Differential Biological Effects of K252 Kinase Inhibitors Are Related to Membrane Solubility but Not to Permeability

Ross, Alonzo H.; McKinnon, Christine A.; Daou, Marie‐Claire; Ratliff, Kristin R.; Wolf, David E.

doi:10.1046/j.1471-4159.1995.65062748.x

Cited by 26 publications

(15 citation statements)

References 14 publications

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“…COCs were washed twice, transferred to modified M16 medium (Specialty Media) without FBS, and cultured with or without different doses of BDNF, mouse nerve growth factor (NGF; R & D Systems), or human neurotrophin-3 (NT-3) (R & D Systems) for 20 h at 37°C in 5% CO 2 ͞95% air. Some COCs were also cultured with BDNF with or without the TrkB ectodomain (R & D Systems), panspecific Trk receptor inhibitor K252a (Calbiochem) (10), or K252b (11). The occurrence of first polar body extrusion in the oocyte was examined after removing cumulus cells by using a small-bore pipette under Hoffman contrast microscopy (Nikon).…”

Section: Methodsmentioning

confidence: 99%

Ovarian brain-derived neurotrophic factor (BDNF) promotes the development of oocytes into preimplantation embryos

Kawamura

Mulders

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

168

126

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Optimal development of fertilized eggs into preimplantation embryos is essential for reproduction. Although mammalian oocytes ovulated after luteinizing hormone (LH) stimulation can be fertilized and promoted into early embryos in vitro, little is known about ovarian factors important for the conditioning of eggs for early embryo development. Because LH interacts only with ovarian somatic cells, its potential regulation of oocyte functions is presumably mediated by local paracrine factors. We performed DNA microarray analyses of ovarian transcripts and identified brainderived neurotrophic factor (BDNF) secreted by granulosa and cumulus cells as an ovarian factor stimulated by the preovulatory LH surge. Ovarian BDNF acts on TrkB receptors expressed exclusively in oocytes to enhance first polar body extrusion of oocytes and to promote the in vitro development of zygotes into preimplantation embryos. Furthermore, in vivo treatment with a Trk receptor inhibitor suppressed first polar body extrusion and the progression of zygotes into blastocysts. Thus, ovarian BDNF is important to nuclear and cytoplasmic maturation of the oocyte, which is essential for successful oocyte development into preimplantation embryos. Treatment with BDNF could condition the cultured oocytes for optimal progression into the totipotent blastocysts.early embryo development ͉ gonadotropins ͉ ovulation I n vertebrates, rupture of ovarian follicles and final maturation of oocytes occur in response to stimulation by pituitaryderived luteinizing hormones (LH) that act on the somatic granulosa and theca cells surrounding the oocyte. Shortly after stimulation by the preovulatory surge of LH, oocytes arrested at the late prophase resume meiosis characterized by germinal vesicle (nuclear envelope) breakdown (GVBD), chromosome condensation, and extrusion of the first polar body in preparation for fertilization and early embryonic development. Recent studies demonstrated that the endocrine hormone LH stimulates ovarian production of EGF-like factors from granulosa cells and insulin-like 3 from theca cells to promote GVBD (1, 2). In addition to nuclear maturation exemplified by GVBD and extrusion of the first polar body to complete the first meiotic division, oocytes also undergo cytoplasmic maturation characterized by cytoplasmic changes essential for monospermic fertilization, processing of the sperm, and preparation for development to preimplantation embryos (3, 4). Although the spermatozoon provides an essential element for embryo generation, the developmental fate of the embryo is principally dictated by the oocyte. However, few studies have explored ovarian factors that may be important for the conditioning of the oocyte in preparation for fertilization and preimplantation development.Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of proteins known to activate the highaffinity TrkB receptor and the pan-neurotrophin low-affinity receptor p75 (5). Although neurotrophins are widely expressed in the central nervous syst...

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Section: Methodsmentioning

confidence: 99%

Ovarian brain-derived neurotrophic factor (BDNF) promotes the development of oocytes into preimplantation embryos

Kawamura

Mulders

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

168

126

View full text Add to dashboard Cite

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“…The former are linked to neurotrophins and growth factors, whereas the latter are a component of the intracellular signaling cascade. Having established that a broad-spectrum inhibitor of PTKs prevents the induction of LTP GABA-A , we next investigated the effect of k-252a, a more specific inhibitor of PTKs coupled to Trk receptor family (Knusel and Hefti, 1992;Ross et al, 1995). k-252a (100 nM) was bath applied for 10 -15 min before DPs, during DPs, and 5-10 min after DPs for a total time of 20 -30 min.…”

Section: Role Of Trk Receptor-coupled Ptks In the Induction Of Gabaermentioning

confidence: 99%

Endogenous Neurotrophins Are Required for the Induction of GABAergic Long-Term Potentiation in the Neonatal Rat Hippocampus

Gubellini¹

2005

Journal of Neuroscience

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In the developing rat hippocampus, GABAergic synapses undergo a Ca 2ϩ -dependent long-term potentiation (LTP GABA-A ); this form of synaptic plasticity is induced in CA3 pyramidal neurons by delivering repetitive depolarizing pulses (DPs) to the recorded neuron, and it is expressed as a long-lasting increase in the frequency and amplitude of spontaneous GABA A receptor-mediated postsynaptic currents. In the present study, we examined the role of endogenous tropomyosin-related kinase receptor B (TrkB) receptor ligands and associated protein tyrosine kinases (PTKs) in the induction of LTP GABA-A . The application of Lavendustin A, a broad spectrum PTK inhibitor, blocked the induction of LTP GABA-A , whereas Lavendustin B, its inactive form, had no effect. Moreover, k-252a and k-252b, two alkaloids that inhibit the kinase activity of the Trk receptor family, also prevented the induction of LTP GABA-A . On hippocampal slices incubated with the soluble form of TrkB receptor IgG (TrkB-IgG), which prevents the activation of TrkB receptors by endogenous ligands, DPs failed to induce LTP GABA-A , whereas the incubation with TrkA-IgG or TrkC-IgG had no such effect. Altogether, these data indicate that endogenous TrkB ligands and associated PTK activity are necessary for the induction of GABAergic LTP in the developing rat hippocampus.

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“…23, but see also ref. 24). At 13 ng͞ml, 29 nM, this inhibitor blocked the conversion of NMDAR-only synapses into AMPAR-transmissible ones without affecting NMDAR transmission (Fig.…”

Section: Ampar Trafficking As An Essentialmentioning

confidence: 99%

Brain-derived neurotrophic factor-dependent unmasking of “silent” synapses in the developing mouse barrel cortex

Itami

Kimura

Kohno

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

106

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Brain-derived neurotrophic factor (BDNF) is a critical modulator of central synaptic functions such as long-term potentiation in the hippocampal and visual cortex. Little is known, however, about its role in the development of excitatory glutamatergic synapses in vivo. We investigated the development of N-methyl-D-aspartate (NMDA) receptor (NMDAR)-only synapses (silent synapses) and found that silent synapses were prominent in acute thalamocortical brain slices from BDNF knockout mice even after the critical period. These synapses could be partially converted to ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-containing ones by adding back BDNF alone to the slice or fully converted to together with electric stimulation without affecting NMDAR transmission. Electric stimulation alone was ineffective under the BDNF knockout background. Postsynaptically applied TrkB kinase inhibitor or calcium-chelating reagent blocked this conversion. Furthermore, the AMPAR C-terminal peptides essential for interaction with PDZ proteins postsynaptically prevented the unmasking of silent synapses. These results suggest that endogenous BDNF and neuronal activity synergistically activate AMPAR trafficking into synaptic sites.

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Differential Biological Effects of K252 Kinase Inhibitors Are Related to Membrane Solubility but Not to Permeability

Cited by 26 publications

References 14 publications

Ovarian brain-derived neurotrophic factor (BDNF) promotes the development of oocytes into preimplantation embryos

Ovarian brain-derived neurotrophic factor (BDNF) promotes the development of oocytes into preimplantation embryos

Endogenous Neurotrophins Are Required for the Induction of GABAergic Long-Term Potentiation in the Neonatal Rat Hippocampus

Brain-derived neurotrophic factor-dependent unmasking of “silent” synapses in the developing mouse barrel cortex

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