Nerve growth factor-mediated inhibition of apoptosis post-caspase activation is due to removal of active caspase-3 in a lysosome-dependent manner

Mnich, Katarzyna; Carleton, Laura A.; Kavanagh, Edel; Doyle, Karen M.; Samali, Afshin; Gorman, Adrienne M.

doi:10.1038/cddis.2014.173

Cited by 41 publications

(20 citation statements)

References 59 publications

(83 reference statements)

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“…Thus, autophagy-based cancer clinical trials should select autophagy inhibitors or activators that can induce apoptosis or autophagic cell death contingent upon different tumor contexts. It has been acknowledged that autophagy endows established cancer with survival advantages partly via degradation of pro-apoptotic proteins such as caspase3 [ 127 ], caspase8 [ 169 ] and PUMA [ 51 ]. Therefore, chloroquine (CQ) and bafilomycinA1 as lysosomal acidification inhibitors may execute their anti-tumor function by potentiating apoptosis [ 170 , 171 ].…”

Section: Protein Degradation: Therapeutic Opportunitiesmentioning

confidence: 99%

The different roles of selective autophagic protein degradation in mammalian cells

et al. 2015

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Autophagy is an intracellular pathway for bulk protein degradation and the removal of damaged organelles by lysosomes. Autophagy was previously thought to be unselective; however, studies have increasingly confirmed that autophagy-mediated protein degradation is highly regulated. Abnormal autophagic protein degradation has been associated with multiple human diseases such as cancer, neurological disability and cardiovascular disease; therefore, further elucidation of protein degradation by autophagy may be beneficial for protein-based clinical therapies. Macroautophagy and chaperone-mediated autophagy (CMA) can both participate in selective protein degradation in mammalian cells, but the process is quite different in each case. Here, we summarize the various types of macroautophagy and CMA involved in determining protein degradation. For this summary, we divide the autophagic protein degradation pathways into four categories: the post-translational modification dependent and independent CMA pathways and the ubiquitin dependent and independent macroautophagy pathways, and describe how some non-canonical pathways and modifications such as phosphorylation, acetylation and arginylation can influence protein degradation by the autophagy lysosome system (ALS). Finally, we comment on why autophagy can serve as either diagnostics or therapeutic targets in different human diseases.

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Section: Protein Degradation: Therapeutic Opportunitiesmentioning

confidence: 99%

The different roles of selective autophagic protein degradation in mammalian cells

et al. 2015

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“…Bcl2 blocks and Bax induces the release of apoptogenic factors, which in turn stimulate initiator caspases, leading to the activation of the executioner caspase-3 [45]. The activation of the caspase-3 protease leads to the formation of cleaved caspase-3, which constitutes a vital step in the apoptotic process by inducing DNA degradation or fragmentation [46]. In the present study, treatment with venlafaxine significantly upregulated Bcl2 expression, downregulated Bax expression, and decreased the caspase-3 level in the hippocampus of OVX rats.…”

Section: Discussionmentioning

confidence: 99%

Venlafaxine Mitigates Depressive-Like Behavior in Ovariectomized Rats by Activating the EPO/EPOR/JAK2 Signaling Pathway and Increasing the Serum Estradiol Level

et al. 2019

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Reduced estradiol levels are associated with depression in women during the transition to and after menopause. A considerable number of studies focusing on the theme of treating depression through the activation of erythropoietin (EPO)-induced signaling pathways have been published. Venlafaxine is an approved antidepressant drug that inhibits both serotonin and norepinephrine transporters. The aim of the present study was to investigate the effects of venlafaxine on the depressive-like behaviors and serum estradiol levels in female rats following ovariectomy (OVX) and the possible roles of EPO-induced signaling pathways. Venlafaxine (10 mg/kg/day) was orally administered to OVX rats over a period of 4 weeks using two different treatment regimens: either starting 24 h or 2 weeks after OVX. Venlafaxine showed a superior efficacy in inducing antidepressant-like effects after an acute treatment (24 h post-OVX) than after the delayed treatment (2 weeks post-OVX) and was characterized by a decreased immobility time in the forced swimming test. In parallel, venlafaxine induced EPO and EPO receptor mRNA expression and increased levels of phospho-Janus kinase 2 (p-JAK2), phospho-signal transducer and activator of transcription 5, and phosphoextracellular signal-regulated kinase 1/2 in the hippocampus of OVX rats. Meanwhile, rats exhibited a marked reduction in the hippocampal Bax/Bcl2 ratio, caspase-3 activity, and tumor necrosis factor alpha levels after venlafaxine treatment. Venlafaxine also increased the hippocampal brain-derived neurotrophic factor and serum estradiol levels. Based on these findings, venlafaxine exerts a neuroprotective effect on OVX rats that is at least partially attributed to the activation of EPO/EPOR/JAK2 signaling pathways, anti-apoptotic activities, anti-inflammatory activities, and neurotrophic activities, as well as an increase in serum estradiol level.

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“…Thus, the reduced release of cytochrome c further alleviates the activation of BAX. Upon MOMP, cytochrome c translocates into the cytosol to initiate formation of the apoptosome complex, leading to proximity-induced auto-activation of initiator caspase-9 and, once activated, caspase-9 cleaves and activates executioner caspases, such as caspase-3 and -7 60 . Caspase-3 is a predominant effector caspase in apoptosis 59 .…”

Section: Discussionmentioning

confidence: 99%

Sodium tanshinone IIA sulfonate protects ARPE-19 cells against oxidative stress by inhibiting autophagy and apoptosis

Han

Liu

et al. 2018

Sci Rep

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Oxidative stress in retinal pigment epithelium (RPE) is considered to be a major contributor to the development and progression of age-related macular degeneration (AMD). Previous investigations have shown that sodium tanshinone IIA sulfonate (STS) can alleviate oxidative stress in haemorrhagic shock-induced organ damage and cigarette smoke-induced chronic obstructive pulmonary disease in mice. However, whether STS has a protective effect in ARPE-19 cells under oxidative stress and its exact mechanisms have not yet been fully elucidated. In the present study, we utilized H2O2 to establish an oxidative stress environment. Our findings show that STS activated the PI3K/AKT/mTOR pathway to inhibit autophagy and diminished the expression of the autophagic proteins Beclin 1, ATG3, ATG7 and ATG9 in ARPE-19 cells under oxidative stress. Detection of the intrinsic apoptosis-related factors BAX, mitochondrial membrane potential (MMP), caspase-9, caspase-3 and BCL-2, as well as the extrinsic apoptosis-related factors c-FLIP, v-FLIP and caspase-8, confirmed that STS inhibited the intrinsic and extrinsic apoptotic pathways, and attenuated apoptosis in ARPE-19 cells under oxidative stress conditions. These findings shed new light on the protective effects of STS in ARPE-19 cells and its mechanisms under oxidative stress to provide novel and promising therapeutic strategies for AMD.

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Nerve growth factor-mediated inhibition of apoptosis post-caspase activation is due to removal of active caspase-3 in a lysosome-dependent manner

Cited by 41 publications

References 59 publications

The different roles of selective autophagic protein degradation in mammalian cells

The different roles of selective autophagic protein degradation in mammalian cells

Venlafaxine Mitigates Depressive-Like Behavior in Ovariectomized Rats by Activating the EPO/EPOR/JAK2 Signaling Pathway and Increasing the Serum Estradiol Level

Sodium tanshinone IIA sulfonate protects ARPE-19 cells against oxidative stress by inhibiting autophagy and apoptosis

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