Autophagic Degradation Is Involved in Cell Protection against Ricin Toxin

Wu, Yu; Taisne, Clémence; Mahtal, Nassim; Forrester, Alison; Lussignol, Marion; Cintrat, Jean‐Christophe; Esclatine, Audrey; Gillet, Daniel; Barbier, Julien

doi:10.3390/toxins15050304

Cited by 7 publications

(4 citation statements)

References 49 publications

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“…This represents a fundamental requirement in anti-cancer therapy, since the use of drugs, able to trigger multiple death pathways, can avoid the selection of resistant clones. Further studies will be necessary to identify the involvement of autophagy and/or endoplasmic reticulum stress, which have been already described for some RIPs [ 16 , 47 , 48 , 49 , 50 , 51 , 52 ].…”

Section: Discussionmentioning

confidence: 99%

Heterophyllin: A New Adenia Toxic Lectin with Peculiar Biological Properties

Bortolotti,

Biscotti,

Zanello

et al. 2023

Toxins

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Ribosome-inactivating proteins (RIPs) are plant toxins that were identified for their ability to irreversibly damage ribosomes, thereby causing arrest of protein synthesis and induction of cell death. The RIPs purified from Adenia plants are the most potent ones. Here, we describe a novel toxic lectin from Adenia heterophylla caudex, which has been named heterophyllin. Heterophyllin shows the enzymatic and lectin properties of type 2 RIPs. Interestingly, in immunoreactivity experiments, heterophyllin poorly cross-reacts with sera against all other tested RIPs. The cytotoxic effects and death pathways triggered by heterophyllin were investigated in three human-derived cell lines: NB100, T24, and MCF7, and compared to ricin, the most known and studied type 2 RIP. Heterophyllin was able to completely abolish cell viability at nM concentration. A strong induction of apoptosis, but not necrosis, and the involvement of oxidative stress and necroptosis were observed in all the tested cell lines. Therefore, the enzymatic, immunological, and biological activities of heterophyllin make it an interesting molecule, worthy of further in-depth analysis to verify its possible pharmacological application.

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Section: Discussionmentioning

confidence: 99%

Heterophyllin: A New Adenia Toxic Lectin with Peculiar Biological Properties

Bortolotti,

Biscotti,

Zanello

et al. 2023

Toxins

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show abstract

“…In the context of ubiquitin-like proteins, another important emerging player is autophagy. Autophagic programmed cell death is a complex and highly regulated degradative process, which acts as a survival pathway in response to cellular stress [ 27 ]. Autophagic programmed cell death of the meristematic cells has been implicated in the root-tip death of several species, such as pea and maize, when exposed to severe stress conditions [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Biochemical Analysis to Understand the Flooding Tolerance of Mutant Soybean Irradiated with Gamma Rays

Komatsu,

Zhou,

Kono

2023

IJMS

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Flooding stress, which reduces plant growth and seed yield, is a serious problem for soybean. To improve the productivity of flooded soybean, flooding-tolerant soybean was produced by gamma-ray irradiation. Three-day-old wild-type and mutant-line plants were flooded for 2 days. Protein, RNA, and genomic DNA were then analyzed based on oppositely changed proteins between the wild type and the mutant line under flooding stress. They were associated with cell organization, RNA metabolism, and protein degradation according to proteomic analysis. Immunoblot analysis confirmed that the accumulation of beta-tubulin/beta-actin increased in the wild type under flooding stress and recovered to the control level in the mutant line; however, alpha-tubulin increased in both the wild type and the mutant line under stress. Ubiquitin was accumulated and genomic DNA was degraded by flooding stress in the wild type; however, they were almost the same as control levels in the mutant line. On the other hand, the gene expression level of RNase H and 60S ribosomal protein did not change in either the wild type or the mutant line under flooding stress. Furthermore, chlorophyll a/b decreased and increased in the wild type and the mutant line, respectively, under flooding stress. These results suggest that the regulation of cell organization and protein degradation might be an important factor in the acquisition of flooding tolerance in soybean.

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“…The mean tumor weight was significantly reduced with pierisin-1 treatment, and anti-cancer activity in vivo was demonstrated [ 40 ]. The LD50 of pierisin-1 was found to be ~5 μg/kg when pierisin-1 was intraperitoneally injected into the mice [ 41 ], showing strong toxicity comparable to that of typical toxic substances such as Diphtheria toxin [ 9 , 10 , 11 , 12 ], Pseudomonas exotoxin [ 42 , 43 , 44 , 45 ], and ricin [ 46 , 47 ].…”

Section: Discovery and Characterization Of Pierisin-1mentioning

confidence: 99%

Pierisin, Cytotoxic and Apoptosis-Inducing DNA ADP-Ribosylating Protein in Cabbage Butterfly

Takahashi-Nakaguchi,

Horiuchi,

Yamamoto

et al. 2024

Toxins

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Pierisin-1 was serendipitously discovered as a strong cytotoxic and apoptosis-inducing protein from pupae of the cabbage butterfly Pieris rapae against cancer cell lines. This 98-kDa protein consists of the N-terminal region (27 kDa) and C-terminal region (71 kDa), and analysis of their biological function revealed that pierisin-1 binds to cell surface glycosphingolipids on the C-terminal side, is taken up into the cell, and is cleaved to N- and C-terminal portions, where the N-terminal portion mono-ADP-ribosylates the guanine base of DNA in the presence of NAD to induce cellular genetic mutation and apoptosis. Unlike other ADP-ribosyltransferases, pieisin-1 was first found to exhibit DNA mono-ADP-ribosylating activity and show anti-cancer activity in vitro and in vivo against various cancer cell lines. Pierisin-1 was most abundantly produced during the transition from the final larval stage to the pupal stage of the cabbage butterfly, and this production was regulated by ecdysteroid hormones. This suggests that pierisn-1 might play a pivotal role in the process of metamorphosis. Moreover, pierisin-1 could contribute as a defense factor against parasitization and microbial infections in the cabbage butterfly. Pierisin-like proteins in butterflies were shown to be present not only among the subtribe Pierina but also among the subtribes Aporiina and Appiadina, and pierisin-2, -3, and -4 were identified in these butterflies. Furthermore, DNA ADP-ribosylating activities were found in six different edible clams. Understanding of the biological nature of pierisin-1 with DNA mono-ADP-ribosylating activity could open up exciting avenues for research and potential therapeutic applications, making it a subject of great interest in the field of molecular biology and biotechnology.

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Autophagic Degradation Is Involved in Cell Protection against Ricin Toxin

Cited by 7 publications

References 49 publications

Heterophyllin: A New Adenia Toxic Lectin with Peculiar Biological Properties

Heterophyllin: A New Adenia Toxic Lectin with Peculiar Biological Properties

Biochemical Analysis to Understand the Flooding Tolerance of Mutant Soybean Irradiated with Gamma Rays

Pierisin, Cytotoxic and Apoptosis-Inducing DNA ADP-Ribosylating Protein in Cabbage Butterfly

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