scholarly journals Stachyose triggers apoptotic like cell death in drought sensitive but not resilient plants

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Pauline Okemo ◽  
Hao Long ◽  
Yen Cheng ◽  
Sagadevan Mundree ◽  
Brett Williams
Keyword(s):  
Cell Death ◽  
Stress Tolerance ◽  
Metabolic Pathways ◽  
Large Scale ◽  
Plant Defence ◽  
Sugar Metabolism ◽  
Potential Candidate ◽  
Induction Of Apoptosis ◽  
Stachyose Synthase

AbstractProgrammed cell death (PCD) is one of the most intensively researched fields in modern mammalian biology with roles in cancer, aging, diabetes and numerous neurodegenerative diseases. It is becoming increasingly clear that PCD also plays significant roles in plant defence and responses to the environment. Given their unique ability to tolerate desiccation (cells remain viable even after they’ve lost 95% of their water), resurrection plants make ideal models to study the regulation of plant PCD pathways. Previously, we showed that the Australian resurrection plant, Tripogon loliiformis, suppresses plant PCD, via trehalose-mediated activation of autophagy pathways, during drying. In the present study, we created a full-length T. loliiformis cDNA library, performed a large-scale Agrobacterium screen for improved salinity tolerance and identified Stachyose synthase (TlStach) as a potential candidate for improving stress tolerance. Tripogon loliiformis shoots accumulate stachyose synthase transcripts and stachyose during drying. Attempts to generate transgenic plants expressing TlStach failed and were consistent with previous reports in mammals that demonstrated stachyose-mediated induction of apoptosis. Using a combination of transcriptomics, metabolomics and cell death assays (TUNNEL and DNA laddering), we investigated whether stachyose induces apoptotic-like cell death in T. loliiformis. We show that stachyose triggers the formation of the hallmarks of plant apoptotic-like cell death in the desiccation sensitive Nicotiana benthamiana but not the resilient T. loliiformis. These findings suggest that T. loliiformis suppresses stachyose-mediated apoptotic-like cell death and provides insights on the role of sugar metabolism and plant PCD pathways. A better understanding of how resilient plants regulate sugar metabolism and PCD pathways may facilitate future targeting of plant metabolic pathways for increased stress tolerance.

scholarly journals Ferroptosis in plants: triggers, proposed mechanisms, and the role of iron in modulating cell death

2020 ◽  
Author(s):  
Ayelén Mariana Distéfano ◽  
Gabriel Alejandro López ◽  
Nicolás Setzes ◽  
Fernanda Marchetti ◽  
Maximiliano Cainzos ◽  
...  
Keyword(s):  
Cell Death ◽  
Metabolic Pathways ◽  
Oxygen Species ◽  
Cell Death Pathway ◽  
Plant Life ◽  
Regulated Cell Death ◽  
Dependent Cell ◽  
Plant Life Cycle ◽  
High Degree

Abstract Regulated cell death plays key roles during essential processes throughout the plant life cycle. It takes part in specific developmental programs and maintains homeostasis of the organism in response to unfavorable environments. Ferroptosis is a recently discovered iron-dependent cell death pathway characterized by the accumulation of lipid reactive oxygen species. In plants, ferroptosis shares all the main hallmarks described in other systems. Those specific features include biochemical and morphological signatures that seem to be conserved among species. However, plant cells have specific metabolic pathways and a high degree of metabolic compartmentalization. Together with their particular morphology, these features add more complexity to the plant ferroptosis pathway. In this review, we summarize the most recent advances in elucidating the roles of ferroptosis in plants, focusing on specific triggers, the main players, and underlying pathways.

scholarly journals Activation of SAT1 engages polyamine metabolism with p53-mediated ferroptotic responses

2016 ◽  
Vol 113 (44) ◽  
pp. E6806-E6812 ◽  
Author(s):  
Yang Ou ◽  
Shang-Jui Wang ◽  
Dawei Li ◽  
Bo Chu ◽  
Wei Gu
Keyword(s):  
Cell Death ◽  
Metabolic Pathways ◽  
Cell Metabolism ◽  
Specific Inhibitor ◽  
Polyamine Metabolism ◽  
Cycle Arrest ◽  
Induced Stress ◽  
Rate Limiting ◽  
Insight Into

Although p53-mediated cell-cycle arrest, senescence, and apoptosis remain critical barriers to cancer development, the emerging role of p53 in cell metabolism, oxidative responses, and ferroptotic cell death has been a topic of great interest. Nevertheless, it is unclear how p53 orchestrates its activities in multiple metabolic pathways into tumor suppressive effects. Here, we identified the SAT1 (spermidine/spermine N1-acetyltransferase 1) gene as a transcription target of p53. SAT1 is a rate-limiting enzyme in polyamine catabolism critically involved in the conversion of spermidine and spermine back to putrescine. Surprisingly, we found that activation of SAT1 expression induces lipid peroxidation and sensitizes cells to undergo ferroptosis upon reactive oxygen species (ROS)-induced stress, which also leads to suppression of tumor growth in xenograft tumor models. Notably, SAT1 expression is down-regulated in human tumors, and CRISPR-cas9–mediated knockout of SAT1 expression partially abrogates p53-mediated ferroptosis. Moreover, SAT1 induction is correlated with the expression levels of arachidonate 15-lipoxygenase (ALOX15), and SAT1-induced ferroptosis is significantly abrogated in the presence of PD146176, a specific inhibitor of ALOX15. Thus, our findings uncover a metabolic target of p53 involved in ferroptotic cell death and provide insight into the regulation of polyamine metabolism and ferroptosis-mediated tumor suppression.

scholarly journals Antidepressant Sertraline Hydrochloride Inhibits the Growth of HER2+ AU565 Breast Cancer Cell Line through Induction of Apoptosis, and Arrest of Cell Cycle

2021 ◽  
Author(s):  
Atia-tul- Wahab ◽  
Sharmeen Fayyaz ◽  
Rimsha Irshad ◽  
Rafat A. Siddiqui ◽  
Atta-ur- Rahman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Cell Line ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Caspase 3 ◽  
Potential Candidate ◽  
Sertraline Hydrochloride ◽  
Induction Of Apoptosis

AbstractBreast cancer is one the most aggressive cancer worldwide, especially Pakistan due to limited therapeutic options. This study was conducted to repurpose the use of selective serotonin reuptake inhibitors (SSRIs), in the treatment of breast cancers, and merit to pursue drug re-positioning in oncology. Anti-proliferative activity of SSRIs, such as fluoxetine, paroxetine, and sertraline hydrochloride on the growth of AU-565, MCF-7, MDA-MB-231, and BT-474 breast cancer cell lines, along with human fibroblast BJ cells was determined in vitro. Changes in nuclear morphology (DAPI staining), and induction of apoptosis (flow cytometry, and caspase-3 activation) were also studied. Sertraline hydrochloride most effectively inhibited the growth of breast cancer cells in vitro. Therefore, pharmacological mechanism involved in sertraline mediated cell death was investigated in HER2+ AU565 cell line. Enhanced nuclear fragmentation, increased Annexin (+) cells, and caspase-3/7 activation indicated that sertraline-mediated cell death could be a result of BCl2-independent apoptosis as evidenced by expression of Bax, and BCl2 genes. Taken together, our results identified sertraline hydrochloride, as a potential candidate for the treatment of HER2-positive breast cancer. Even though these are in vitro results, this study opens great opportunity in the field of drug repurposing for the development of chemotherapeutic agents.

Complementary transcriptome and proteome analyses provide insight into floral transition in Bamboo (Dendrocalamus latiflorus Munro)

2020 ◽  
Author(s):  
Xiaoyan Wang ◽  
Yujiao Wang ◽  
Guoqian Yang ◽  
Lei Zhao ◽  
Dezhu Li ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Large Scale ◽  
De Novo ◽  
Sugar Metabolism ◽  
Floral Transition ◽  
Growth Phases ◽  
Vegetable Growth ◽  
Plant Maturity ◽  
Woody Bamboos ◽  
Insight Into

Abstract Background Most woody bamboos flower only once after long vegetable growth phases and die immediately afterward. It is difficult to know the timing of the floral transition, as little information is available on the molecular mechanism of plant maturity in bamboos. Results In this study, through RNA sequencing of leaves of D. latiflorus during floral transition and de novo assembly, a final set of 155,494 unigenes were obtained with N50 of 2,069 bp. We identified a lot of flowering time-associated and flowering integration genes and the continued increase and decrease genes were screened as flowering biomarker genes, such as MADS14, bHLH13, ABA-related genes. The different genes were assigned to specific metabolic pathways by Kyoto Encyclopedia of Genes and Genomes (KEGG) and the photoperiod pathways depending on the circadian rhythm may play an essential role in the bamboo floral transition. In addition, a total of 721 different expressed proteins of leaves from the vegetable-to-reproductive stages in the same flowering clumps were identified using iTRAQ technique. The correlations between the expression levels of a transcript and the abundance of its corresponding protein were observed infrequently, but the very strong correlation in the specific metabolic process was observed, such as carbon metabolism, sugar metabolism, and photosynthesis, underlining the importance of these metabolic pathways during floral transition. Conclusions In this report, we combined transcriptome with large-scale quantitative proteomes to investigate the flower transition of D. latiflorus. This work will provide insights into mechanism of floral transition for bamboos, and management of forest breeding.

scholarly journals Microscopic Photosensitization: A New Tool to Investigate the Role of Mitochondria in Cell Death

2002 ◽  
Vol 2 ◽  
pp. 1198-1208 ◽  
Author(s):  
May-Ghee Lum ◽  
Tetsuhiro Minamikawa ◽  
Phillip Nagley
Keyword(s):  
Cell Death ◽  
Laser Irradiation ◽  
Laser Scanning ◽  
Annexin V ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Rapid Loss ◽  
Active Involvement ◽  
Induction Of Apoptosis

Active involvement of mitochondria in cell death has been well-documented, but local apoptotic signaling between subsets of mitochondria has been poorly explored to date. Using mitochondrially localized CMXRos as a photosensitizer coupled to laser irradiation by confocal laser scanning microscopy, we demonstrate that partial irradiation of about half the mitochondria in human 143B TK–cells induces rapid loss of mitochondrial membrane potential (ΔΨm) in nonirradiated mitochondria. Cells so partially irradiated show apoptotic indications, including mobilization of cytochrome c and binding of annexin V within 2 h following irradiation. The loss of ΔΨm in nonirradiated mitochondria did not occur in cells photoirradiated in the absence of CMXRos. Increasing the proportion of irradiated mitochondria in each cell (up to about 50%) generated a correspondingly greater percentage of cells in which nonirradiated mitochondria lost ΔΨm and which also showed apoptotic indications. Only at the highest level of irradiation (global for all mitochondria in one cell) were signs of necrosis evident (judged by uptake of propidium iodide). Because laser irradiation is specific to the subpopulation of mitochondria targeted, the data imply that a signal emanating from irradiated mitochondria is processed by their nonirradiated counterparts. We conclude that intermitochondrial signaling occurs in the subcellular response to induction of apoptosis.

scholarly journals Regulation of Caspase-3 and Bcl-2 Expression in Dalton's Lymphoma Ascites Cells by Abrin

2009 ◽  
Vol 6 (2) ◽  
pp. 233-238 ◽  
Author(s):  
V. Ramnath ◽  
P. S. Rekha ◽  
G. Kuttan ◽  
R. Kuttan
Keyword(s):  
Cell Death ◽  
Caspase 3 ◽  
Morphological Changes ◽  
Suppressor Gene ◽  
Necrotic Cell ◽  
Induction Of Apoptosis ◽  
Dla Cells ◽  
Dalton’S Lymphoma ◽  
Dalton's Lymphoma

The role of abrin, a toxic lectin isolated from seeds ofAbrus precatoriusLinn in inducing apoptosis in murine Dalton's Lymphoma Ascites (DLA) cells was evaluated. Abrin when incubated at the concentration of 10 ng per million DLA cells could bring about cell death as typical morphological changes with apoptosis. However, necrotic cell death dominated when a higher dose of abrin was used. DNA samples, isolated from DLA cells treated with abrin showed fragmentation. Abrin brought about induction of apoptosis by stimulating the expression of pro-apoptotic Caspase-3, at the same time blocking the expression of Bcl-2, which is an anti apoptotic gene. However, the expression of tumor suppressor gene p53 has not been observed in control and abrin-treated DLA cells. Results suggested that abrin effectively induced apoptotic changes in the tumor cells that led to cellular death.

scholarly journals The Role of Phyto-Melatonin and Related Metabolites in Response to Stress

Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 1887 ◽  
Author(s):  
Yang Yu ◽  
Yan Lv ◽  
Yana Shi ◽  
Tao Li ◽  
Yanchun Chen ◽  
...  
Keyword(s):  
Stress Tolerance ◽  
Metabolic Pathways ◽  
Plant Stress ◽  
Stress Conditions ◽  
Photosynthesis Inhibition ◽  
Response To Stress ◽  
Plant Stress Tolerance ◽  
New Perspective ◽  
Catabolism Pathway

Plant hormone candidate melatonin has been widely studied in plants under various stress conditions, such as heat, cold, salt, drought, heavy metal, and pathogen attack. Under stress, melatonin usually accumulates sharply by modulating its biosynthesis and metabolic pathways. Beginning from the precursor tryptophan, four consecutive enzymes mediate the biosynthesis of tryptamine or 5-hydroxytryptophan, serotonin, N-acetylserotonin or 5-methoxytryptamine, and melatonin. Then, the compound is catabolized into 2-hydroxymelatonin, cyclic-3-hydroxymelatonin, and N1-acetyl-N2-formyl-5-methoxyknuramine through 2-oxoglutarate-dependent dioxygenase catalysis or reaction with reactive oxygen species. As an ancient and powerful antioxidant, melatonin directly scavenges ROS induced by various stress conditions. Furthermore, it confreres stress tolerance by activating the plant’s antioxidant system, alleviating photosynthesis inhibition, modulating transcription factors that are involved with stress resisting, and chelating and promoting the transport of heavy metals. Melatonin is even proven to defense against pathogen attacks for the plant by activating other stress-relevant hormones, like salicylic acid, ethylene, and jasmonic acid. Intriguingly, other precursors and metabolite molecules involved with melatonin also can increase stress tolerance for plant except for unconfirmed 5-methoxytryptamine, cyclic-3-hydroxymelatonin, and N1-acetyl-N2-formyl-5-methoxyknuramine. Therefore, the precursors and metabolites locating at the whole biosynthesis and catabolism pathway of melatonin could contribute to plant stress resistance, thus providing a new perspective for promoting plant stress tolerance.

scholarly journals Early Macrophage Infiltrates Impair Pancreatic Cancer Cell Growth by TNF-a Secretion

2020 ◽  
Author(s):  
Cansu Tekin ◽  
Hella L Aberson ◽  
Maarten F Bijlsma ◽  
C. Arnold Spek
Keyword(s):  
Cell Death ◽  
Conditioned Medium ◽  
Cell Lines ◽  
Annexin V ◽  
Therapeutic Benefit ◽  
Ductal Adenocarcinoma ◽  
Potential Candidate ◽  
Cancer Cell Growth

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is a disease with high mortality rates. Increased macrophage influx in PDAC is common and associated with poor prognosis. Macrophages are highly plastic cells that can exhibit both anti- and pro-tumorigenic properties. Here, we investigated how naïve (M0) macrophages differ from other macrophages in their anti-tumorigenic activities.Methods: In vitro BrdU proliferation and Annexin V cell death analyses were performed on PANC-1 and MIA PaCa-2 PDAC cell lines exposed to conditioned medium of known macrophage subsets. Macrophage secreted molecules were measured by transcript analysis and ELISA. Therapeutic antibodies were used to functionally establish the role of the identified cytokine in PDAC proliferation.Results: Proliferation and cell death assays revealed that only M0 macrophages exert anti-tumorigenic activities and that M1, M2, and TAMs do not. mRNA analysis and ELISA results suggested TNF-a as a potential candidate to mediate M0 macrophage induced cell death. To prove or refute the importance of TNF-a in M0 macrophage-induced cell death, PANC-1 and MIA PaCa-2 cell-lines were exposed to M0 macrophage conditioned medium in the presence of the TNF-a inhibitor infliximab, which effectively diminished the anti-tumor activities of M0 macrophages.Conclusion: Freshly infiltrated naive M0 macrophages exert anti-tumorigenic activities via TNF-a secretion. Their subsequent differentiation into either M1, M2, or TAM subsets reduces TNF-a levels, thereby abolishing their cytotoxic activity on PDAC cells. These data suggest that the restoration of TNF-a secretion in differentiated macrophages might yield a therapeutic benefit.

The Role of Sense of Direction and Other Factors During Navigation in a Large-Scale, Unconstrained Environment

2013 ◽  
Author(s):  
Elisabeth J. Ploran ◽  
Ericka Rovira ◽  
James C. Thompson ◽  
Raja Parasuraman
Keyword(s):  
Large Scale ◽  
Sense Of Direction
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