Steroid regulation of autophagic programmed cell death during development

Apoptosis and autophagy are morphologically distinct forms of programmed cell death. While autophagy occurs during the development of diverse organisms and has been implicated in tumorigenesis, little is known about the molecular mechanisms that regulate this type of cell death. Here we show that steroid-activated programmed cell death of Drosophila salivary glands occurs by autophagy. Expression of p35 prevents DNA fragmentation and partially inhibits changes in the cytosol and plasma membranes of dying salivary glands, suggesting that caspases are involved in autophagy. The steroid-regulated BR-C, E74A and E93 genes are required for salivary gland cell death. BR-C and E74A mutant salivary glands exhibit vacuole and plasma membrane breakdown, but E93 mutant salivary glands fail to exhibit these changes, indicating that E93 regulates early autophagic events. Expression of E93 in embryos is sufficient to induce cell death with many characteristics of apoptosis, but requires the H99 genetic interval that contains the rpr, hid and grim proapoptotic genes to induce nuclear changes diagnostic of apoptosis. In contrast, E93 expression is sufficient to induce the removal of cells by phagocytes in the absence of the H99 genes. These studies indicate that apoptosis and autophagy utilize some common regulatory mechanisms.

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Steroid regulated programmed cell death during Drosophila metamorphosis

Development ◽

10.1242/dev.124.22.4673 ◽

1997 ◽

Vol 124 (22) ◽

pp. 4673-4683 ◽

Cited By ~ 12

Author(s):

C. Jiang ◽

E.H. Baehrecke ◽

C.S. Thummel

Keyword(s):

Cell Death ◽

Salivary Gland ◽

Programmed Cell Death ◽

Salivary Glands ◽

Ectopic Expression ◽

Salivary Gland Cell ◽

Cell Nuclei ◽

Larval Midgut ◽

Insect Metamorphosis ◽

Specific Regulation

During insect metamorphosis, pulses of the steroid hormone 20-hydroxyecdysone (ecdysone) direct the destruction of obsolete larval tissues and their replacement by tissues and structures that form the adult fly. We show here that larval midgut and salivary gland histolysis are stage-specific steroid-triggered programmed cell death responses. Dying larval midgut and salivary gland cell nuclei become permeable to the vital dye acridine orange and their DNA undergoes fragmentation, indicative of apoptosis. Furthermore, the histolysis of these tissues can be inhibited by ectopic expression of the baculovirus anti-apoptotic protein p35, implicating a role for caspases in the death response. Coordinate stage-specific induction of the Drosophila death genes reaper (rpr) and head involution defective (hid) immediately precedes the destruction of the larval midgut and salivary gland. In addition, the diap2 anti-cell death gene is repressed in larval salivary glands as rpr and hid are induced, suggesting that the death of this tissue is under both positive and negative regulation. Finally, diap2 is repressed by ecdysone in cultured salivary glands under the same conditions that induce rpr expression and trigger programmed cell death. These studies indicate that ecdysone directs the death of larval tissues via the precise stage- and tissue-specific regulation of key death effector genes.

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Iron Starvation and Culture Age Activate Metacaspases and Programmed Cell Death in the Marine Diatom Thalassiosira pseudonana

Eukaryotic Cell ◽

10.1128/ec.00296-07 ◽

2007 ◽

Vol 7 (2) ◽

pp. 223-236 ◽

Cited By ~ 77

Author(s):

Kay D. Bidle ◽

Sara J. Bender

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Plasma Membranes ◽

Molecular Mechanisms ◽

Short Circuit ◽

Thalassiosira Pseudonana ◽

Marine Diatom ◽

Molecular Evidence ◽

Iron Starvation ◽

Gene And Protein Expression

ABSTRACT In the modern ocean, phytoplankton maintain extremely high primary production/biomass ratios, indicating that they bloom, die, and are replaced weekly. The molecular mechanisms regulating cellular mortality and turnover are largely unknown, even though they effectively short-circuit carbon export to the deep ocean and channel primary productivity to microbial food webs. Here, we present morphological, biochemical, and molecular evidence of caspase-mediated, autocatalytic programmed cell death (PCD) in the diatom Thalassiosira pseudonana in response to iron starvation. Transmission electron microscopy revealed internal degradation of nuclear, chloroplastic, and mitochondrial organelles, all while the plasma membranes remained intact. Cellular degradation was concomitant with dramatic decreases in photosynthetic efficiency, externalization of phosphatidylserine, and significantly elevated caspase-specific activity, with the addition of a broad-spectrum caspase inhibitor rescuing cells from death. A search of the T. pseudonana genome identified six distinct putative metacaspases containing a conserved caspase domain structure. Quantitative reverse transcription-PCR and Western blot analysis revealed differential gene and protein expression of T. pseudonana metacaspases, some of which correlated with physiological stress and caspase activity. Taken together with the recent discovery of the metacaspase-mediated viral infection of phytoplankton (K. D. Bidle, L. Haramaty, J. Barcelos-Ramos, and P. G. Falkowski, Proc. Natl. Acad. Sci. USA 104:6049-6054, 2007), our findings reveal a key role for metacaspases in the turnover of phytoplankton biomass in the oceans. Furthermore, given that Fe is required for photosynthetic electron transfer and is chronically limiting in a variety of oceanic systems, including high-nutrient low-chlorophyll regions, our findings provide a potential ecological context for PCD in these unicellular photoautotrophs.

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Down-regulation of inhibitor of apoptosis levels provides competence for steroid-triggered cell death

The Journal of Cell Biology ◽

10.1083/jcb.200703206 ◽

2007 ◽

Vol 178 (1) ◽

pp. 85-92 ◽

Cited By ~ 32

Author(s):

Viravuth P. Yin ◽

Carl S. Thummel ◽

Arash Bashirullah

Keyword(s):

Cell Death ◽

Salivary Gland ◽

Salivary Glands ◽

Gland Cell ◽

Inhibitor Of Apoptosis ◽

Salivary Gland Cell ◽

Creb Binding Protein ◽

Down Regulation ◽

Steroid Signaling ◽

Necessary And Sufficient

A pulse of the steroid hormone ecdysone triggers the destruction of larval salivary glands during Drosophila metamorphosis through a transcriptional cascade that converges on reaper (rpr) and head involution defective (hid) induction, resulting in caspase activation and cell death. We identify the CREB binding protein (CBP) transcriptional cofactor as essential for salivary gland cell death. We show that CBP acts 1 d before the onset of metamorphosis in apparent response to a mid-third instar ecdysone pulse, when CBP is necessary and sufficient for down-regulation of the Drosophila inhibitor of apoptosis 1 (DIAP1). It is only after DIAP1 levels are reduced that salivary glands become competent to die through rpr/hid-mediated cell death. Before this time, high levels of DIAP1 block salivary gland cell death, even in the presence of ectopic rpr expression. This study shows that naturally occurring changes in inhibitor of apoptosis levels can be critical for regulating cell death during development. It also provides a molecular mechanism for the acquisition of competence in steroid signaling pathways.

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Progress in understanding the role of lncRNA in programmed cell death

Cell Death Discovery ◽

10.1038/s41420-021-00407-1 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Na Jiang ◽

Xiaoyu Zhang ◽

Xuejun Gu ◽

Xiaozhuang Li ◽

Lei Shang

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Molecular Mechanisms ◽

Membrane Receptors ◽

Gene Expressions ◽

Apoptosis Pathway ◽

Stem Cell Pluripotency ◽

Extrinsic Apoptosis ◽

Related Proteins ◽

Cycle Regulation

AbstractLong non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides but not translated into proteins. LncRNAs regulate gene expressions at multiple levels, such as chromatin, transcription, and post-transcription. Further, lncRNAs participate in various biological processes such as cell differentiation, cell cycle regulation, and maintenance of stem cell pluripotency. We have previously reported that lncRNAs are closely related to programmed cell death (PCD), which includes apoptosis, autophagy, necroptosis, and ferroptosis. Overexpression of lncRNA can suppress the extrinsic apoptosis pathway by downregulating of membrane receptors and protect tumor cells by inhibiting the expression of necroptosis-related proteins. Some lncRNAs can also act as competitive endogenous RNA to prevent oxidation, thereby inhibiting ferroptosis, while some are known to activate autophagy. The relationship between lncRNA and PCD has promising implications in clinical research, and reports have highlighted this relationship in various cancers such as non-small cell lung cancer and gastric cancer. This review systematically summarizes the advances in the understanding of the molecular mechanisms through which lncRNAs impact PCD.

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Molecular basis of disregulation of programmed lymphocytes’ death in chronic viral infection

Bulletin of Siberian Medicine ◽

10.20538/1682-0363-2006-2-23-34 ◽

2006 ◽

Vol 5 (2) ◽

pp. 23-34

Author(s):

V. V. Novitsky ◽

N. V. Ryazantseva ◽

O. B. Zhoukova

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Viral Infection ◽

Immune Cells ◽

Molecular Basis ◽

Molecular Mechanisms ◽

Recent Literature ◽

Chronic Viral Infection ◽

Persistent Viruses

The review analyses information from recent literature and results of the authors’ own investigations concerning imbalance of programmed cell death in forming chronic viral infection. Molecular mechanisms of apoptosis modulation of immune cells by persistent viruses are discussed in the article.

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Mutations in the Parkinson’s Disease-Associated PARK2 Gene Are Accompanied by Imbalance in Programmed Cell Death Systems

Acta Naturae ◽

10.32607/20758251-2015-7-4-146-149 ◽

2015 ◽

Vol 7 (4) ◽

pp. 146-149 ◽

Cited By ~ 8

Author(s):

E. V. Konovalova ◽

O. M. Lopacheva ◽

I. A. Grivennikov ◽

O. S. Lebedeva ◽

E. В. Dashinimaev ◽

...

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Dopaminergic Neurons ◽

Molecular Mechanisms ◽

Disease Patient ◽

Parkinsons Disease ◽

Leading Role ◽

Midbrain Dopaminergic Neurons ◽

Induced Pluripotent ◽

Apoptotic Factors

Parkinsons disease is caused by the degeneration of midbrain dopaminergic neurons. A rare recessive form of the disease may be caused by a mutation in the PARK2 gene, whose product, Parkin, controls mitophagy and programmed cell death. The level of pro- and anti-apoptotic factors of the Bcl-2 family was determined in dopaminergic neurons derived from the induced pluripotent stem cells of a healthy donor and a Parkinsons disease patient bearing PARK2 mutations. Western blotting was used to study the ratios of Bax, Bak, Bcl-2, Bcl-XL, and Bcl-W proteins. The pro-apoptotic Bak protein level in PARK2-neurons was shown to be two times lower than that in healthy cells. In contrast, the expression of the anti-apoptotic factors Bcl-XL, Bcl-W, and Bcl-2 was statistically significantly higher in the mutant cells compared to healthy dopaminergic neurons. These results indicate that PARK2 mutations are accompanied by an imbalance in programmed cell death systems in which non-apoptotic molecular mechanisms play the leading role.

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The nitrogen-fixing symbiotic cyanobacterium, Nostoc punctiforme can regulate plant programmed cell death

10.1101/2020.08.13.249318 ◽

2020 ◽

Author(s):

Samuel P. Belton ◽

Paul F. McCabe ◽

Carl K. Y. Ng

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Molecular Mechanisms ◽

Differential Regulation ◽

Nitrogen Fixing ◽

Nostoc Punctiforme ◽

Transcriptional Reprogramming ◽

Cell Growth And Differentiation ◽

Transcriptome Resource ◽

Developmental Signalling

AbstractCyanobacteria such as Nostoc spp. can form nitrogen-fixing symbioses with a broad range of plant species. Unlike other plant-bacteria symbioses, little is understood about the immunological and developmental signalling events induced by Nostoc cyanobionts (symbiotic cyanobacteria). Here, we used suspension cell cultures to elucidate the early molecular mechanisms underpinning the association between cyanobionts and plants by studying the effects of conditioned medium (CM) from Nostoc punctiforme cultures on plant programmed cell death (PCD), a typical immune response activated during incompatible interactions. We showed that N. punctiforme-CM could suppress PCD induced by a temperature stress. Interestingly, this was preceded by significant transcriptional reprogramming, as evidenced by the differential regulation of a network of defence-associated genes, as well as genes implicated in regulating cell growth and differentiation. This work is the first to show that cyanobionts can regulate PCD in plants and provides a valuable transcriptome resource for the early immunological and developmental signalling events elicited by Nostoc cyanobionts.

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Programmed Cell Death: Molecular Mechanisms and Implications for Safety Assessment of Nanomaterials

Accounts of Chemical Research ◽

10.1021/ar300020b ◽

2012 ◽

Vol 46 (3) ◽

pp. 733-742 ◽

Cited By ~ 133

Author(s):

Fernando Torres Andón ◽

Bengt Fadeel

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Safety Assessment ◽

Molecular Mechanisms

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Long-term depression: a cell biological view

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2013.0138 ◽

2014 ◽

Vol 369 (1633) ◽

pp. 20130138 ◽

Cited By ~ 23

Author(s):

Morgan Sheng ◽

Ali Ertürk

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Dendritic Spines ◽

Crucial Role ◽

Molecular Mechanisms ◽

Signalling Pathways ◽

Long Term Depression ◽

A Cell ◽

Biological Programme

Recent studies of the molecular mechanisms of long-term depression (LTD) suggest a crucial role for the signalling pathways of apoptosis (programmed cell death) in the weakening and elimination of synapses and dendritic spines. With this backdrop, we suggest that LTD can be considered as the electrophysiological aspect of a larger cell biological programme of synapse involution, which uses localized apoptotic mechanisms to sculpt synapses and circuits without causing cell death.

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