Toxins

Editorial

Jump to: Research, Review

304 KiB

Open AccessEditorial

Introduction to the Toxins Special Issue on Plant Toxins

by Nilgun E. Tumer

Toxins 2015, 7(11), 4503-4506; https://doi.org/10.3390/toxins7114503 - 2 Nov 2015

Cited by 2 | Viewed by 4741

Abstract

Plants express a variety of toxic proteins which are thought to have a role in defense against pathogens and insects. [...] Full article

(This article belongs to the Special Issue Plant Toxins)

Research

Jump to: Editorial, Review

4731 KiB

Open AccessArticle

Clinical and Pathological Findings Associated with Aerosol Exposure of Macaques to Ricin Toxin

by Seth H. Pincus, Manoj Bhaskaran, Robert N. Brey III, Peter J. Didier, Lara A. Doyle-Meyers and Chad J. Roy

Toxins 2015, 7(6), 2121-2133; https://doi.org/10.3390/toxins7062121 - 9 Jun 2015

Cited by 47 | Viewed by 7395

Abstract

Ricin is a potential bioweapon that could be used against civilian and military personnel. Aerosol exposure is the most likely route of contact to ricin toxin that will result in the most severe toxicity. Early recognition of ricin exposure is essential if specific [...] Read more.

Ricin is a potential bioweapon that could be used against civilian and military personnel. Aerosol exposure is the most likely route of contact to ricin toxin that will result in the most severe toxicity. Early recognition of ricin exposure is essential if specific antidotes are to be applied. Initial diagnosis will most likely be syndromic, i.e., fitting clinical and laboratory signs into a pattern which then will guide the choice of more specific diagnostic assays and therapeutic interventions. We have studied the pathology of ricin toxin in rhesus macaques exposed to lethal and sublethal ricin aerosols. Animals exposed to lethal ricin aerosols were followed clinically using telemetry, by clinical laboratory analyses and by post-mortem examination. Animals exposed to lethal aerosolized ricin developed fever associated with thermal instability, tachycardia, and dyspnea. In the peripheral blood a marked neutrophilia (without immature bands) developed at 24 h. This was accompanied by an increase in monocytes, but depletion of lymphocytes. Red cell indices indicated hemoconcentration, as did serum chemistries, with modest increases in sodium and blood urea nitrogen (BUN). Serum albumin was strikingly decreased. These observations are consistent with the pathological observations of fluid shifts to the lungs, in the form of hemorrhages, inflammatory exudates, and tissue edema. In macaques exposed to sublethal aerosols of ricin, late pathologic consequences included chronic pulmonary fibrosis, likely mediated by M2 macrophages. Early administration of supportive therapy, specific antidotes after exposure or vaccines prior to exposure have the potential to favorably alter this outcome. Full article

(This article belongs to the Special Issue Plant Toxins)

► Show Figures

Graphical abstract

1200 KiB

Open AccessArticle

Toxicity of the Anti-ribosomal Lectin Ebulin f in Lungs and Intestines in Elderly Mice

by Manuel Garrosa, Pilar Jiménez, Jesús Tejero, Patricia Cabrero, Damián Cordoba-Diaz, Emiliano J. Quinto, Manuel J. Gayoso and Tomás Girbés

Toxins 2015, 7(2), 367-379; https://doi.org/10.3390/toxins7020367 - 2 Feb 2015

Cited by 11 | Viewed by 6081

Abstract

All parts of dwarf elder (Sambucus ebulus L.) studied so far contain a ribosome-inactivating protein with lectin activity (ribosome-inactivating lectin; RIL), known as ebulin. Green fruits contain ebulin f, the toxicity of which has been studied in six-week-old mice, where it was [...] Read more.

All parts of dwarf elder (Sambucus ebulus L.) studied so far contain a ribosome-inactivating protein with lectin activity (ribosome-inactivating lectin; RIL), known as ebulin. Green fruits contain ebulin f, the toxicity of which has been studied in six-week-old mice, where it was found that the intestines were primary targets for it when administered intraperitoneally (i.p.). We performed experiments to assess whether ebulin f administration to six- and 12-month-old mice would trigger higher toxicity than that displayed in six-week-old mice. In the present report, we present evidence indicating that the toxicological effects of ebulin f after its i.p. administration to elderly mice are exerted on the lungs and intestines by an increased rate of apoptosis. We hypothesize that the ebulin f apoptosis-promoting action together with the age-dependent high rate of apoptosis result in an increase in the lectin’s toxicity, leading to a higher lethality level. Full article

(This article belongs to the Special Issue Plant Toxins)

► Show Figures

Figure 1

844 KiB

Open AccessArticle

The Recombinant Maize Ribosome-Inactivating Protein Transiently Reduces Viral Load in SHIV89.6 Infected Chinese Rhesus Macaques

by Rui-Rui Wang, Ka-Yee Au, Hong-Yi Zheng, Liang-Min Gao, Xuan Zhang, Rong-Hua Luo, Sue Ka-Yee Law, Amanda Nga-Sze Mak, Kam-Bo Wong, Ming-Xu Zhang, Wei Pang, Gao-Hong Zhang, Pang-Chui Shaw and Yong-Tang Zheng

Toxins 2015, 7(1), 156-169; https://doi.org/10.3390/toxins7010156 - 19 Jan 2015

Cited by 10 | Viewed by 6295

Abstract

Ribosome inactivating proteins (RIPs) inhibit protein synthesis by depurinating the large ribosomal RNA and some are found to possess anti-human immunodeficiency virus (HIV) activity. Maize ribosome inactivating protein (RIP) has an internal inactivation loop which is proteolytically removed for full catalytic activity. Here, [...] Read more.

Ribosome inactivating proteins (RIPs) inhibit protein synthesis by depurinating the large ribosomal RNA and some are found to possess anti-human immunodeficiency virus (HIV) activity. Maize ribosome inactivating protein (RIP) has an internal inactivation loop which is proteolytically removed for full catalytic activity. Here, we showed that the recombinant active maize RIP protected chimeric simian-human immunodeficiency virus (SHIV) 89.6-infected macaque peripheral blood mononuclear cells from lysis ex vivo and transiently reduced plasma viral load in SHIV89.6-infected rhesus macaque model. No evidence of immune dysregulation and other obvious side-effects was found in the treated macaques. Our work demonstrates the potential development of maize RIP as an anti-HIV agent without impeding systemic immune functions. Full article

(This article belongs to the Special Issue Plant Toxins)

► Show Figures

Figure 1

1107 KiB

Open AccessArticle

Triggering Apoptotic Death of Human Epidermal Keratinocytes by Malic Acid: Involvement of Endoplasmic Reticulum Stress- and Mitochondria-Dependent Signaling Pathways

by Yu-Ping Hsiao, Wan-Wen Lai, Shi-Bei Wu, Chung-Hung Tsai, Sheau-Chung Tang, Jing-Gung Chung and Jen-Hung Yang

Toxins 2015, 7(1), 81-96; https://doi.org/10.3390/toxins7010081 - 9 Jan 2015

Cited by 16 | Viewed by 9787

Abstract

Malic acid (MA) has been commonly used in cosmetic products, but the safety reports in skin are sparse. To investigate the biological effects of MA in human skin keratinocytes, we investigated the potential cytotoxicity and apoptotic effects of MA in human keratinocyte cell [...] Read more.

Malic acid (MA) has been commonly used in cosmetic products, but the safety reports in skin are sparse. To investigate the biological effects of MA in human skin keratinocytes, we investigated the potential cytotoxicity and apoptotic effects of MA in human keratinocyte cell lines (HaCaT). The data showed that MA induced apoptosis based on the observations of DAPI staining, DNA fragmentation, and sub-G1 phase in HaCaT cells and normal human epidermal keratinocytes (NHEKs). Flow cytometric assays also showed that MA increased the production of mitochondrial superoxide (mito-SOX) but decreased the mitochondrial membrane potential. Analysis of bioenergetics function with the XF 24 analyzer Seahorse extracellular flux analyzer demonstrated that oxygen consumption rate (OCR) was significantly decreased whereas extracellular acidification rate (ECAR) was increased in MA-treated keratinocytes. The occurrence of apoptosis was proved by the increased expressions of FasL, Fas, Bax, Bid, caspases-3, -8, -9, cytochrome c, and the declined expressions of Bcl-2, PARP. MA also induced endoplasmic reticulum stress associated protein expression such as GRP78, GADD153, and ATF6α. We demonstrated that MA had anti-proliferative effect in HaCaT cell through the inhibition of cell cycle progression at G0/G1, and the induction of programmed cell death through endoplasmic reticulum stress- and mitochondria-dependent pathways. Full article

(This article belongs to the Special Issue Plant Toxins)

► Show Figures

Figure 1

Review

Jump to: Editorial, Research

1637 KiB

Open AccessReview

Ribosome-Inactivating and Related Proteins

by Joachim Schrot, Alexander Weng and Matthias F. Melzig

Toxins 2015, 7(5), 1556-1615; https://doi.org/10.3390/toxins7051556 - 8 May 2015

Cited by 102 | Viewed by 8928

Abstract

Ribosome-inactivating proteins (RIPs) are toxins that act as N-glycosidases (EC 3.2.2.22). They are mainly produced by plants and classified as type 1 RIPs and type 2 RIPs. There are also RIPs and RIP related proteins that cannot be grouped into the classical [...] Read more.

Ribosome-inactivating proteins (RIPs) are toxins that act as N-glycosidases (EC 3.2.2.22). They are mainly produced by plants and classified as type 1 RIPs and type 2 RIPs. There are also RIPs and RIP related proteins that cannot be grouped into the classical type 1 and type 2 RIPs because of their different sizes, structures or functions. In addition, there is still not a uniform nomenclature or classification existing for RIPs. In this review, we give the current status of all known plant RIPs and we make a suggestion about how to unify those RIPs and RIP related proteins that cannot be classified as type 1 or type 2 RIPs. Full article

(This article belongs to the Special Issue Plant Toxins)

1410 KiB

Open AccessReview

Pokeweed Antiviral Protein: Its Cytotoxicity Mechanism and Applications in Plant Disease Resistance

by Rong Di and Nilgun E. Tumer

Toxins 2015, 7(3), 755-772; https://doi.org/10.3390/toxins7030755 - 6 Mar 2015

Cited by 39 | Viewed by 7994

Abstract

Pokeweed antiviral protein (PAP) is a 29 kDa type I ribosome inactivating protein (RIP) found in pokeweed plants. Pokeweed produces different forms of PAP. This review focuses on the spring form of PAP isolated from Phytolacca americana leaves. PAP exerts its cytotoxicity by [...] Read more.

Pokeweed antiviral protein (PAP) is a 29 kDa type I ribosome inactivating protein (RIP) found in pokeweed plants. Pokeweed produces different forms of PAP. This review focuses on the spring form of PAP isolated from Phytolacca americana leaves. PAP exerts its cytotoxicity by removing a specific adenine from the α-sarcin/ricin loop of the large ribosomal RNA. Besides depurination of the rRNA, PAP has additional activities that contribute to its cytotoxicity. The mechanism of PAP cytotoxicity is summarized based on evidence from the analysis of transgenic plants and the yeast model system. PAP was initially found to be anti-viral when it was co-inoculated with plant viruses onto plants. Transgenic plants expressing PAP and non-toxic PAP mutants have displayed broad-spectrum resistance to both viral and fungal infection. The mechanism of PAP-induced disease resistance in transgenic plants is summarized. Full article

(This article belongs to the Special Issue Plant Toxins)

► Show Figures

Figure 1

501 KiB

Open AccessReview

Ebulin from Dwarf Elder (Sambucus ebulus L.): A Mini-Review

by Pilar Jiménez, Jesús Tejero, Damián Cordoba-Diaz, Emiliano J. Quinto, Manuel Garrosa, Manuel J. Gayoso and Tomás Girbés

Toxins 2015, 7(3), 648-658; https://doi.org/10.3390/toxins7030648 - 25 Feb 2015

Cited by 27 | Viewed by 8806

Abstract

Sambucus ebulus L. (dwarf elder) is a medicinal plant, the usefulness of which also as food is restricted due to its toxicity. In the last few years, both the chemistry and pharmacology of Sambucus ebulus L. have been investigated. Among the structural and [...] Read more.

Sambucus ebulus L. (dwarf elder) is a medicinal plant, the usefulness of which also as food is restricted due to its toxicity. In the last few years, both the chemistry and pharmacology of Sambucus ebulus L. have been investigated. Among the structural and functional proteins present in the plant, sugar-binding proteins (lectins) with or without anti-ribosomal activity and single chain ribosome-inactivating proteins (RIPs) have been isolated. RIPs are enzymes (E.C. 3.2.2.22) that display N-glycosidase activity on the 28S rRNA subunit, leading to the inhibition of protein synthesis by arresting the step of polypeptide chain elongation. The biological role of all these proteins is as yet unknown. The evidence suggests that they could be involved in the defense of the plant against predators and viruses or/and a nitrogen store, with an impact on the nutritional characteristics and food safety. In this mini-review we describe all the isoforms of ebulin that have to date been isolated from dwarf elder, as well as their functional characteristics and potential uses, whilst highlighting concern regarding ebulin toxicity. Full article

(This article belongs to the Special Issue Plant Toxins)

631 KiB

Open AccessReview

Structures of Eukaryotic Ribosomal Stalk Proteins and Its Complex with Trichosanthin, and Their Implications in Recruiting Ribosome-Inactivating Proteins to the Ribosomes

by Andrew K. H. Choi, Eddie C. K. Wong, Ka-Ming Lee and Kam-Bo Wong

Toxins 2015, 7(3), 638-647; https://doi.org/10.3390/toxins7030638 - 25 Feb 2015

Cited by 29 | Viewed by 9541

Abstract

Ribosome-inactivating proteins (RIP) are RNA N-glycosidases that inactivate ribosomes by specifically depurinating a conserved adenine residue at the α-sarcin/ricin loop of 28S rRNA. Recent studies have pointed to the involvement of the C-terminal domain of the eukaryotic stalk proteins in facilitating [...] Read more.

Ribosome-inactivating proteins (RIP) are RNA N-glycosidases that inactivate ribosomes by specifically depurinating a conserved adenine residue at the α-sarcin/ricin loop of 28S rRNA. Recent studies have pointed to the involvement of the C-terminal domain of the eukaryotic stalk proteins in facilitating the toxic action of RIPs. This review highlights how structural studies of eukaryotic stalk proteins provide insights into the recruitment of RIPs to the ribosomes. Since the C-terminal domain of eukaryotic stalk proteins is involved in specific recognition of elongation factors and some eukaryote-specific RIPs (e.g., trichosanthin and ricin), we postulate that these RIPs may have evolved to hijack the translation-factor-recruiting function of ribosomal stalk in reaching their target site of rRNA. Full article

(This article belongs to the Special Issue Plant Toxins)

► Show Figures

Figure 1

462 KiB

Open AccessReview

Pokeweed Antiviral Protein, a Ribosome Inactivating Protein: Activity, Inhibition and Prospects

by Artem V. Domashevskiy and Dixie J. Goss

Toxins 2015, 7(2), 274-298; https://doi.org/10.3390/toxins7020274 - 28 Jan 2015

Cited by 42 | Viewed by 12937

Abstract

Viruses employ an array of elaborate strategies to overcome plant defense mechanisms and must adapt to the requirements of the host translational systems. Pokeweed antiviral protein (PAP) from Phytolacca americana is a ribosome inactivating protein (RIP) and is an RNA N-glycosidase that [...] Read more.

Viruses employ an array of elaborate strategies to overcome plant defense mechanisms and must adapt to the requirements of the host translational systems. Pokeweed antiviral protein (PAP) from Phytolacca americana is a ribosome inactivating protein (RIP) and is an RNA N-glycosidase that removes specific purine residues from the sarcin/ricin (S/R) loop of large rRNA, arresting protein synthesis at the translocation step. PAP is thought to play an important role in the plant’s defense mechanism against foreign pathogens. This review focuses on the structure, function, and the relationship of PAP to other RIPs, discusses molecular aspects of PAP antiviral activity, the novel inhibition of this plant toxin by a virus counteraction—a peptide linked to the viral genome (VPg), and possible applications of RIP-conjugated immunotoxins in cancer therapeutics. Full article

(This article belongs to the Special Issue Plant Toxins)

► Show Figures

Graphical abstract

712 KiB

Open AccessReview

Important Poisonous Plants in Tibetan Ethnomedicine

by Lijuan Ma, Ronghui Gu, Li Tang, Ze-E Chen, Rong Di and Chunlin Long

Toxins 2015, 7(1), 138-155; https://doi.org/10.3390/toxins7010138 - 14 Jan 2015

Cited by 53 | Viewed by 18146

Abstract

Tibetan ethnomedicine is famous worldwide, both for its high effectiveness and unique cultural background. Many poisonous plants have been widely used to treat disorders in the Tibetan medicinal system. In the present review article, some representative poisonous plant species are introduced in terms [...] Read more.

Tibetan ethnomedicine is famous worldwide, both for its high effectiveness and unique cultural background. Many poisonous plants have been widely used to treat disorders in the Tibetan medicinal system. In the present review article, some representative poisonous plant species are introduced in terms of their significance in traditional Tibetan medicinal practices. They are Aconitum pendulum, Strychnos nux-vomica, Datura stramonium and Anisodus tanguticus, for which the toxic chemical constituents, bioactivities and pharmacological functions are reviewed herein. The most important toxins include aconitine, strychnine, scopolamine, and anisodamine. These toxic plants are still currently in use for pain-reduction and other purposes by Tibetan healers after processing. Full article

(This article belongs to the Special Issue Plant Toxins)

► Show Figures

Figure 1

806 KiB

Open AccessReview

Ricin Trafficking in Cells

by Robert A. Spooner and J. Michael Lord

Toxins 2015, 7(1), 49-65; https://doi.org/10.3390/toxins7010049 - 9 Jan 2015

Cited by 72 | Viewed by 10398

Abstract

The heterodimeric plant toxin ricin binds exposed galactosyls at the cell surface of target mammalian cells, and, following endocytosis, is transported in vesicular carriers to the endoplasmic reticulum (ER). Subsequently, the cell-binding B chain (RTB) and the catalytic A chain (RTA) are separated [...] Read more.

The heterodimeric plant toxin ricin binds exposed galactosyls at the cell surface of target mammalian cells, and, following endocytosis, is transported in vesicular carriers to the endoplasmic reticulum (ER). Subsequently, the cell-binding B chain (RTB) and the catalytic A chain (RTA) are separated reductively, RTA embeds in the ER membrane and then retrotranslocates (or dislocates) across this membrane. The protein conducting channels used by RTA are usually regarded as part of the ER-associated protein degradation system (ERAD) that removes misfolded proteins from the ER for destruction by the cytosolic proteasomes. However, unlike ERAD substrates, cytosolic RTA avoids destruction and folds into a catalytic conformation that inactivates its target ribosomes. Protein synthesis ceases, and subsequently the cells die apoptotically. This raises questions about how this protein avoids the pathways that are normally sanctioned for ER-dislocating substrates. In this review we focus on the molecular events that occur with non-tagged ricin and its isolated subunits at the ER–cytosol interface. This focus reveals that intra-membrane interactions of RTA may control its fate, an area that warrants further investigation. Full article

(This article belongs to the Special Issue Plant Toxins)

► Show Figures

Figure 1

459 KiB

Open AccessReview

Aconitum Alkaloid Poisoning Related to the Culinary Uses of Aconite Roots

by Thomas Y. K. Chan

Toxins 2014, 6(9), 2605-2611; https://doi.org/10.3390/toxins6092605 - 2 Sep 2014

Cited by 50 | Viewed by 9044

Abstract

Aconite roots (roots or root tubers of the Aconitum species) are eaten as root vegetables and used to prepare herbal soups and meals, mainly for their purported health benefits. Aconite roots contain aconitine and other Aconitum alkaloids, which are well known cardiotoxins and [...] Read more.

Aconite roots (roots or root tubers of the Aconitum species) are eaten as root vegetables and used to prepare herbal soups and meals, mainly for their purported health benefits. Aconite roots contain aconitine and other Aconitum alkaloids, which are well known cardiotoxins and neurotoxins. To better understand why Aconitum alkaloid poisoning related to the culinary uses of aconite roots can occur and characterize the risks posed by these “food supplements”, relevant published reports were reviewed. From 1995 to 2013, there were eight reports of aconite poisoning after consumption of these herbal soups and meals, including two reports of large clusters of cases (n = 19–45) and two reports of cases (n = 15–156) managed by two hospitals over a period of 4.5 to 5 years. The herbal formulae used did not adhere to the suggested guidelines, with regarding to the doses (50–500 g instead of 3–30 g per person) and types (raw instead of processed) of aconite roots used. The quantities of Aconitum alkaloids involved were huge, taking into consideration the doses of aconite roots used to prepare herbal soups/meals and the amounts of aconite roots and herbal soups/meals consumed. In a large cluster of cases, despite simmering raw “caowu” (the root tuber of A. kusnezoffii) in pork broth for 24 h, all 19 family members who consumed this soup and boiled “caowu” developed poisoning. Severe or even fatal aconite poisoning can occur after consumption of herbal soups and foods prepared from aconite roots. Even prolonged boiling may not be protective if raw preparations and large quantities of aconite roots are used. The public should be warned of the risk of severe poisoning related to the culinary and traditional medicinal uses of aconite roots. Full article

(This article belongs to the Special Issue Plant Toxins)

Journal Menu

Journal Browser

Plant Toxins

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (13 papers)

Editorial

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI