Immunologic localization and kinetic characterization of a Na+/Ca2+ exchanger in neuronal and non-neuronal cells

Michaelis, Mary L.; Walsh, Julie L.; Pal, Ranu; Hurlbert, Marc; Hoel, Gary; Bland, Kimberly S.; Foye, J.; Kwong, Wing Hang

doi:10.1016/0006-8993(94)91187-8

Cited by 19 publications

(24 citation statements)

References 25 publications

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“…Dissociated cortical cell cultures were established from embryonic day 18 rat fetuses recovered from pregnant Sprague-Dawley rats (Harlan, Indianapolis, IN) as described previously (Michaelis et al, 1994). Pups were delivered by cesarean section while the dam was anesthetized with pentobarbital (140 mg/kg i.p.…”

Section: Methodsmentioning

confidence: 99%

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β-Amyloid-Induced Neurodegeneration and Protection by Structurally Diverse Microtubule-Stabilizing Agents

Michaelis

Ansar

Chen

et al. 2004

J Pharmacol Exp Ther

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Deposition of ␤-amyloid peptide (A␤) and hyperphosphorylation of the protein are associated with neuronal dysfunction and cell death in Alzheimer's disease. Although the relationship between these two processes is not yet understood, studies have shown that both in vitro and in vivo exposure of neurons to A␤ leads to hyperphosphorylation and neuronal dystrophy. We previously reported that the microtubule-stabilizing drug paclitaxel (Taxol) protects primary neurons against toxicity induced by the A␤ [25][26][27][28][29][30][31][32][33][34][35] peptide. The studies in this report were undertaken to characterize the actions of paclitaxel more fully, to assess the effectiveness of structurally diverse microtubulestabilizing agents in protecting neurons, and to determine the time course of the protective effects of the drugs. Primary neurons were exposed to A␤ in the presence or absence of several agents shown to interact with microtubules, and neuronal survival was monitored. Paclitaxel protected neurons against A␤ 1-42 toxicity, and paclitaxel-treated cultures exposed to A␤ showed enhanced survival over A␤-only cultures for several days. Neuronal apoptosis induced by A␤ was blocked by paclitaxel. Other taxanes and three structurally diverse microtubule-stabilizing compounds also significantly increased survival of A␤-treated cultures. At concentrations below 100 nM, the drugs that protected the neurons did not produce detectable toxicity when added to the cultures alone. Although multiple mechanisms are likely to contribute to the neuronal cell death induced by oligomeric or fibrillar forms of A␤, low concentrations of drugs that preserve the integrity of the cytoskeletal network may help neurons survive the toxic cascades initiated by these peptides.

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Section: Methodsmentioning

confidence: 99%

“…Serum-containing medium was removed after 24 h, and the cells were maintained in serum-free Dulbecco's modified Eagle's medium/F-12 containing the N 2 supplements. Cultures were grown at 37°C in 5% CO 2 and 97% humidity as described (Michaelis et al, 1994).…”

Section: Methodsmentioning

confidence: 99%

β-Amyloid-Induced Neurodegeneration and Protection by Structurally Diverse Microtubule-Stabilizing Agents

Michaelis

Ansar

Chen

et al. 2004

J Pharmacol Exp Ther

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“…Dissociated cortical cell cultures were established from embryonic day 18 rat fetuses recovered from pregnant Sprague-Dawley rats (Harlan Sprague Dawley Inc., Indianapolis, IN) as described previously [18]. After the final precipitation step, neurons were suspended in fresh Dulbecco's modified Eagle's medium/F-12 with 10% fetal bovine serum (Atlanta Biologicals, Lawrenceville, GA) and plated at a density of 2.5 x 10 5 cells in 35 mm glass bottom microwell dishes (MatTek Co., Ashland, MA), coated with poly-D-lysine.…”

Section: Neuronal Cell Culturesmentioning

confidence: 99%

“…Serum-containing medium was removed after 24 h, and the cells were maintained in serum-free Dulbecco's modified Eagle's medium/F-12 containing the N2 supplements. Cultures were grown at 37 °C in 5% CO 2 and 97% humidity as previously described [18].…”

Section: Neuronal Cell Culturesmentioning

confidence: 99%

TCP-FA4: A derivative of tranylcypromine showing improved blood–brain permeability

Desino

Pignatello

Guccione

et al. 2009

Biochemical Pharmacology

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(S. Guccione). ¥ This work is part of K.E. D. PhD thesis. A variety of approaches have been taken to improve the brain penetration of pharmaceutical agents. The amphipathic character of a compound can improve its interaction with the lipid bilayer within cell membranes, and as a result improve permeability. Fatty acid chains or lipoamino acids of various lengths were attached to tranylcypromine (TCP), in an attempt to improve the blood-brain barrier (BBB) permeability by increasing the lipophilicity as well as the amphiphatic character of the drug. TCP-FA4, one of the derivatives containing a four carbon alkyl acid chain, showed the greatest improvement in permeability. This molecule was slightly neuroprotective in a β-amyloid induced neurodegeneration assay and may also be capable of upregulating brain derived neurotrophic factor (BDNF), as indicated by cell culture assays using human umbilical vein endothelial cells. Since decreased levels of BDNF are observed in many CNS disorders, and direct injection of BDNF is not a viable option due to its poor permeability across the BBB, small molecules capable of regulating BDNF that also cross the BBB may be an interesting treatment option.

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“…Taxol was purchased from Dabur India, Ltd. and the succinylated taxol analog (JX67) was prepared by parallel solution phase synthesis (Liu et al 2002). Histone HI, bovine brain tau, N-succinyl-leu-tyr-7-amido-4-methylooumarin, and APi_42 peptides were purchased from Sigma/Aldrich Chemicals (St Louis, MO, USA Cell culture and drug administration Primary cortical neurons were prepared from embryonic day 18 Sprague-Dawley rat pups as described previously (Michaelis et al 1994). Following trituration, the cells were resuspended in Dulbecco's modified Eagle's medium/F12 (DMEM/FI2) containing 15 mM KHCO3, 10% fetal calf serum and plated onto 35 or 60 mm poly D-lysine-coated dishes at a density of 6.5 x lO' or 2x10^ cells/dish for viability and biochemical assays, respectively.…”

Section: Methodsmentioning

confidence: 99%

The Design, Synthesis, and Biological Evaluation of New Paclitaxel Analogs With the Ability to Evade Efflux by P-Glycoprotein

Turunen¹

2005

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Immunologic localization and kinetic characterization of a Na+/Ca2+ exchanger in neuronal and non-neuronal cells

Cited by 19 publications

References 25 publications

β-Amyloid-Induced Neurodegeneration and Protection by Structurally Diverse Microtubule-Stabilizing Agents

β-Amyloid-Induced Neurodegeneration and Protection by Structurally Diverse Microtubule-Stabilizing Agents

TCP-FA4: A derivative of tranylcypromine showing improved blood–brain permeability

The Design, Synthesis, and Biological Evaluation of New Paclitaxel Analogs With the Ability to Evade Efflux by P-Glycoprotein

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