Activation of intracellular angiotensin AT 2 receptors induces rapid cell death in human uterine leiomyosarcoma cells

Abstract The presence of angiotensin type 2 (AT 2 ) receptors in mitochondria and their role in NO generation and cell aging were recently demonstrated in various human and mouse non-tumour cells. We investigated the intracellular distribution of AT 2 receptors including their presence in mitochondria and their role in the induction of apoptosis and cell death in cultured human uterine leiomyosarcoma (SK-UT-1) cells and control human uterine smooth muscle cells (HutSMC). The intracellular levels of the AT 2 receptor are low in proliferating SK-UT-1 cells but the receptor is substantially up-regulated in quiescent SK-UT-1 cells with high densities in mitochondria. Activation of the cell membrane AT 2 receptors by a concomitant treatment with angiotensin II and the AT 1 receptor antagonist, losartan, induces apoptosis but does not affect the rate of cell death. We demonstrate for the first time that the high-affinity, non-peptide AT 2 receptor agonist, Compound 21 (C21), penetrates the cell membrane of quiescent SK-UT-1 cells, activates intracellular AT 2 receptors and induces rapid cell death; approximately 70 % of cells died within 24 h. The cells, which escaped cell death, displayed activation of the mitochondrial apoptotic pathway, i.e. down-regulation of the Bcl-2 protein, induction of the Bax protein and activation of caspase-3. All quiescent SK-UT-1 cells died within 5 days after treatment with a single dose of C21. C21 was devoid of cytotoxic effects in proliferating SK-UT-1 cells and in quiescent HutSMC. Our results point to a new, unique approach enabling the elimination non-cycling uterine leiomyosarcoma cells providing that they over-express the AT 2 receptor

Activation of intracellular angiotensin AT2 receptors induces rapid cell death in human uterine leiomyosarcoma cells

Abstract The presence of angiotensin type 2 (AT 2 ) receptors in mitochondria and their role in NO generation and cell aging were recently demonstrated in various human and mouse non-tumour cells. We investigated the intracellular distribution of AT 2 receptors including their presence in mitochondria and their role in the induction of apoptosis and cell death in cultured human uterine leiomyosarcoma (SK-UT-1) cells and control human uterine smooth muscle cells (HutSMC). The intracellular levels of the AT 2 receptor are low in proliferating SK-UT-1 cells but the receptor is substantially up-regulated in quiescent SK-UT-1 cells with high densities in mitochondria. Activation of the cell membrane AT 2 receptors by a concomitant treatment with angiotensin II and the AT 1 receptor antagonist, losartan, induces apoptosis but does not affect the rate of cell death. We demonstrate for the first time that the high-affinity, non-peptide AT 2 receptor agonist, Compound 21 (C21), penetrates the cell membrane of quiescent SK-UT-1 cells, activates intracellular AT 2 receptors and induces rapid cell death; approximately 70 % of cells died within 24 h. The cells, which escaped cell death, displayed activation of the mitochondrial apoptotic pathway, i.e. down-regulation of the Bcl-2 protein, induction of the Bax protein and activation of caspase-3. All quiescent SK-UT-1 cells died within 5 days after treatment with a single dose of C21. C21 was devoid of cytotoxic effects in proliferating SK-UT-1 cells and in quiescent HutSMC. Our results point to a new, unique approach enabling the elimination non-cycling uterine leiomyosarcoma cells providing that they over-express the AT 2 receptor

Rehderodendron truongsonense (Styracaceae), a new species from Vietnam

Rehderodendron truongsonense, a new species from Vietnam, is described and illustrated. In the treatment of the Styracaceae for the Flore du Cambodge, du Laos, et du Viêtnam, specimens of this species were recognized as R. macrocarpum Hu. These specimens clearly differ from R. macrocarpum, however, as well as from all other species of Rehderodendron (where these characters are known) by, e.g., an evergreen ver- sus deciduous habit, fewer secondary veins of the leaf blade, shorter inflorescences and corolla lobes, large and conspicuous lowermost bracteoles, the presence of eight ovules per carpel, and a fruit with ca. 10 to 20 ribs that are indistinct. Phylogenetic analysis based on five chloroplast DNA regions (clpP-psbB, ndhD-psaC-ndhE-ndhG, rpl22-rps19, rps18-rpl20, and psbI-trnS-GCU) placed the new species as nested within Rehderodendron and sister to R. gongshanense. This new species is endemic to the Truong Son Mountain Range, from which the epi- thet is derived, and we assign it an IUCN Red List preliminary status as Near Threatened.

Symbiotic Interplay of Fungi, Algae, and Bacteria within the Lung Lichen <i>Lobaria pulmonaria</i> L. Hoffm. as Assessed by State-of-the-Art Metaproteomics

Lichens are recognized by macroscopic structures formed by a heterotrophic fungus, the mycobiont, which hosts internal autotrophic photosynthetic algal and/or cyanobacterial partners, referred to as the photobiont. We analyzed the structure and functionality of the entire lung lichen <i>Lobaria pulmonaria</i> L. Hoffm. collected from two different sites by state-of-the-art metaproteomics. In addition to the green algae and the ascomycetous fungus, a lichenicolous fungus as well as a complex prokaryotic community (different from the cyanobacteria) was found, the latter dominated by methanotrophic <i>Rhizobiales</i>. Various partner-specific proteins could be assigned to the different lichen symbionts, for example, fungal proteins involved in vesicle transport, algal proteins functioning in photosynthesis, cyanobacterial nitrogenase and GOGAT involved in nitrogen fixation, and bacterial enzymes responsible for methanol/C1-compound metabolism as well as CO-detoxification. Structural and functional information on proteins expressed by the lichen community complemented and extended our recent symbiosis model depicting the functional multiplayer network of single holobiont partners. Our new metaproteome analysis strongly supports the hypothesis (i) that interactions within the self-supporting association are multifaceted and (ii) that the strategy of functional diversification within the single lichen partners may support the longevity of <i>L. pulmonaria</i> under certain ecological conditions

Symbiotic Interplay of Fungi, Algae, and Bacteria within the Lung Lichen <i>Lobaria pulmonaria</i> L. Hoffm. as Assessed by State-of-the-Art Metaproteomics

Lichens are recognized by macroscopic structures formed by a heterotrophic fungus, the mycobiont, which hosts internal autotrophic photosynthetic algal and/or cyanobacterial partners, referred to as the photobiont. We analyzed the structure and functionality of the entire lung lichen <i>Lobaria pulmonaria</i> L. Hoffm. collected from two different sites by state-of-the-art metaproteomics. In addition to the green algae and the ascomycetous fungus, a lichenicolous fungus as well as a complex prokaryotic community (different from the cyanobacteria) was found, the latter dominated by methanotrophic <i>Rhizobiales</i>. Various partner-specific proteins could be assigned to the different lichen symbionts, for example, fungal proteins involved in vesicle transport, algal proteins functioning in photosynthesis, cyanobacterial nitrogenase and GOGAT involved in nitrogen fixation, and bacterial enzymes responsible for methanol/C1-compound metabolism as well as CO-detoxification. Structural and functional information on proteins expressed by the lichen community complemented and extended our recent symbiosis model depicting the functional multiplayer network of single holobiont partners. Our new metaproteome analysis strongly supports the hypothesis (i) that interactions within the self-supporting association are multifaceted and (ii) that the strategy of functional diversification within the single lichen partners may support the longevity of <i>L. pulmonaria</i> under certain ecological conditions