Heat Shock Inhibition of CDK5 Increases NOXA Levels through miR-23a Repression

Hyperthermia is a proteotoxic stress that is lethal when exposure is extreme but also cytoprotective in that sublethal exposure leads to the synthesis of heat shock proteins, including HSP70, which are able to inhibit stress-induced apoptosis. CDK5 is an atypical cyclin-dependent kinase family member that regulates many cellular functions including motility and survival. Here we show that exposure of a human lymphoid cell line to hyperthermia causes CDK5 insolubilization and loss of tyrosine-15 phosphorylation, both of which were prevented in cells overexpressing HSP70. Inhibition of CDK5 activity with roscovitine-sensitized cells to heat induced apoptosis indicating a protective role for CDK5 in inhibiting heat-induced apoptosis. Both roscovitine and heat shock treatment caused increased accumulation of NOXA a pro-apoptotic BH3-only member of the BCL2 family. The increased abundance of NOXA by CDK5 inhibition was not a result of changes in NOXA protein turnover. Instead, CDK5 inhibition increased NOXA mRNA and protein levels by decreasing the expression of miR-23a, whereas overexpressing the CDK5 activator p35 attenuated both of these effects on NOXA and miR-23a expression. Lastly, overexpression of miR-23a prevented apoptosis under conditions in which CDK5 activity was inhibited. These results demonstrate that CDK5 activity provides resistance to heat-induced apoptosis through the expression of miR-23a and subsequent suppression of NOXA synthesis. Additionally, they indicate that hyperthermia induces apoptosis through the insolubilization and inhibition of CDK5 activity.     

Die Oarex-Arten der Innsbrucker Flora

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Wichtigere neue Funde von Phanerogamen in Nordtirol

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Weitere Beiträge zur Kenntnis der Eu-Hieracien Tirols,Südbayerns und der österreichischen Alpenländer

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Die Piloselloiden Oberösterreichs

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Ein Beitrag zur Flora von Nordtirol

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Experimentelle Abkürzung der Tragdauer durch Wärme

Ohne ZusammenfassungEin Auszug dieser Arbeit erschien unter dem Titel: Mitteilungen aus der Biologischen Versuchsanstalt usw. Nr. 179 im Akad. Anz. Wien, Nr 26, vom 10. Dez. 1931.     

Hypogonadotropic hypogonadism in men with hereditary hemochromatosis

Hereditary hemochromatosis is a genetic disease that progresses silently. This disease is often diagnosed late when complications appear. Hypogonadotropic hypogonadism (HH) is one of the classical complications of hemochromatosis. Its frequency is declining probably because of earlier diagnosis and better informed physicians. Certain symptoms linked to HH can have an impact on a patient’s sexuality, such as decreased libido, erectile dysfunction, and impairment of ejaculation, as well as on his reproductive capacities.This review is based on an online search in English, French and German language publications found in PubMed/Medline, up to 23 September 2016 using the following key word: Male infertility, Hypogonadotropic Hypogonadism, Hereditary Hemochromatosis.Thirty-four papers met these inclusion criteria. This review describes the impact of iron overload on male fertility, resulting in hypogonadotropic hypogonadism and proposes treatment modalities.     

A Unique Expression of Keratin 14 in a Subset of Trophoblast Cells

The placenta, a transient organ in human, is essential for pregnancy maintenance and for fetal growth and development. Trophoblast and stromal cells are the main cell types present in human placenta. Trophoblast cells are present in different subtypes depending on their differentiation state and their temporal and spatial location during pregnancy. The stromal cells are of extraembryonic mesenchymal origin and are important for villous formation and maintenance. Interestingly, many pregnancy–related diseases are associated with defect in trophoblast differentiation and villous integrity. Therefore, it''s crucial to specifically identify each type of placental cells using specific markers. Keratins (CK) are widely used as marker of epithelial cells, cancer origin identification and in some cases as marker of stem/progenitor cells. Vimentin is widely used as marker of mesenchymal cells. The aim of this study is to characterize the presence of different keratins in human trophoblast cells and vimentin in stromal cells. Using immunohistochemistry on term placental sections, our results show that vimentin is solely expressed in stromal-mesenchymal cells while keratins 5, 7, 8, 14 and 19 are expressed in trophoblast cells. Interestingly, all keratins tested, except for keratin 14, were evenly expressed in all trophoblast cells. Keratin 14 was expressed in a subset of CK7 positive cells. Moreover, the same results were obtained when using freshly isolated cytotrophoblast cells or BeWo cells. In conclusion, this study is a crucial step in the advancement of our knowledge in placental cell type identification and characterization.