Mariana M. Belcheva's research while affiliated with Washington University in St. Louis and other places

... One of the canonical signaling pathways of APJ receptor is G i -dependent phosphorylation of ERK1/2 that regulates the cell cycle and metabolism in the cell [32][33][34]. Several studies have demonstrated that the early phase of ERK1/2 phosphorylation of GPCRs is driven by G i protein in a protein kinase C-dependent pathway [35][36][37][38][39]. This early phase of ...

... Meperidine's κ-receptor binding may also contribute to its antineoplastic efficacy as opioids reduce cell proliferation in T47D breast cancer cells which mainly express κ-opioid receptors [7]. Despite MOR expression in glioblastoma cells [8][9][10], there exist few studies on the effects of opioids on these malignancies. Given meperidine's ability to readily cross the blood brain barrier, we will provide a broad review to explore its potential role in the management of glioblastoma, the most grave malignancy of the central nervous system. ...

... Opioids have been shown to impact astrocyte biology by modulating the expression and secretion of several of the previously mentioned synaptogenic factors [21,22] and other gliotransmitters [23], as well as exerting a strong influence on the differentiation and maturation of these cells [24], though rarely in the context of prenatal exposure. In this study, we investigated the impact of prenatal exposure to the opioid buprenorphine on the excitatory synaptogenic signaling and morphological development of astrocytes during a key time period for these processes, with potential implications for long-term synaptic connectivity and function in the POE brain. ...

... Conversely, propofol does not have these effects (34). In addition, opioids, widely used during anesthesia and perioperative period, were also proved to reduce activation of the pro-inflammatory transcription factor NF-kB, which was also detected by the Keywords burst detection in this study, and affect the adaptive immune system (33,35). Recent studies showed that morphine promotes the migration of MCF-7 cells via the TLR4/NF-kB signaling pathway (36). ...

... TSPs (particularly TSP-1 and 2 in developing mammalian brains) exert their synaptogenic effects by binding to α 2δ-1, a subunit of L-type voltage gated Ca +2 channels, on the surface of neurons at the site of synaptic terminals [13,22,23]. Opioid treatment in rodents has been shown not only to decrease astrocyte expression of TSPs [24,25], but also to interfere with normal astrocyte growth and development [26], indicating that astrocyte-induced synaptogenesis may be key to understanding the effects of opioids on neurological development. ...

... Another implication of these findings is that CaM may represent an alternative second messenger that could modulate MOR signaling via G proteins. We have studied the signaling roles for CaM at MOR in two pathways: one involving the phosphorylation of nuclear CREB (Wang et al., 2000a), and the other transactivation of EGFR (Belcheva et al., 2001). In either case, the use of MOR mutants unable to bind CaM but normal in G protein coupling (except for higher basal activity) showed significantly lower ability to stimulate these pathways. ...

... Among astrocyte cultures and some transfected cell lines, activation of ERK has been found by stimulating MOPR and KOPR. 38 MOPR and KOPR can induce ERK activation within 5À10 minutes. In case of MOPR mediation, ERK activation requires protein kinase C (PKCε) activity, while GRK-3 and arrestin are required for this activity in MOPR-dependent condition. ...

... Indeed, it has long-been suggested that opioids modify CNS plasticity or disease through actions in astroglia (Ronnback and Hansson 1988;Stiene-Martin and Hauser 1990;Deleo et al. 2004;Hauser et al. 2005;Narita et al. 2006;Hansson 2006;Kim et al. 2006;Hauser et al. 2007;Hutchinson et al. 2011). However, it has been quite difficult to separate, especially in vivo, the actions of opioids on glia from their effects on neurons, since all neural cell types examined thus far can express functional opioid receptors including MOR Eriksson et al. 1991;Bem et al. 1991;Barg et al. 1992;Hauser et al. 1996;Stiene-Martin et al. 1998;Knapp et al. 1998;Miyatake et al. 2009). These cell types include neurons, astroglia, microglia, oligodendroglia, and glial progenitors (Hauser et al. 2009;Hahn et al. 2010), as well as support cells within the CNS such as endothelial cells and the connective tissue stroma surrounding large blood Fig. 5 Time-dependent effects of exposure to morphine (Morph), X4/ R5-tropic HIV-1 gp120 MN and/or naloxone (Nal) in neuron and mixed-glial co-cultures for 72 h (a). ...

... KOP-mediated effects include inhibition of cAMP synthesis (Sharma et al., 1977) and calcium channels (Hescheler et al., 1987;Surprenant et al., 1990;Rusin et al., 1997), activation of potassium channels (North et al., 1987) and increased intracellular Ca 2+ levels (Jin et al., 1992). Protein kinase C and the inositol phosphatase are involved in the modulation of DNA synthesis by KOP agonists in fetal rat brain (Barg et al., 1993). Functionally significant is the activation of the MAP kinase pathways (Burt et al., 1996;Fukuda et al., 1996;Bruchas et al., 2006). ...

... The peptide AAVF (sequence FVVGQSY) is a short peptide from the adeno-associated virus protein coat, which was found through phage display studies and has recently been shown to have potential BBB targeting effects [43][44][45][46]. While this is already a huge bonus for the delivery of pharmaceutics across the BBB, these ligands have been demonstrated to have the potential for GBM specificity as well, but more thorough evaluations are required [47][48][49][50]. The two antibodies, M08J and M08, are two commercially available isoforms of Cell Surface Vimentin (CSV) antibodies that have different activities due to non-disclosed proprietary reasons [51]. ...