Etorphine inhibits cell growth and induces apoptosis in SK-N-SH cells: involvement of pertussis toxin-sensitive G proteins

Yin, Deling; Ren, Xiuhai; Zheng, Zhenlin; Pu, Lu; Jiang, Li‐Yun; Ma, Lan; Pei, Gang

doi:10.1016/s0168-0102(97)00080-1

Cited by 54 publications

(29 citation statements)

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“…PTX-sensitive G-proteins have been implicated in the apoptotic death of neuronal cells (Yan et al, 1995;Yamatsuji et al, 1996;Wolozin et al, 1996;Yin et al, 1997;Farkas et al, 1998;Okazawa et al, 1998). Given that transfected G␤2␥2, but not ␣ subunits of PTX-sensitive G-proteins, induces DNA fragmentation in cultured cells (Giambarella et al, 1997), neurotoxicity of ApoE4 may occur through the G␤␥ subunit released from activated G i .…”

Section: Discussionmentioning

confidence: 99%

Neuronal Apoptosis by Apolipoprotein E4 through Low-Density Lipoprotein Receptor-Related Protein and Heterotrimeric GTPases

et al. 2000

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The ⑀4 genotype of apolipoprotein E (apoE4) is the most established predisposing factor in Alzheimer's disease (AD); however, it remains unclear how apoE4 contributes to the pathophysiology. Here, we report that the apoE4 protein (ApoE4) evokes apoptosis in neuronal cells through the low-density lipoprotein receptor-related protein (LRP) and heterotrimeric GTPases. We examined neuron/neuroblastoma hybrid F11 cells and found that these cells were killed by 30 g/ml ApoE4, but not by 30 g/ml ApoE3. ApoE4-induced death occurred with typical features for apoptosis in time-and dose-dependent manners, and was observed in SH-SY5Y neuroblastomas, but not in glioblastomas or non-neuronal Chinese hamster ovary cells. Activated, but not native, ␣2-macroglobulin suppressed this ApoE4 toxicity. Suppression by the antisense oligonucleotide to LRP and inhibition by low nanomolar concentrations of LRP-associated protein RAP provided evidence for the involvement of LRP. The involvement of heterotrimeric GTPases was demonstrated by the findings that (1) ApoE4-induced death was suppressed by pertussis toxin (PTX), but not by heat-inactivated PTX; and (2) transfection with PTX-resistant mutant cDNAs of G␣ i restored the toxicity of ApoE4 restricted by PTX. We thus conclude that one of the neurotoxic mechanisms triggered by ApoE4 is to activate a cell type-specific apoptogenic program involving LRP and the G i class of GTPases and that the apoE4 gene may play a direct role in the pathogenesis of AD and other forms of dementia.

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Section: Discussionmentioning

confidence: 99%

Neuronal Apoptosis by Apolipoprotein E4 through Low-Density Lipoprotein Receptor-Related Protein and Heterotrimeric GTPases

et al. 2000

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“…Opioid receptors have been shown to be involved in both apoptosis and cell survival [187][188][189][190][191][192][193][194][195]. Activation of MOR and KOR in embryonic stem cells, or MOR and DOR in adult hippocampal progenitor cells, promotes proliferation of these cells that is Erk1/2-dependent [77,193,196].…”

Section: Effectors Activated By the Bg Subunits Of G Proteinsmentioning

confidence: 99%

Opioid Receptor Signal Transduction Mechanisms

Law

2010

The Opiate Receptors

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The myriad functions of morphine and its congeners are the consequences of the drug interacting with the three opioid receptors. In order to develop a perfect analgesic compound that mediates its function via these receptors, the mechanisms by which signaling occurs and the regulation of the signals must be fully elucidated. Since opioid receptors are members of the G protein-coupled receptor (GPCR) superfamily, many of their signaling processes mimic those of other GPCRs. However, it is apparent from recent proteomic and other studies that opioid receptors, similar to several GPCRs in the rhodopsin subfamily, exist in signaling complexes. These signaling complexes include the oligomerization of the opioid receptors with each other, with other GPCRs, or with other cellular proteins, such as b-arrestin or regulators of G protein signaling (RGS) that could alter or modulate the final receptor signals. In addition, accumulating evidence points to the presence of an agonist-selective signaling process with the opioid receptors. In this chapter, we will review the classical signaling mechanisms of opioid receptors, the various effectors that are regulated by opioid receptors, and their possible roles in the in vivo functions of drugs, and cellular regulators that could influence the amplitude and duration of the signals. We will examine recent data that support the existence of opioid receptor signaling complexes, or "receptosomes," in the transduction of opioid receptor signals. Finally, evidence for ligand-selective signaling and its implication in future drug development will be discussed.

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“…On the other hand, heterologous desensitization involves G i -protein-independent kinases and is therefore not reversed with PTX (Pak et al, 1999) but by, for example, the tyrosine kinase inhibitor genistein (Pak et al, 1999) or the PKC inhibitor calphostin (Ueda et al, 2001). Hence, depending on the kinase primarily involved in receptor desensitization and internalization, PTX may antagonize the pro-apoptotic effects of morphine in some cells (Yin et al, 1997) but not in others (Maneckjee and Minna, 1992;Tegeder et al, 2003). These controversial findings therefore do not contradict the hypothesis of an "internalization/desensitization-dependent growth inhibition".…”

Section: Is Cell Death Initiated By Receptor Desensitizationmentioning

confidence: 99%

Opioids As Modulators of Cell Death and Survival—Unraveling Mechanisms and Revealing New Indications

2004

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Etorphine inhibits cell growth and induces apoptosis in SK-N-SH cells: involvement of pertussis toxin-sensitive G proteins

Cited by 54 publications

References 23 publications

Neuronal Apoptosis by Apolipoprotein E4 through Low-Density Lipoprotein Receptor-Related Protein and Heterotrimeric GTPases

Neuronal Apoptosis by Apolipoprotein E4 through Low-Density Lipoprotein Receptor-Related Protein and Heterotrimeric GTPases

Opioid Receptor Signal Transduction Mechanisms

Opioids As Modulators of Cell Death and Survival—Unraveling Mechanisms and Revealing New Indications

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