Anti-PDIA6 monoclonal antibody Made to order

The abuse of anabolic androgenic steroids (AAS) has been considered a major public health problem during decades. Supraphysiological doses of AAS may lead to a variety of neuroendocrine problems. Precisely, the hypothalamic-pituitary-gonadal (HPG) axis is one of the body systems that is mainly influenced by steroidal hormones. Fluctuations of the hormonal milieu result in alterations of reproductive function, which are made through changes in hypothalamic neurons expressing gonadotropin-releasing hormone (GnRH). In fact, previous studies have shown that AAS modulate the activity of these neurons through steroid-sensitive afferents. To increase knowledge about the cellular mechanisms induced by AAS in GnRH neurons, we performed proteomic analyses of the murine hypothalamic GT1-7 cell line after exposure to 17a-methyltestosterone (17 alpha-meT; 1 mu M). These cells represent a good model for studying regulatory processes because they exhibit the typical characteristics of GnRH neurons, and respond to compounds that modulate GnRH in vivo. Two-dimensional difference in gel electrophoresis (2D-DIGE) and mass spectrometry analyses identified a total of 17 different proteins that were significantly affected by supraphysiological levels of AAS. Furthermore, pathway analyses showed that modulated proteins were mainly associated to glucose metabolism, drug detoxification, stress response and cell cycle. Validation of many of these proteins, such as GSTM1, ERH, GAPDH, PEBP1 and PDIA6, were confirmed by western blotting. We further demonstrated that AAS exposure decreased expression of estrogen receptors and GnRH, while two important signaling pathway proteins p-ERK, and p-p38, were modulated. Our results suggest that steroids have the capacity to directly affect the neuroendocrine system by modulating key cellular processes for the control of reproductive function.

Stress-related immunity can be activated in the course of lymphoproliferative disorders, including Hodgkin's lymphoma, upon the interaction between killer cell lectin-like receptor subfamily K, member 1 (KLRK1, best known as NKG2D) on effector lymphocytes and NKG2D ligands (NKG2DL), such as MHC class I polypeptide-related sequence a (MICa), MICB and various UL16-binding proteins (ULBPs), on lymphoma cells. However, NKG2DLs can also bind NKG2D upon shedding, thus affecting the recognition of lymphoma cells by the immune system. The proteolytic cleavage of MICa depends on protein disulfide isomerase family a, member 6 (PDIA6, a thiol isomerase best known as ERp5) as well as on the disintegrins and metalloproteinases ADAM metallopeptidase domain 10 (ADAM10) and ADAM17, which also cleave ULPBs. These enzymes can be targeted in novel therapeutic schemes to avoid the escape of malignant cells from stress-evoked immune responses.