Caspase-3 activation as a bifurcation point between plasticity and cell death

Snigdha, Shikha; Smith, Erica D.; Prieto, G. Aleph; Cotman, Carl W.

doi:10.1007/s12264-012-1057-5

Cited by 206 publications

(153 citation statements)

References 75 publications

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“…The activation of caspase-3 has been identified in various types of cells observed with apoptosis (38). Caspase-3 was previously revealed as a downstream molecule of the Bcl-2 family (37).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑21 regulates the viability and apoptosis of diffuse large B‑cell lymphoma cells by upregulating B cell lymphoma‑2

Liu

Ruan

2017

Exp Ther Med

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Abstract. Diffuse large B-cell lymphoma (DLBCL), one of the most frequently diagnosed non-Hodgkin lymphoma (NHL), is partly attributed to hereditary factors. is an oncogenic substance that induces NHL and primarily targets tumor-suppressive molecules, such as B cell lymphoma-2 (Bcl-2). The present study explored whether Bcl-2, targeted by miR-21, would affect the development of NHL. Specimens were harvested from 55 patients with DLBCL who had undergone surgical treatment. Expression levels of miR-21 and Bcl-2 were evaluated through reverse transcription-quantitative polymerase chain reaction, immunohistochemistry and western blotting. Luciferase-reporter assays were performed to investigate the potential association between miR-21 and Bcl-2. MTT assays, flow cytometric analysis and caspase-3 activity assays were used to evaluate cell viability and apoptosis of DLBCL cells, respectively. Furthermore, statistical analysis was conducted using SPSS 19.0 software and the expression levels of miR-21 and Bcl-2 within DLBCL tissues were significantly upregulated when compared to those in normal tissues (P<0.01). As predicted by TargetScan, perfect base pairing was observed between the seed sequence of mature miR-21 and the 3' untranslated region of Bcl-2 mRNA. Dual luciferase reporter gene assays also revealed that miR-21 significantly facilitated the luciferase activity of Bcl-2 wild-type, with 61% upregulation (P<0.01) observed. MTT assays demonstrated that the viability of OCI-LY3 cells was decreased when cells were transfected with miR-21 inhibitor or Bcl-2 small interfering RNA and compared with those of control and negative control groups (all P<0.05). The apoptosis rate and caspase-3 activity level of the miR-21 group were 2.73±0.48 and 0.47±0.05, respectively, which were both significantly different from the groups with lower levels of miR-21 expression levels (all P<0.01). Since miR-21 may contribute to increased viability and decreased apoptosis of DLBCL cells through targeting Bcl-2, both Bcl-2 and miR-21 are likely to serve as effective targets for developing novel DLBCL treatments in the future.

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Section: Discussionmentioning

confidence: 99%

MicroRNA‑21 regulates the viability and apoptosis of diffuse large B‑cell lymphoma cells by upregulating B cell lymphoma‑2

Liu

Ruan

2017

Exp Ther Med

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“…Activation of caspase-3 is a key and common event of two major apoptosis signaling pathways, mitochondrial pathway and death receptor pathway (Mazumder et al, 2008;Snigdha et al, 2012). The death receptor pathway activates initiator caspase-8 and then cleaves its downstream effector caspases, such as caspase-3 which transducts the apoptosis signal, while the mitochondrial pathway is initiated by the mitochondrial dysfunction and then causes activation of caspase-9 which triggers caspase-3 activation (Fulda et al, 2006).…”

Section: Knockdown Of Med19 Enhances Chemo-sensitivity To Cisplamentioning

confidence: 99%

Knockdown of Med19 Suppresses Proliferation and Enhances Chemo-sensitivity to Cisplatin in Non-small Cell Lung Cancer Cells

Wei¹,

Wang²,

Sun³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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“…Caspase-3 (CASP3), which we find in this study to be decreased in synaptosomal fractions of morphine treated animals, is best known for its role during apoptosis as an executioner caspase that leads to neuronal cell death (58,59). However, recent studies have revealed not only developmental functions but also a functional role for this enzyme in the regulation of synaptic plasticity, learning, and memory (60). Studies have demonstrated the presence of caspase-3 in both dendrites and PSD fractions (61), and have shown that it can modulate synaptic transmission by interacting with and cleaving specific AMPA subunits at the PSD (62), and by regulating the internalization of synaptic AMPA receptors (63).…”

Section: Discussionmentioning

confidence: 58%

Morphine Regulated Synaptic Networks Revealed by Integrated Proteomics and Network Analysis

Stockton¹,

Gomes²,

Liu³

et al. 2015

Molecular & Cellular Proteomics

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Despite its efficacy, the use of morphine for the treatment of chronic pain remains limited because of the rapid development of tolerance, dependence and ultimately addiction. These undesired effects are thought to be because of alterations in synaptic transmission and neuroplasticity within the reward circuitry including the striatum. In this study we used subcellular fractionation and quantitative proteomics combined with computational approaches to investigate the morphine-induced protein profile changes at the striatal postsynaptic density. Over 2,600 proteins were identified by mass spectrometry analysis of subcellular fractions enriched in postsynaptic density associated proteins from saline or morphine-treated striata. Among these, the levels of 34 proteins were differentially altered in response to morphine. These include proteins involved in G-protein coupled receptor signaling, regulation of transcription and translation, chaperones, and protein degradation pathways. The altered expression levels of several of these proteins was validated by Western blotting analysis. Using Genes2Fans software suite we connected the differentially expressed proteins with proteins identified within the known background protein-protein interaction network. This led to the generation of a network consisting of 116 proteins with 40 significant intermediates. To validate this, we confirmed the presence of three proteins predicted to be significant intermediates: caspase-3, receptor-interacting serine/threonine protein kinase 3 and NEDD4 (an E3-ubiquitin ligase identified as a neural precursor cell expressed developmentally down-regulated protein 4). Because this morphine-regulated network predicted alterations in proteasomal degradation, we examined the global ubiquitination state of postsynaptic density proteins and found it to be substantially altered. Together, these findings suggest a role for protein degradation and for the ubiquitin/proteasomal system in the etiology of opiate dependence and addiction. Morphine and other opiates are the drugs of choice for the treatment of both severe and chronic pain. However, the utility of these compounds in the clinical setting is limited because of the rapid development of tolerance, physical dependence and addiction. The underlying cellular and molecular alterations through which chronic opiate exposure results in the persistent behavioral phenomenon of addiction remain poorly understood. However, there is evidence suggesting that the molecular composition of synapses within the reward circuitry of the central nervous system, particularly in the striatum, may be significantly altered (1). Moreover, given the critical involvement of the striatum in translating emotional or rewarding stimuli into motivated behaviors, alterations in this region induced by morphine and other abused drugs could contribute significantly to the pathophysiological responses at the heart of addiction (2). Although the debate surrounding the molecular and cellular mechanisms by which repeated drug adminis...

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Caspase-3 activation as a bifurcation point between plasticity and cell death

Cited by 206 publications

References 75 publications

MicroRNA‑21 regulates the viability and apoptosis of diffuse large B‑cell lymphoma cells by upregulating B cell lymphoma‑2

MicroRNA‑21 regulates the viability and apoptosis of diffuse large B‑cell lymphoma cells by upregulating B cell lymphoma‑2

Knockdown of Med19 Suppresses Proliferation and Enhances Chemo-sensitivity to Cisplatin in Non-small Cell Lung Cancer Cells

Morphine Regulated Synaptic Networks Revealed by Integrated Proteomics and Network Analysis

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