing to block the enzyme glutathione peroxidase 1 (GPx1), a key defense of tumor cells to cytotoxic hydrogen peroxide, which forms during chemotherapy. In an allegorical depiction, the tumor planet Oncos is under attack from hydrogen peroxide bombs, but these are quickly reduced to harmless water by the defendi...
Article
Full-text available
The failure of insulin-producing β-cells is the underlying cause of hyperglycemia in diabetes mellitus. β-cell decay has been linked to hypoxia, chronic inflammation, and oxidative stress. Thioredoxin (Trx) proteins are major actors in redox signaling and essential for signal transduction and the cellular stress response. We have analyzed the cytos...
Article
Full-text available
A novel class of glutathione peroxidase 1 (GPx1) inhibitors, namely tri‐ and tetracyclic‐ pentathiepins, has been identified that is ca. 15 times more potent than the most active known GPx1 inhibitor, mercaptosuccinic acid. Enzyme kinetic studies with bovine erythrocyte GPx1 indicate that pentathiepins reversibly inhibit oxidation of the substrate...
Article
Processing of and responding to various signals is an essential cellular function that influences survival, homeostasis, development, and cell death. Extra- or intracellular signals are perceived via specific receptors and transduced in a particular signalling pathway that results in a precise response. Reversible post-translational redox modificat...
Article
Backround Cytosolic glutaredoxin 2 (Grx2c) controls axonal outgrowth and is specifically induced in many cancer cell lines. We thus hypothesized that Grx2c promotes cell motility and invasiveness. Methods We characterized the impact of Grx2c expression in cell culture models. We combined stable isotope labeling, phosphopeptide enrichment, and high...
Article
Thioredoxin Family of proteins as Thioredoxin (Trxs), Glutaredoxins (Grxs) and Peroxiredoxins (Prxs) are one of the most important agents in the defense of oxidative stress and redox regulation. Perinatal asphyxia (AP) a disorder generated at the expense of the deficit of oxygen associated or not to ischemia, affects 5 to 10 of every 1,000 live bir...
Article
Thioredoxin family proteins are key modulators of cellular redox regulation and have been linked to several physiological functions, including the cellular response to hypoxia-ischemia. During perinatal hypoxia-ischemia (PHI), the central nervous system is subjected to a fast decrease in O2 and nutrients with a subsequent reoxygenation that ultimat...
Article
Seeds preserve a far developed plant embryo in a quiescent state. Seed metabolism relies on stored resources and is reactivated to drive germination when the external conditions are favorable. Since the switchover from quiescence to reactivation provides a remarkable case of a cell physiological transition we investigated the earliest events in ene...
Article
Full-text available
The spatio-temporal reduction and oxidation of protein thiols is an essential mechanism in signal transduction in all kingdoms of life. Thioredoxin (Trx) family proteins efficiently catalyze thiol-disulfide exchange reactions and the proteins are widely recognized for their importance in the operation of thiol switches. Trx family proteins have a b...
Preprint
Full-text available
Seeds preserve a far developed plant embryo in a quiescent state. Seed metabolism relies on stored resources and is re-activated to drive germination when the external conditions are favorable. Since the switchover from quiescence to re-activation provides a remarkable case of a cell physiological transition we investigated the earliest events in e...
Article
Full-text available
Nucleoredoxin (Nrx) is an oxidoreductase of the thioredoxin family of proteins. It was shown to act as a signal transducer in some pathways; however, so far, no comprehensive analysis of its regulated substrates and functions was available. Here, we used a combination of two different strategies to fill this gap. First, we analyzed the thiol-redox...
Article
Ischemic diseases, among others, myocardial infarction (MI), are the leading causes of death worldwide. MI is associated with a high tissue damage due in part to the activation of the immune response and the generation of reactive oxygen species (ROS), both taking place mainly during the reperfusion phase, once the blood supply to the tissue is res...
Article
Here we present the preparation of 14 pairs of cis- and trans-diammine monochlorido platinum(II) complexes, coordinated to heterocycles (i.e., imidazole, 2-methylimidazole and pyrazole) and linked to various acylhydrazones, which were designed as potential inhibitors of the selenium-dependent enzymes glutathione peroxidase 1 (GPx-1) and thioredoxin...
Article
Orthobunyaviruses are enveloped viruses that can cause human and animal diseases. A novel and major member is the Schmallenberg virus (SBV), the etiological agent of an emerging disease of ruminants that has been spreading all over Europe since 2011. The glycoproteins Gn and Gc of orthobunyaviruses mediate the viral entry, and specifically Gc is a...
Article
Full-text available
The general disruption of redox signaling following an ischemia-reperfusion episode has been proposed as a crucial component in neuronal death and consequently brain damage. Thioredoxin (Trx) family proteins control redox reactions and ensure protein regulation via specific, oxidative posttranslational modifications as part of cellular signaling pr...
Article
Demyelinated brain lesions, a hallmark of autoimmune neuroinflammatory diseases like multiple sclerosis, result from oligodendroglial cell damage. Activated microglia are considered a major source of nitric oxide and subsequent peroxynitrite-mediated damage of myelin. Here, we provide biochemical and biophysical evidence that the oxidoreductase glu...
Article
Full-text available
Significance: Glutathione is the most abundant cellular low molecular weight thiol in the majority of organisms in all kingdoms of life. Therefore, functions of glutathione and disturbed regulation of its concentration are associated with numerous physiological and pathological situations. Recent advances: The function of glutathione as redox buff...
Article
Full-text available
Collapsin response mediator protein CRMP2 (gene: DPYSL2) is crucial for neuronal development. The homotetrameric CRMP2 complex is regulated via two mechanisms, first by phosphorylation at, and second by reduction and oxidation of the Cys504 residues of two adjacent subunits. Here, we analyzed the effects of this redox switch on the protein in vitro...
Poster
Full-text available
Further simulations and their analysis open the possibility for future ligand interaction experiments.
Poster
Full-text available
presenting the extended structure of CRMP2 in oxidised and reduced form and comparing the first simulations with in vitro experiments.
Article
Peripheral nerve injury causes redox stress in injured neurons by upregulations of pro-oxidative enzymes, but most neurons survive suggesting an activation of endogenous defense against the imbalance. As potential candidates we assessed thioredoxin-fold proteins, called redoxins, which maintain redox homeostasis by reduction of hydrogen peroxide or...
Article
Full-text available
One of the promising possibilities of the clinical application of cold plasma, so-called cold atmospheric plasma (CAP), is its application on malignant cells and cancer tissue using its anti-neoplastic effects, primarily through the delivery of reactive oxygen and nitrogen species (ROS, RNS). In this study, we investigated the impact of CAP on cell...
Article
Objective: This study was carried out in order to examine the impact of long-term consumption of caramel-containing soft drinks (cola beverages) on glycemic balance and endocrine pancreas function and morphology in rats. Design and method: Sixty-four Wistar rats drank water (W), regular cola beverage (C, sucrose sweetened) for 6 months (treatment)....
Article
Full-text available
Protein cysteines can form transient disulfides with glutathione (GSH), resulting in the production of glutathionylated proteins, and this process is regarded as a mechanism by which the redox state of the cell can regulate protein function. Most studies on redox regulation of immunity have focused on intracellular proteins. In this study we have u...
Article
Full-text available
We report the effects of long-term cola beverage drinking on glucose homeostasis, endocrine pancreas function and morphology in rats. Wistar rats drank: water (group W), regular cola beverage (group C, sucrose sweetened) or "light" cola beverage (group L, artificially sweetened). After 6 months, 50% of the animals in each group were euthanized and...
Article
Full-text available
Non-classical protein secretion is of major importance as a number of cytokines and inflammatory mediators are secreted via this route. Current evidence indicates that there are several mechanistically distinct methods of non-classical secretion. We have recently shown that peroxiredoxin (Prdx) 1 and Prdx2 are released by various cells upon exposur...
Article
Full-text available
Abstract The spatiotemporal modification of specific cysteinyl residues in proteins has emerged as a novel concept in signal transduction. Such modifications alter the redox state of the cysteinyl thiol group with implications for the structure and biological function of the protein. Regulatory cysteines are therefore classified as 'thiol switches'...
Chapter
The cell signaling theory was developed from the analysis of signal transduction from extracellular signals to intracellular effector molecules via G-protein coupled receptors by Rodbell [1] and Gilman [2]. First, an extracellular signal activates a receptor protein or protein complex. Then, this activation promotes the release of second messenger...