Proteolytic events in cryonecrotic cell death: Proteolytic activation of endonuclease P23

Grdović, Nevena; Vidaković, Melita; Mihailović, Mirjana; Dinić, Svetlana; Uskoković, Aleksandra; Arambašić, Jelena; Poznanović, Goran

doi:10.1016/j.cryobiol.2010.01.005

Cited by 7 publications

(5 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We and others previously demonstrated that during apoptosis the nuclear envelope and matrix-associated protein Lamin B (68 kD) is cleaved by caspase-3 into a distinct fragment of 46 kD. However, Lamin B is not cleaved during necrosis [39–41]. We also demonstrated previously that during TNF-α/ActD-induced apoptosis, Topo I (100 kD) is cleaved by caspases into a signature 70 kD fragment.…”

Section: Resultsmentioning

confidence: 76%

Docosahexanoic acid antagonizes TNF-α-induced necroptosis by attenuating oxidative stress, ceramide production, lysosomal dysfunction, and autophagic features

et al. 2014

View full text Add to dashboard Cite

Objective It was previously reported that docosahexanoic acid (DHA) reduces TNF-α-induced necrosis in L929 cells. However, the mechanisms underlying this reduction have not been investigated. The present study was designed to investigate cellular and biochemical mechanisms underlying the attenuation of TNF-α-induced necroptosis by DHA in L929 cells. Methods L929 cells were pre-treated with DHA prior to exposure to TNF-α, zVAD, or Necrostatin-1 (Nec-1). Cell death and survival were assessed by MTT and caspase activity assays, and microscopic visualization. Reactive oxygen species (ROS) were measured by flow cytometry. C16- and C18-ceramide were measured by mass spectrometry. Lysosomal membrane permeabilization (LMP) was evaluated by fluorescence microscopy and flow cytometry using Acridine Orange. Cathepsin L activation was evaluated by immunoblotting and fluorescence microscopy. Autophagy was assessed by immunoblotting of LC3-II and Beclin. Results Exposure of L929 cells to TNF-α alone for 24 h induced necroptosis, as evidenced by inhibition of cell death by Nec-1, absence of caspase-3 activity and lamin B cleavage, and morphological analysis. DHA attenuated multiple biochemical events associated with TNF-α-induced necroptosis, including ROS generation, ceramide production, lysosomal dysfunction, cathepsin L activation, and autophagic features. DHA also attenuated zVAD-induced necroptosis but did not attenuate the enhanced apoptosis and necrosis induced by combination of TNF-α with Actinomycin D or zVAD, respectively, suggesting that its protective effects might be limited by the strength of the cell death insult induced by TNF-α. Conclusions DHA effectively attenuates TNF-α-induced necroptosis and autophagy, most likely via its ability to inhibit TNF-α-induced sphingolipid metabolism and oxidative stress. These results highlight the role of this Omega-3 fatty acid in antagonizing inflammatory cell death.

show abstract

Section: Resultsmentioning

confidence: 76%

Docosahexanoic acid antagonizes TNF-α-induced necroptosis by attenuating oxidative stress, ceramide production, lysosomal dysfunction, and autophagic features

et al. 2014

View full text Add to dashboard Cite

show abstract

“…31 At the time of cell death, mature CathD is present in the nucleus and is involved in regulating the proteolytic activation of endonuclease. 32 In tumors, part of CathD fragments (amino acids 27–44) can interact with an unknown receptor on the cell surface, to promote the mitosis of cancer cells and stimulate the growth of cancer cells. 33 , 34 , 35 , 36 , 37 , 38 These studies demonstrate that CathD has an important role in controlling cell transformation and differentiation.…”

Section: Discussionmentioning

confidence: 99%

Cathepsin D deficiency delays central nervous system myelination by inhibiting proteolipid protein trafficking from late endosome/lysosome to plasma membrane

et al. 2018

View full text Add to dashboard Cite

This study aimed to investigate the role of cathepsin D (CathD) in central nervous system (CNS) myelination and its possible mechanism. By using CathD knockout mice in conjunction with immunohistochemistry, immunocytochemistry and western blot assays, the myelination of the CNS and the development of oligodendrocyte lineage cells in vivo and in vitro were observed. Endocytosis assays, real-time-lapse experiments and total internal reflection fluorescence microscopy were used to demonstrate the location and movement of proteolipid protein in oligodendrocyte lineage cells. In addition, the relevant molecular mechanism was explored by immunoprecipitation. The increase in Fluoromyelin Green staining and proteolipid protein expression was not significant in the corpus callosum of CathD−/− mice at the age of P11, P14 and P24. Proteolipid protein expression was weak at each time point and was mostly accumulated around the nucleus. The number of oligodendrocyte lineage cells (olig2+) and mature oligodendrocytes (CC1+) significantly decreased between P14 and P24. In the oligodendrocyte precursor cell culture of CathD−/− mice, the morphology of myelin basic protein-positive mature oligodendrocytes was simple while oligodendrocyte precursor cells showed delayed differentiation into mature oligodendrocytes. Moreover, more proteolipid protein gathered in late endosomes/lysosomes (LEs/Ls) and fewer reached the plasma membrane. Immunohistochemistry and immunoelectron microscopy analysis showed that CathD, proteolipid protein and VAMP7 could bind with each other, whereas VAMP7 and proteolipid protein colocalized with CathD in late endosome/lysosome. The findings of this paper suggest that CathD may have an important role in the myelination of CNS, presumably by altering the trafficking of proteolipid protein.

show abstract

“…More recently, it has been shown that cath-D can also activate pro-caspase 8, initiating neutrophil apoptosis during the resolution of inflammation [69]. Interestingly, a recent report indicates the presence of mature cath-D in the nucleus during cell death [70], and it has been proposed that nuclear cath-D may mediate the proteolytic activation of endonuclease 23 during cryonecrotic cell death [71].…”

Section: Pro-apoptotic Characteristics Of Cath-dmentioning

confidence: 99%

Pathophysiological functions of cathepsin D: Targeting its catalytic activity versus its protein binding activity?

et al. 2010

View full text Add to dashboard Cite

The lysosomal aspartic protease cathepsin D (cath-D) is overexpressed and hyper-secreted by epithelial breast cancer cells. This protease is an independent marker of poor prognosis in breast cancer as it is correlated with the incidence of clinical metastasis. In normal cells, cath-D is localized in intracellular vesicles (lysosomes and endosomes). In cancer cells, overexpressed cath-D accumulates in cells, where it may affect their degradative capacities, and the pro-enzyme is hyper-secreted in the tumor micro-environment. In addition, during apoptosis, lysosomal cath-D is released into the cytosol, where it may interact with and/or cleave pro-apoptotic, anti-apoptotic, or nuclear proteins. Several studies have shown that cath-D affects various different steps in tumor progression and metastasis. Cath-D stimulates cancer cell growth in an autocrine manner, and also cath-D plays a crucial paracrine role in the tumor micro-environment by stimulating fibroblast outgrowth and tumor angiogenesis. A mutant D231N-cath-D, which is devoid of catalytic activity, remained mitogenic, indicating an additional action of cath-D by protein-protein interaction. Targeting cath-D in cancer may require the use of inhibitors of its catalytic activity, but also the development of new tools to inhibit its protein binding functions. Thus, elucidation of the mechanism of action of cath-D is crucial if an appropriate strategy is to be developed to target this protease in cancer. The discovery of new physiological substrates of cath-D using proteomic approaches can be expected to generate new critical targets. The aim of this review is to describe the roles of the cath-D protease in cancer progression and metastasis, as well as its function in apoptosis, and to discuss how it can be targeted in cancer by inhibiting its proteolytic activity and/or its binding protein activity.

show abstract

Proteolytic events in cryonecrotic cell death: Proteolytic activation of endonuclease P23

Cited by 7 publications

References 56 publications

Docosahexanoic acid antagonizes TNF-α-induced necroptosis by attenuating oxidative stress, ceramide production, lysosomal dysfunction, and autophagic features

Docosahexanoic acid antagonizes TNF-α-induced necroptosis by attenuating oxidative stress, ceramide production, lysosomal dysfunction, and autophagic features

Cathepsin D deficiency delays central nervous system myelination by inhibiting proteolipid protein trafficking from late endosome/lysosome to plasma membrane

Pathophysiological functions of cathepsin D: Targeting its catalytic activity versus its protein binding activity?

Contact Info

Product

Resources

About