A5061443441- Autophagy in Disease and Therapy
- Microbial Natural Products and Biosynthesis
- Calcium signaling and nucleotide metabolism
- Marine Sponges and Natural Products
- Adenosine and Purinergic Signaling
- Epigenetics and DNA Methylation
- Crystallization and Solubility Studies
- Cancer therapeutics and mechanisms
- X-ray Diffraction in Crystallography
- Synthetic Organic Chemistry Methods
- Histone Deacetylase Inhibitors Research
- Plant Pathogens and Fungal Diseases
- Mitochondrial Function and Pathology
- Essential Oils and Antimicrobial Activity
- Polyamine Metabolism and Applications
- ATP Synthase and ATPases Research
- Cell death mechanisms and regulation
- Vibrio bacteria research studies
- Glioma Diagnosis and Treatment
- Flavonoids in Medical Research
- Cellular transport and secretion
- Genomics, phytochemicals, and oxidative stress
- Ferroptosis and cancer prognosis
- Microtubule and mitosis dynamics
- Bioactive natural compounds
Heinrich Heine University Düsseldorf
2015-2022
Düsseldorf University Hospital
2019-2022
Institute of Molecular Medicine
2015-2022
Faculty (United Kingdom)
2017-2020
Hochschule Düsseldorf University of Applied Sciences
2017
Abstract Ferroptosis is a form of regulated cell death that emerges to be relevant for therapy-resistant and dedifferentiating cancers. Although several lines evidence suggest ferroptosis type autophagy-dependent death, the underlying molecular mechanisms remain unclear. Fin56, 3 inducer, triggers by promoting glutathione peroxidase 4 (GPX4) protein degradation via not fully understood pathway. Here, we determined Fin56 induces autophagy in bladder cancer cells Fin56-triggered...
Macroautophagy/autophagy and necroptosis represent two opposing cellular s tress responses. Whereas autophagy primarily fulfills a cyto-protective function, is form of regulated cell death induced via receptors. Here, we aimed at investigating the molecular crosstalk between these pathways. We observed that RIPK3 directly associates with AMPK phosphorylates its catalytic subunit PRKAA1/2 T183/T172. Activated then autophagy-regulating proteins ULK1 BECN1. However, lysosomal degradation...
Autophagy describes an intracellular process responsible for the lysosome-dependent degradation of cytosolic components. The ULK1/2 complex comprising kinase and accessory proteins ATG13, RB1CC1, ATG101 has been identified as a central player in autophagy network, it represents main entry point autophagy-regulating kinases such MTOR AMPK. It is generally accepted that ULK1 constitutively assembled independent nutrient supply. Here we report characterization ATG13 region required binding...
A new epidithiodiketopiperazine (ETP), pretrichodermamide G (1), along with three known (epi)dithiodiketopiparazines (2-4) were isolated from cultures of Trichoderma harzianum and Epicoccum nigrum, endophytic fungi associated medicinal plants Zingiber officinale Salix sp., respectively. The structure the compound (1) was established on basis spectroscopic data, including 1D/2D NMR HRESIMS. compounds investigated for their antifungal, antibacterial cytotoxic potential against a panel...
Autophagy, apoptosis, and necroptosis are stress responses governing the ultimate fate of a cell. However, crosstalk between these cellular is not entirely understood. Especially, it clear whether autophagy-initiating kinase ULK1 cell-death-regulating RIPK1 involved in this potential crosstalk. Here, we identify as substrate ULK1. ULK1-dependent phosphorylation reduces complex IIb/necrosome assembly tumor necrosis factor (TNF)-induced cell death, whereas deprivation enhances TNF-induced...
Macroautophagy/autophagy is an evolutionarily conserved cellular process whose induction regulated by the ULK1 protein kinase complex. The subunit ATG13 functions as adaptor recruiting ULK1, RB1CC1 and ATG101 to a core Furthermore, directly binds both phospholipids members of Atg8 family. central involvement in complex formation makes it attractive target for autophagy regulation. Here, we analyzed known interactions with proteins lipids their potential modulation induction. Targeting...
Cisplatin-based regimens are routinely employed for the treatment of urothelial carcinoma. However, therapeutic success is hampered by primary presence or development cisplatin resistance. This chemoresistance executed multiple cellular pathways. In recent years, process autophagy has been identified as a prosurvival pathway cancer cells. On one hand, enables cells to survive conditions low oxygen nutrient supply, frequently found in tumors. other supports Here, we aimed at investigating...
Abstract The protein kinase TBK1 is a central regulator of innate immune responses and autophagy, ablation either function has been linked to neuroinflammatory or degenerative diseases. Autophagy an intracellular process that recycles old damaged proteins organelles. In recent years, the TBK1-dependent regulation autophagy pathways characterized. However, autophagy-dependent activity awaits further clarification. Here, we observed recruited SQSTM1/p62-containing aggregates via selective...
Autophagy represents an intracellular degradation process which is involved in both regular cell homeostasis and disease settings. In recent years, the molecular machinery governing this has been elucidated. The ULK1 kinase complex consisting of serine/threonine protein adapter proteins ATG13, RB1CC1, ATG101, centrally regulation autophagy initiation. This turn regulated by activity different nutrient- or energy-sensing kinases, including MTOR, AMPK, AKT. However, next to phosphorylation...
Three new benzo[<italic>j</italic>]fluoranthene metabolites, including an isolation artefact which induces intrinsic apoptosis and blocks autophagy, were isolated from<italic>Annulohypoxylon</italic>sp.
Abstract Mitochondria are cellular organelles with crucial functions in the generation and distribution of ATP, buffering cytosolic Ca 2+ initiation apoptosis. Compounds that interfere these termed mitochondrial toxins, many which derived from microbes, such as antimycin A, oligomycin ionomycin. Here, we identify mycotoxin phomoxanthone A (PXA), endophytic fungus Phomopsis longicolla , a toxin. We show PXA elicits strong release mitochondria but not ER. In addition, depolarises similarly to...
Investigation of the sponge Clathria basilana collected in Indonesia afforded five new peptides, including microcionamides C (1) and D (2), gombamides B (4), (5), (6), an unusual amide, (E)-2-amino-3-methyl-N-styrylbutanamide (7), along with 11 known compounds, among them microcionamide A (3). The structures compounds were elucidated by one- two-dimensional NMR spectroscopy as well high-resolution mass spectrometry. absolute configurations constituent amino acid residues 1–7 determined...
Fermentation of the endophytic fungus
Didymellanosine (1), the first analogue of decahydrofluorene-class natural products bearing a 13-membered macrocyclic alkaloid conjugated with adenosine, and new benzolactone derivative, ascolactone C (4) along eight known compounds (2, 3, 5-10), were isolated from solid rice fermentation endophytic fungus Didymella sp. IEA-3B.1 derived host plant Terminalia catappa. In addition, ascochitamine (11) was obtained when (NH4)2SO4 added to medium is reported here for time as product. (1)...
Abstract Autophagy is an intracellular recycling pathway with implications for homeostasis and cell survival. Its pharmacological modulation can aid chemotherapy by sensitizing cancer cells toward approved drugs overcoming chemoresistance. Recent translational data on autophagy modulators show promising results in reducing tumor growth metastasis, but also reveal a need more specific compounds novel lead structures. Here, we searched such autophagy-modulating flow cytometry-based...
Abstract Inhibition of the mitochondrial metabolism offers a promising therapeutic approach for treatment cancer. Here, we identify mycotoxin viriditoxin (VDT), derived from endophytic fungus Cladosporium cladosporioides , as an interesting candidate leukemia and lymphoma treatment. VDT displayed high cytotoxic potential rapid kinetics caspase activation in Jurkat Ramos cells contrast to solid tumor that were affected much lesser extent. Most remarkably, human hematopoietic stem progenitor...
There is a variety of antineoplastic drugs that are based on natural compounds from ecological niches with high evolutionary pressure. We used two cell lines (Jurkat J16 and Ramos) in screening to assess 300 different naturally occurring regard their activity. The results the 4,6-dibromo-2-(2′,4′-dibromophenoxy)phenol (P01F03), 4,5,6-tribromo-2-(2′,4′-dibromophenoxy)phenol (P01F08), 5-epi-nakijinone Q (P03F03) prompted us perform further research. Using viability apoptosis assays primary...
Abstract Many proteins of the Repeats in Toxins (RTX) protein family are toxins Gram-negative pathogens including hemolysin A (HlyA) uropathogenic E. coli . RTX secreted via Type I secretion systems (T1SS) and adopt their native conformation Ca 2+ -rich extracellular environment. Here we employed HlyA T1SS as a heterologous surrogate system for toxin MbxA from bovine pathogen Moraxella bovis In successfully activates substrate by acylation secretes precursor proMbxA active allowing...