Brockmann A.,Universitatsstr 10 |
Strittmatter T.,Universitatsstr 10 |
May S.,Universitatsstr 10 |
Stemmer K.,Helmholtz Center Munich |
And 4 more authors.
ACS Chemical Biology | Year: 2014
Thiazolides are a novel class of anti-infectious agents against intestinal intracellular and extracellular protozoan parasites, bacteria, and viruses. While the parent compound nitazoxanide (NTZ; 2-(acetolyloxy)-N-(5-nitro-2- thiazolyl)benzamide) has potent antimicrobial activity, the bromo-thiazolide RM4819 (N-(5-bromothiazol-2-yl)-2-hydroxy-3-methylbenzamide) shows only reduced activity. Interestingly, both molecules are able to induce cell death in colon carcinoma cell lines, indicating that the molecular target in intestinal pathogens and in colon cancer cells is different. The detoxification enzyme glutathione S-transferase of class Pi 1 (GSTP1) is frequently overexpressed in various tumors, including colon carcinomas, and limits the efficacy of antitumor chemotherapeutic drugs due to its detoxifying activities. In colorectal tumor cells RM4819 has been shown to interact with GSTP1, and GSTP1 enzymatic activity is required for thiazolide-induced apoptosis. At present it is unclear which molecular structures of RM4819 are required to interact with GSTP1 and to induce cell death in colon carcinoma cell lines. Here, we demonstrate that novel thiazolide derivatives with variation in their substituents of the benzene ring do not significantly affect apoptosis induction in Caco-2 cells, whereas removal of the bromide atom on the thiazole ring leads to a strong reduction of cell death induction in colon cancer cells. We further show that active thiazolides require caspase activation and GSTP1 expression in order to induce apoptosis. We demonstrate that increased glutathione (GSH) levels sensitize colon cancer cells to thiazolides, indicating that both GSTP1 enzymatic activity as well as GSH levels are critical factors in thiazolide-induced cell death. © 2014 American Chemical Society.
Abedi-Lartey M.,Max Planck Institute for Ornithology (Radolfzell) |
Abedi-Lartey M.,University of Konstanz |
Abedi-Lartey M.,Universitatsstr 10 |
Dechmann D.K.N.,Max Planck Institute for Ornithology (Radolfzell) |
And 9 more authors.
Global Ecology and Conservation | Year: 2016
On-going fragmentation of tropical forest ecosystems and associated depletion of seed dispersers threatens the long-term survival of animal-dispersed plants. These threats do not only affect biodiversity and species abundance, but ultimately ecosystem functions and services. Thus, seed dispersers such as the straw-coloured fruit bat, E. helvum, which traverse long distances across fragmented landscapes, are particularly important for maintaining genetic connectivity and colonizing new sites for plant species. Using high-resolution GPS-tracking of movements, field observations and gut retention experiments, we quantify dispersal distances for small- and large-seeded fruits foraged by E. helvum during periods of colony population low (wet season) and high (dry season) in an urban and a rural landscape in the forest zone of Ghana. Gut passage time averaged 116 min (range 4-1143 min), comparable to other fruit bats. Movements were generally longer in the urban than in the rural landscape and also longer in the dry than in the wet season. As the majority of seeds are dispersed only to feeding roosts, median dispersal distances were similar for both large (42-67 m) and small (42-65 m) seeds. However, small seeds were potentially dispersed up to 75.4 km, four times further than the previous maximum distance estimated for a similar-sized frugivore. Maximum seed dispersal distances for small seeds were almost twice as long in the rural (49.7 km) compare to the urban (31.2 km) landscape. Within the urban landscape, estimated maximum dispersal distances for small seeds were three times longer during the dry season (75.4 km) compared to the wet season (22.8 km); in contrast, distances in the rural landscape were three times longer in the wet season (67 km) compared to the dry season (24.4). Dispersal distances for large seeds during the dry season (551 m) in the rural landscape were almost twice that in the wet season (319 m). We found no influence of food phenology on dispersal distances. The maximum likelihood for seed dispersal beyond feeding roosts (mean distance from food tree 263 m) was 4.7%. Small seeds were dispersed over even longer distances, >500 and >1000 m, with a likelihood of 3.0 % and 2.3 % respectively. Our data show that E. helvum retains ingested seeds for very long periods and may traverse large distances, probably making it an important long distance seed disperser in tropical Africa. We suggest E. helvumis important for ecosystem functioning and urge its conservation. © 2016 The Authors.