I1 imidazoline receptor-mediated effects on apoptotic processes in PC12 cells

Dupuy, Laurence; Urosevic, Dragan; Greney, Hugues; Quaglia, Wilma; Pigini, Maria; Brasili, Livio; Dontenwill, Monique; Bousquet, Pascal

doi:10.1038/sj.cdd.4401447

Cited by 18 publications

(14 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Secondly, transfection of IRAS cDNA into CHO cells resulted in high affinity I1-like binding sites without the appearance of a2 adrenergic receptors or the other major subtype of imidazoline binding sites (Piletz et al 2000(Piletz et al , 2003. Thirdly, it has been revealed that IRAS could promote cell survival, anti-apoptosis, and proliferation (Dontenwill et al 2003a, b;Sano et al 2002), which is similar to the intracellular functions of I1 imidazoline receptor (Dupuy et al 2004). Most importantly, our recent study showed that the signal transduction pathway coupled to IRAS was similar to that coupled to I1 imidazoline receptor , which is crucial to the identity of cloned IRAS and native I1 imidazoline receptor.…”

Section: The Identity Between Cloned Iras and Native I1 Imidazoline Rmentioning

confidence: 95%

Agmatine and Imidazoline Receptors: Their Role in Opioid Analgesia, Tolerance and Dependence

Wu¹,

Su²,

Jin³

2007

Cell Mol Neurobiol

View full text Add to dashboard Cite

Agmatine is an endogenous amine that is synthesized following the decarboxylation of L-arginine by arginine decarboxylase. Agmatine exists in mammalian brain and has been proposed as a neurotransmitter and/or neurotransmodulator. Agmatine binds to several targets and is considered as an endogenous ligand for imidazoline receptors. This review, mainly based on our research work in the past decade, focused on the modulations by agmatine action on imidazoline receptors to opioid analgesia, tolerance and dependence, and its possible neurochemical mechanisms. We went on to propose that agmatine and imidazoline receptors constitute a novel system of modulating opioid functions.

show abstract

Section: The Identity Between Cloned Iras and Native I1 Imidazoline Rmentioning

confidence: 95%

Agmatine and Imidazoline Receptors: Their Role in Opioid Analgesia, Tolerance and Dependence

Wu¹,

Su²,

Jin³

2007

Cell Mol Neurobiol

View full text Add to dashboard Cite

show abstract

“…Here, we further investigated the effect of TVP1022 on MAPK signaling pathway known to be coupled to I 1 imidazoline receptor in PC12 cells [16], [17], [18]. This cell line provides the predominant cellular model for investigating I 1 imidazoline receptor signaling [16].…”

Section: Resultsmentioning

confidence: 99%

“…As shown in Figure 2B, pretreatment with PD98059 (30 µM) significantly blocked the effect of TVP1022-induced increase of MAPK phosphorylation.The activation of p42/44 MAPK was determined as the ratio of the amount of the dually phosphorylated active form to total MAPK immunoreactivity. In addition, to analyze whether the effect of TVP1022 on MAPK stimulation was mediated by the I 1 imidazoline receptor, we used efaroxan, a selective I 1 imidazoline receptor antagonist [18]. As depicted in Figure 2B, efaroxan (10 µM) abolished the effect of TVP1022 on MAPK activation, suggesting the involvement of I 1 imidazoline receptor in TVP1022-induced MAPK activation.…”

Section: Resultsmentioning

confidence: 99%

I1 Imidazoline Receptor: Novel Potential Cytoprotective Target of TVP1022, the S-Enantiomer of Rasagiline

et al. 2012

View full text Add to dashboard Cite

TVP1022, the S-enantiomer of rasagiline (Azilect®) (N-propargyl-1R-aminoindan), exerts cyto/cardio-protective effects in a variety of experimental cardiac and neuronal models. Previous studies have demonstrated that the protective activity of TVP1022 and other propargyl derivatives involve the activation of p42/44 mitogen-activated protein kinase (MAPK) signaling pathway. In the current study, we further investigated the molecular mechanism of action and signaling pathways of TVP1022 which may account for the cyto/cardio-protective efficacy of the drug. Using specific receptor binding and enzyme assays, we demonstrated that the imidazoline 1 and 2 binding sites (I1 & I2) are potential targets for TVP1022 (IC50 = 9.5E-08 M and IC50 = 1.4E-07 M, respectively). Western blotting analysis showed that TVP1022 (1–20 µM) dose-dependently increased the immunoreactivity of phosphorylated p42 and p44 MAPK in rat pheochromocytoma PC12 cells and in neonatal rat ventricular myocytes (NRVM). This effect of TVP1022 was significantly attenuated by efaroxan, a selective I1 imidazoline receptor antagonist. In addition, the cytoprotective effect of TVP1022 demonstrated in NRVM against serum deprivation-induced toxicity was markedly inhibited by efaroxan, thus suggesting the importance of I1imidazoline receptor in mediating the cardioprotective activity of the drug. Our findings suggest that the I1imidazoline receptor represents a novel site of action for the cyto/cardio-protective efficacy of TVP1022.

show abstract

“…hIRAS is a larger protein of 1504 amino acids consisting of an NH 2 -terminal phox (PX) domain, 5 putative leucine-rich repeats, a predicted coiledcoil domain, and a long COOH-terminal region. Several evidence supported the identity of native I1R and IRAS protein in tissue distributions, ligand binding properties, some cellular functions and downstream signal pathways [14][15][16][17][18]. The murine form of IRAS, Nischarin, truncated at the N-terminal 244 amino acids including the PX domain compared with the hIRAS, was a soluble cytosolic protein involved in cytoskeletal organization [19].…”

mentioning

confidence: 89%

Generation and Characterization of Novel Human IRAS Monoclonal Antibodies

Wang¹,

Liu²,

Shan³

et al. 2009

BioMed Research International

View full text Add to dashboard Cite

Imidazoline receptors were first proposed by Bousquet et al., when they studied antihypertensive effect of clonidine. A strong candidate for I1R, known as imidazoline receptor antisera-selected protein (IRAS), has been cloned from human hippocampus. We reported that IRAS mediated agmatine-induced inhibition of opioid dependence in morphine-dependent cells. To elucidate the functional and structure properties of I1R, we developed the newly monoclonal antibody against the N-terminal hIRAS region including the PX domain (10–120aa) through immunization of BALB/c mice with the NusA-IRAS fusion protein containing an IRAS N-terminal (10–120aa). Stable hybridoma cell lines were established and monoclonal antibodies specifically recognized full-length IRAS proteins in their native state by immunoblotting and immunoprecipitation. Monoclonal antibodies stained in a predominantly punctate cytoplasmic pattern when applied to IRAS-transfected HEK293 cells by indirect immunofluorescence assays and demonstrated excellent reactivity in flow immunocytometry. These monoclonal antibodies will provide powerful reagents for the further investigation of hIRAS protein functions.

show abstract

I1 imidazoline receptor-mediated effects on apoptotic processes in PC12 cells

Cited by 18 publications

References 5 publications

Agmatine and Imidazoline Receptors: Their Role in Opioid Analgesia, Tolerance and Dependence

Agmatine and Imidazoline Receptors: Their Role in Opioid Analgesia, Tolerance and Dependence

I1 Imidazoline Receptor: Novel Potential Cytoprotective Target of TVP1022, the S-Enantiomer of Rasagiline

Generation and Characterization of Novel Human IRAS Monoclonal Antibodies

Contact Info

Product

Resources

About