References

Chan A, Tsourkas A (2024) Intracellular protein delivery: Approaches, challenges, and clinical applications. BME Frontiers doi: 10.34133/bmef.0035

Objective: To review progress made towards achieving cytosolic delivery of recombinant proteins and possible strategies to enable proteins to cross cell membranes.

Summary: Drug delivery researchers have worked to deliver saporin into tumor cells in the hopes of producing potent next-generation cancer therapeutics. Cationic, anionic, and zwitterionic versions of poly(β-amino ester) have been developed for delivery of saporin. Chemically-modified saporin can be encapsulated by cationic LNPs for in vivo tumor inhibition. Saporin has been used as a model cargo protein for in vivo delivery via fluoropolymer nanoparticles for successful tumor growth inhibition.

Related Products: Saporin (Cat. #PR-01)

See Also:

• Ancheta LR et al. Saporin as a commercial reagent: its uses and unexpected impacts in the biological sciences-tools from the plant kingdom. Toxins (Basel) 14(3):184, 2022.

de Paula FS (2023) Immunomodulatory impact of memory T lymphocyties in periodontitis. Univ Minnesota Thesis.

Objective: This thesis paper sought to determine whether local reactivation of oral tissue resident memory cells (TRM) of a defined antigen specificity could exacerbate ligature-induced periodontal (LIP), a model for periodontal disease in mice.

Summary: Reactivation of oral TRM aggravated alveolar bone loss and amplified gingival and cervical lymph node (cLN) inflammation. Furthermore, oral TRM reactivation enhanced transcriptional changes in pro-inflammatory and periodontitis-related genes. Therapeutic depletion of CD103-expressing oral TRM in advanced of LIP mitigated alveolar bone loss and associated gingiva and cLN inflammation. The study provides evidence that local reactivation of oral TRM can potentiate periodontitis.

Usage: Anti-CD103-SAP (IT-50) was administered in mice via i.p. injection (7 ug in PBS).

Related Products: Anti-CD103-SAP (Cat. #IT-50)

Loftén A, Adermark L, Ericson M, Söderpalm B (2023) Regulation of ethanol-mediated dopamine elevation by glycine receptors located on cholinergic interneurons in the nucleus accumbens. Addict Biol 28(12):e13349. doi: 10.1111/adb.13349 PMID: 38017639

Objective: The aim of this study was to explore the role of glycine receptors (GlyRs) on cholinergic interneurons (CIN) in sustaining extracellular dopamine levels and in ethanol-induced dopamine release.

Summary: Alcohol use disorder is one of the major psychiatric disorders worldwide. Ethanol reward is one of the many factors contributing to the disorder. The rewarding and reinforcing properties of ethanol have been linked to activation of the mesolimbic dopamine system, an effect that involves glycine receptors (GlyRs) in the nucleus accumbens. The study suggests that CIN are not important for GlyR-mediated regulation of basal dopamine output, but that CIN ablation blunts the ethanol-induced dopamine release by reducing the release of GlyR agonists.

Usage: CIN were ablated by Anti-ChAT-SAP administered locally in the nucleus accumbens of male Wistar rats. Rabbit-IgG-SAP was used as a control. Microinfusion was performed unilaterally into the nAc at a concentration of 0.5 ug/ul at 0.05 ul/min for 10 min for a total of 0.5 ul.

Related Products: Anti-ChAT-SAP (Cat. #IT-42), Rabbit IgG-SAP (Cat. #IT-35)

Takanami K, Kuroiwa M, Ishikawa R, Imai Y, Oishi A, Hashino M, Shimoda Y, Sakamoto H, Koide T (2023) Function of gastrin-releasing peptide receptors in ocular itch transmission in the mouse trigeminal sensory system. Front Mol Neurosci 16:1280024. doi: 10.3389/fnmol.2023.1280024 PMID: 38098939

Objective: To investigate the role of gastrin-releasing peptide (GRP) and GRP receptor (GRPR) in itch transmission in the spinal somatosensory system, and to determine whether the GRP system is involved in itch neurotransmission of the eyes in the trigeminal sensory system

Summary: Administering itch mediators like histamine (His) and chloroquine (CQ) caused high levels of eye scratching in a concentration-dependent manner, with significant gender differences observed for His. Histological studies showed that His and CQ significantly activated GRPR-expressing neurons in a specific brain region of transgenic mice. Blocking these neurons with a GRPR antagonist or eliminating them reduced CQ-induced scratching. Injecting a GRPR agonist without an itch stimulus led to excessive facial scratching, indicating the central role of GRPR neurons in mediating itch responses.

Usage: 500 ng Blank-SAP (IT-21) or 500 ng Bombesin-SAP (IT-40) were intracisternally administered (5-uL volume) 2 weeks prior to behavioral experiments.

Related Products: Bombesin-SAP (Cat. #IT-40), Blank-SAP (Cat. #IT-21)

Chamberlain AR, Huynh L, Huang W, Taylor DJ, Harris ME (2023) The specificity landscape of bacterial ribonuclease P. J Biol Chem 300(1):105498. doi: 10.1016/j.jbc.2023.105498 PMID: 38013087

Objective: Review of the specificity of ribonucleoprotein RNase P in binding different types of RNA.

Summary: Ribonucelase P is involved in the RNA metabolism pathways. By studying the rate at which it combines with different types of RNA under different conditions, like concentration and competition with different enzymes, a model describing its specificity to different RNA motifs can be developed.

Related Products: Saporin (Cat. #PR-01)

See Also:

• Hauf, S., Rotrattanadumrong, R., and Yokobayashi, Y. (2022) Analysis of the sequence preference of saporin by deep sequencing. ACS Chem. Biol.17, 2619–2630

Münzberg H, Berthoud HR, Neuhuber WL (2023) Sensory spinal interoceptive pathways and energy balance regulation. Mol Metab 78:101817. doi: 10.1016/j.molmet.2023.101817 PMID: 37806487

Objective: To review and discuss the roles of spinal sensory pathways, specifically dorsal root ganglia (DRG) afferents, in energy balance regulation, highlighting their contributions to metabolic homeostasis in health and disease.

Summary: This comprehensive review explores the emerging significance of spinal sensory neurons, beyond traditional gut-brain and adipose tissue-to-brain signaling pathways, in regulating energy intake and metabolism. It delves into the anatomy and functions of spinal sensory pathways, emphasizing the potential of DRG afferents in providing metabolic information to the brain. The review suggests that identifying specific DRG neurons and understanding their molecular mechanisms are crucial steps toward developing targeted therapies for metabolic diseases, such as obesity, diabetes, and cancer.

Usage: The publication references that CCK-SAP (IT-31) injected into the nodose ganglia of mice and rats selectively ablates vagal afferent neurons expressing CCKA receptors.

Related Products: CCK-SAP (Cat. #IT-31)

See Also:

• Diepenbroek C et al. Validation and characterization of a novel method for selective vagal deafferentation of the gut. Am J Physiol Gastrointest Liver Physiol 313:G342-G352, 2017.

Campideli-Santana AC, da Costa Silva KS, Araújo-Lopes R, Antunes LM, Szawka RE (2023) Submaximal loss of KNDy neurons accelerates and amplifies pulsatile LH secretion in female rats. J Endocrine Society 7(S1):bvad114.1214. doi: 10.1210/jendso/bvad114.1214

Objective: To investigate the impact of the submaximal loss of KNDy neurons on the pulsatile secretion of luteinizing hormone (LH) in female rats.

Summary: The study found that a partial loss of these neurons led to irregular estrous cycles and increased frequency and amplitude of LH pulses. This suggests a new role for KNDy neurons in moderating LH pulse frequency and amplitude in ovary-intact animals, with implications for early antral follicle recruitment.

Usage: Adult female rats underwent a neurochemical ablation of KNDy neurons via intra-ARC stereotaxic injections of NKB-SAP (IT-63), while control animals received Blank-SAP (IT-21).

Related Products: NKB-SAP (Cat. #IT-63), Blank-SAP (Cat. #IT-21)

Aquino NSS, Campideli-Santana AC, Antunes LM, Araújo-Lopes R, da Costa Silva KS, Costa Henriques P, de Oliveira Gusmão D, Bernuci MP, Szawka RE, dos Reis AM (2023) Partial loss of KNDy neurons in prenatally androgen treated female rats alters the LH secretion and ovarian morphology in a model of polycystic ovary syndrome. J Endocrine Society 7(S1):bvad114.1215. doi: 10.1210/jendso/bvad114.1215

Objective: To examine the impact of partial loss of KNDy neurons in prenatally androgen-treated female rats on luteinizing hormone (LH) secretion and ovarian morphology, as a model of polycystic ovary syndrome (PCOS).

Summary: The study found that the ablation of KNDy neurons resulted in increased LH pulse amplitude and mean LH levels without affecting pulse frequency, and partially restored the number of primordial follicles, suggesting KNDy neurons’ role in modulating LH release and ovarian reserve in PCOS.

Usage: Intra-ARC stereotaxic injections of the neurokinin-3 receptor agonist conjugated with Saporin (NKB-SAP, IT-63) to induce the lesion of KNDy neurons. Blank-SAP (IT-21) was used as a control.

Related Products: NKB-SAP (Cat. #IT-63), Blank-SAP (Cat. #IT-21)

Goodman RL, Moore AM, Onslow K, Hileman SM, Hardy SL, Bowdridge EC, Walters BA, Agus S, Griesgraber MJ, Aerts EG, Lehman MN, Coolen LM (2023) Lesions of kndy and kiss1r neurons in the arcuate nucleus produce different effects on lh pulse patterns in female sheep. Endocrinology 164(11):bqad148. doi: 10.1210/endocr/bqad148 PMID: 37776515

Objective: To test the functional role of ovine KNDy neurons in pulse generation and identify the roles of nearby Kiss1 receptor (Kiss1R)-containing cells.

Summary: Injection of NK3-SAP (NKB-SAP) ablated over 90% of the KNDy cells, Kiss-SAP lesioned about two-thirds of the Kiss1R population. This led to a significant decrease in LH pulse amplitude and altering LH pulse patterns. NK3-SAP increased the interpulse interval without affecting the regularity of LH pulses, whereas Kiss-SAP disrupted their regular hourly occurrence but not the interpulse interval. The findings suggest that KNDy neurons are critical for GnRH pulse generation in ewes, while ARC Kiss1R cells support the amplitude and regularity of these pulses, possibly as part of a positive feedback loop involving GABA or glutamate.

Usage: Saporin conjugates were injected into the arcuate nucleus. Kiss-SAP (kisspeptin54-SAP) was diluted to 700 ng/μL in PBS immediately before use. In preliminary work to test the effectiveness of Kiss-SAP, a single unilateral injection (1 μL of 700 ng/μL) of this conjugate was made in the preoptic area of 3 ewes. The contralateral side was used as control and either received no injections or Blank-SAP (1 μL of 700 ng/μL) (IT-21).

Related Products: NKB-SAP (Cat. #IT-63), Blank-SAP (Cat. #IT-21)

Gao Q, Zhang Y, Wang X, Wang R, Zhang L (2024) Regulation of nociception threshold by norepinephrine through adrenergic α2 receptor in rat models of Parkinson’s disease. CNS Neurosci Ther 30(3):e14446. doi: 10.1111/cns.14446 PMID: 37721421

Objective: To investigate the effect of norepinephrine on the activation of brain cells through adrenergic α2 receptor, to regulate the nociception threshold in a 6-OHDA-induced animal model of Parkinson’s disease (PD).

Summary: The change of norepinephrine content can affect the activation of prefrontal and cingulate gyrus glial cells and participate in the regulation of nociception threshold in PD rats. Adrenergic α2 receptor agonist and central presynaptic membrane α2 receptor blocker both affect cell activation and improve hyperalgesia.

Usage: 4 μL of Anti-DBH-saporin was injected into the right lateral ventricle (1.25 μg/μL, 0.9% NaCl dilution), and injected at the rate of 1 μL/min.

Related Products: Anti-DBH-SAP (Cat. #IT-03)