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Cannabinoid receptors and glial response following a basal forebrain cholinergic lesion
Llorente-Ovejero A, Bengoetxea de Tena I, Martínez-Gardeazabal J, Moreno-Rodríguez M, Lombardero L, Manuel I, Rodríguez-Puertas R (2022) Cannabinoid receptors and glial response following a basal forebrain cholinergic lesion. ACS Pharmacol Transl Sci 5(9):791-802. doi: 10.1021/acsptsci.2c00069 PMID: 36110372
Objective: The endocannabinoid system is involved in the control of learning, memory, and neuroinflammatory processes and plays a role in neurodegeneration, such as in Alzheimer’s disease (AD). The objective was to study the roles of cannabinoid receptors in the regulation of neuroinflammation.
Summary: Selective agonists and antagonists to the cannabinoid receptors CB1 and CB2 were studied for their binding to G-proteins after specific lesioning of the basal forebrain cholinergic neurons (BCFN) using 192-IgG-SAP. These neurons are the same cholinergic pathways that are lost in the early stages of Alzheimer’s disease (AD). In their study, an increase of microglia immunoreactivities (GFAP and Iba-1) and decrease of astrocyte immunoreactivities were seen which indicate microglia-mediated neuroinflammation. In cortical BFCN projection areas, CB1 receptor binding to Gi/o-proteins was upregulated and at the injection site, the area that showed the highest increase of microglia, only slight CB2 binding to Gi/o-proteins were detected. Dose: Rats received 135 ng/μLof 192IgG-saporin (1μL/hemisphere; 0.25μL/min).
Related Products: 192-IgG-SAP (Cat. #IT-01)
Long-term nucleus basalis cholinergic depletion induces attentional deficits and impacts cortical neurons and BDNF levels without affecting the NGF synthesis
Orciani C, Hall H, Pentz R, Foret MK, Do Carmo S, Cuello AC (2022) Long-term nucleus basalis cholinergic depletion induces attentional deficits and impacts cortical neurons and BDNF levels without affecting the NGF synthesis. J Neurochem 163(2):149-167. doi: 10.1111/jnc.15683 PMID: 35921478
Objective: To determine whether reciprocal interaction of basal forebrain cholinergic neurons (BFCN) impact neurotrophin availability and affect cortical neuronal markers.
Summary: There is a neuroprotective role of cholinergic neurotransmission in the adult, fully-differentiated cortex.
Usage: Immunolesioned BFCN projecting mainly to the cortex with 192-IgG-SAP (bilateral 0.5 ug/ul; 1.0 ul/hemisphere) in 2.5 month-old Wistar rats.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Stimulation of Akt phosphorylation and glucose transport by metalloporphyrins with peroxynitrite decomposition catalytic activity
Eccardt AM, Pelzel RJ, Bell TP, Fisher JS (2022) Stimulation of Akt phosphorylation and glucose transport by metalloporphyrins with peroxynitrite decomposition catalytic activity. Catalysts 12(8):849. doi: 10.3390/catal12080849 PMID: 37123089
Objective: To determine whether a catalytic action of iron porphyrin compounds would be related to their stimulation of insulin signaling and glucose uptake in C2C12 myotubes.
Summary: Findings suggest that iron porphyrin compounds with both peroxynitrite decomposition activity and peroxidase activity can stimulate insulin signaling and glucose transport in skeletal muscle cells.
Usage: Western blot
Related Products: NO-L-Cysteine Mouse Monoclonal, Conjugated (Cat. #AB-T125)
Perinatal correlated retinal activity is required for the wiring of visual axons in non-image forming nuclei
Negueruela S, Morenilla C, Herrera M, Coca Y, Florez-Paz D, López-Cascales MT, Gomis A, Herrera E (2022) Perinatal correlated retinal activity is required for the wiring of visual axons in non-image forming nuclei. bioRxiv 2022.07.27.501692. doi: 10.1101/2022.07.27.501692
Related Products: Melanopsin Rabbit Polyclonal (Cat. #AB-N38)
Differential role of GABAergic and cholinergic ventral pallidal neurons in behavioral despair, conditioned fear memory and active coping.
Akmese C, Sevinc C, Halim S, Unal G (2022) Differential role of GABAergic and cholinergic ventral pallidal neurons in behavioral despair, conditioned fear memory and active coping. bioRxiv 2022.07.21.500949. doi: 10.1101/2022.07.21.500949
Related Products: 192-IgG-SAP (Cat. #IT-01), GAT1-SAP (Cat. #IT-32)
Saporin toxin delivered by engineered colloidal nanoparticles is strongly effective against cancer cells
Salvioni L, Testa F, Barbieri L, Giustra M, Bertolini JA, Tomaino G, Tortora P, Prosperi D, Colombo M (2022) Saporin toxin delivered by engineered colloidal nanoparticles is strongly effective against cancer cells. Pharmaceutics 14(7):1517. doi: 10.3390/pharmaceutics14071517 PMID: 35890411
Objective: Using Saporin-containing iron oxide nanoparticles to selectively eliminate cancer cells.
Summary: Saporin [PR-01] is trapped inside of nanoparticle using iron oxide and polymers that opens and delivers payload dependent on its pH enviroment. The nanoparticle-SAP was then treated on healthy and cancerous cells and tested for its selectivity in killing cancerous cells and its internalization efficiency.
Usage: An iron oxide nanoparticle is coated in an amphiphilic polymer, then linker groups are attached to the polymer coating which then bind saporin molecules to the nanoparticle. In the cytotoxicity assays, SK-Br-3 cells are treated with this nanoparticle at concentrations of 25, 37.5, and 50 μg/mL. In internalization assays, SK-Br-3 cells are treated with fluorescently-labeled saporin-nanoparticles and assessed on fluorescence intensity.
Related Products: Saporin (Cat. #PR-01)
A century searching for the neurons necessary for wakefulness
Grady FS, Boes AD, Geerling JC (2022) A century searching for the neurons necessary for wakefulness. Front Neurosci 16:930514. doi: 10.3389/fnins.2022.930514
Objective: This review article attempts to summarize research that has investigated the neurons necessary for wakefulness.
Summary: The authors summarize animal experiments and research performed in different brain regions to further understand wakefulness. Several saporin conjugates are discussed.
Usage: Lesions of the basal forebrain were done by injecting a 0.1% solution of either 192-IgG-SAP or Orexin-SAP at four different sites (Fuller et al. and Geraschenko et al.); Intraventricular injection of Anti-DBH-SAP (Gompf et al.); Bilateral injections of 192-IgG-SAP (Kaur et al.).
Related Products: Orexin-B-SAP (Cat. #IT-20)
See Also:
- Fuller P et al. Reassessment of the structural basis of the ascending arousal system. J Comp Neurol 519(5):933-956, 2011.
- Gerashchenko D et al. Insomnia following hypocretin2-saporin lesions of the substantia nigra. Neuroscience 137(1):29-36, 2006.
- Gompf HS et al. Locus ceruleus and anterior cingulate cortex sustain wakefulness in a novel environment. J Neurosci 30(43):14543-14551, 2010.
- Kaur S et al. Effects of ibotenate and 192IgG-saporin lesions of the nucleus basalis magnocellularis/substantia innominata on spontaneous sleep and wake states and on recovery sleep after sleep deprivation in rats. J Neurosci 28:491-504, 2008.
RIPpore: A novel host-derived method for the identification of ricin intoxication through oxford nanopore direct RNA sequencing
Ryan Y, Harrison A, Trivett H, Hartley C, David J, Clark GC, Hiscox JA (2022) RIPpore: A novel host-derived method for the identification of ricin intoxication through oxford nanopore direct RNA sequencing. Toxins (Basel) 14(7):470. doi: 10.3390/toxins14070470 PMID: 35878208
Objective: The Depurination event could be detected using Oxford Nanopore Technologies (ONT) direct RNA sequencing, detecting a change in charge in the ricin loop.
Summary: Collectively, this work highlights the potential for ONT and direct RNA sequencing to detect and quantify depurination events caused by ribosome-inactivating proteins such as ricin.
Usage: Saporin was added as described by Rust et al., at 100 nM [22] for 24 h.
Related Products: Saporin (Cat. #PR-01)
See Also:
Antibody-based preparative regimens for cell, tissue and organ transplantation
Van Hentenryck M, Li Z, Murphy PM, Czechowicz A (2022) Antibody-based preparative regimens for cell, tissue and organ transplantation. (eds. 162). OBM Transplantation 6(3):162. doi: 10.21926/obm.transplant.2203162
Objective: Provide a review of progress in the use of antibodies to support cell and tissue transplantation with a particular focus on induction of donor-specific tolerance for solid organ transplantation.
Summary: Antibody-based conditioning to prepare the recipient is a promising approach towards achieving transplant tolerance in both hematopoietic and solid organ transplant settings.
Usage: To enhance HSC depletion while avoiding bystander toxicity (neutropenia, lymphopenia, and thrombocytopenia) caused by CD45-radioimmunotherapy, Palchaudhuri et al. developed a saporin-based CD45 (CD45-SAP) immunotoxin using a biotinylated antibody and Streptavidin-ZAP.
Related Products: Streptavidin-ZAP (Cat. #IT-27)
See Also:
- Palchaudhuri R Featured Article: Targeted depletion of hematopoietic stem cells promises safer transplantation. Targeting Trends 17(3), 2016.
- Palchaudhuri R et al. Non-genotoxic conditioning for hematopoietic stem cell transplantation using a hematopoietic-cell-specific internalizing immunotoxin. Nat Biotechnol 34:738-745, 2016.
Synchronous intracellular delivery of EGFR-targeted antibody-drug conjugates by p38-mediated non-canonical endocytosis
Takahashi JI, Nakamura S, Onuma I, Zhou Y, Yokoyama S, Sakurai H (2022) Synchronous intracellular delivery of EGFR-targeted antibody-drug conjugates by p38-mediated non-canonical endocytosis. Sci Rep 12(1):11561. doi: 10.1038/s41598-022-15838-8 PMID: 35798841
Objective: The binding of cetuximab to EGFR suppresses ligand-induced signaling events. The authors demonstrate that synchronous non-canonical EGFR endocytosis can increase the efficacy of EGFR-targeting ADCs.
Summary: Epidermal growth factor (EGFR) has been a popular target in the treatment of cancer via monoclonal antibodies, specifically cetuximab and panitumumab. They have been applied to antibody-drug conjugates (ADCs) and their clinical efficacy had been demonstrated, but this efficacy has also been limited by acquired resistance via secondary mutations or the activation of bypass pathways. To overcome these limiting factors, the authors investigated if non-canonical clathrin-mediated endocytosis (CME) of EGFR induced the internalization of membrane-bound EGFR-targeted mAbs. Their results show that tumor necrosis factor-alpha strongly induces endocytosis of the cetuximab-EGFR complex via the p38 phosphorylation of EGFR and that Hum-ZAP, a secondary antibody conjugated to saporin, will also undergo internalization with the complex and enhance anti-proliferative activity.
Related Products: Hum-ZAP (Cat. #IT-22)