The role of fungal tremorgens in ryegrass staggers

Gallagher, Rex T.; Keogh, R. G.; Latch, G. C. M.; Reid, C. S. W.

doi:10.1080/00288233.1977.10427356

Cited by 40 publications

(17 citation statements)

References 15 publications

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“…7 x 10-7M) and a 150% increase in Vmax (Vmax = 5.0 x 10-13 mole/,ug P/min) relative to control values (Km = 2.2 x 10-7M; Vmax = 2.0 x 10-l3 mole/4g P/min). These values returned to approximate control levels by1 week post-injection (Km = 2.6 x 10-7M; Vmax = 2.13 mole/tg P/min), and then decreased by 77% (Km = 0.5 x 10-M) and 45% Vmax = 1.1 x 10-'3 mole/pg P/min) by 2 weeks. Statistical analysis of these data Lineweaver-Burk plot of 3H-glutamate uptake.…”

mentioning

confidence: 77%

“…Uptake: In Vivo Toxin Exposure. Rats (N = 12) were given intraperitoneal injections of either DMSO or a tremorgenic dose of aflatrem (3 mg/kg IP), and decapitated at 24 hr, 1 week, and 2 weeks after the injection. Day of injection was staggered so that any given experiment contained tissue from rats killed at each time point post-injection.…”

Section: Methodsmentioning

confidence: 99%

“…A group of fungal metabolites collectively known as tremorgenic mycotoxins have been identified as the causative agents of a neurological disease of cattle known as "staggers syndrome" (1). This disease is characterized by muscle tremors and hyperexcitability, and similar responses have been observed in laboratory animals treated with the mycotoxins (2,3).…”

Section: Introductionmentioning

confidence: 98%

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Aflatrem: a tremorgenic mycotoxin with acute neurotoxic effects.

Valdés¹,

Cameron²,

Cole³

1985

Environ Health Perspect

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Tremorgenic mycotoxins induce neurologic symptoms ranging from mental confusion to tremors, seizures and death, and are apparently the only class of mycotoxins with significant central nervous system activity. Tremorgens have been implicated in a number of neurologic diseases of cattle collectively known as staggers syndromes, and pose significant agricultural and health problems for both cattle and humans. Although the effects of tremorgens are thought to result from transient perturbations of amino acid neurotransmitter release mechanisms, there is reason to believe that acute exposures to toxins with such synaptic effects may result in degeneration of neuronal fiber processes. To test this hypothesis, rats were given a single tremorgenic (3 mg/kg, IP) dose of aflatrem, and kinetics of amino acid neurotransmitter uptake was assessed in isolated hippocampal nerve terminals at 1 day, 1 week, and 2 weeks after injection. Results indicate a decrease in the capacity of the GABA and glutamate uptake systems, which was interpreted as a loss of nerve terminals. The affinity constants suggest a decrease in release of these transmitters as well. In addition to its transient influence on transmitter release, a single low dose of aflatrem is able to induce degeneration of neuronal processes in hippocampal neurotransmitter systems and therefore represents a long-term health threat.

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mentioning

confidence: 77%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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Aflatrem: a tremorgenic mycotoxin with acute neurotoxic effects.

Valdés¹,

Cameron²,

Cole³

1985

Environ Health Perspect

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“…Molds producing such tremorgens pose a recognized health risk to humans and animals when these microorganisms are present in spoiled food or feed. For example, livestock grazing on moldy pastures may develop sporadic locomotor incoordination, where they may stagger, fall over, and suffer muscular spasms [5], [6]. However, the mode of action for many of these mycotoxins has not been elucidated in detail.…”

Section: Introductionmentioning

confidence: 99%

Repositioning of Verrucosidin, a Purported Inhibitor of Chaperone Protein GRP78, as an Inhibitor of Mitochondrial Electron Transport Chain Complex I

et al. 2013

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Verrucosidin (VCD) belongs to a group of fungal metabolites that were identified in screening programs to detect molecules that preferentially kill cancer cells under glucose-deprived conditions. Its mode of action was proposed to involve inhibition of increased GRP78 (glucose regulated protein 78) expression during hypoglycemia. Because GRP78 plays an important role in tumorigenesis, inhibitors such as VCD might harbor cancer therapeutic potential. We therefore sought to characterize VCD’s anticancer activity in vitro. Triple-negative breast cancer cell lines MDA-MB-231 and MDA-MB-468 were treated with VCD under different conditions known to trigger increased expression of GRP78, and a variety of cellular processes were analyzed. We show that VCD was highly cytotoxic only under hypoglycemic conditions, but not in the presence of normal glucose levels, and VCD blocked GRP78 expression only when glycolysis was impaired (due to hypoglycemia or the presence of the glycolysis inhibitor 2-deoxyglucose), but not when GRP78 was induced by other means (hypoxia, thapsigargin, tunicamycin). However, VCD’s strictly hypoglycemia-specific toxicity was not due to the inhibition of GRP78. Rather, VCD blocked mitochondrial energy production via inhibition of complex I of the electron transport chain. As a result, cellular ATP levels were quickly depleted under hypoglycemic conditions, and common cellular functions, including general protein synthesis, deteriorated and resulted in cell death. Altogether, our study identifies mitochondria as the primary target of VCD. The possibility that other purported GRP78 inhibitors (arctigenin, biguanides, deoxyverrucosidin, efrapeptin, JBIR, piericidin, prunustatin, pyrvinium, rottlerin, valinomycin, versipelostatin) might act in a similar GRP78-independent fashion will be discussed.

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“…in the aetiology of rye grass staggers, a disease of grazing animals in New Zealand, Australia, and possibly Britain, is under investigation (di Menna et al 1976;Gallagher et al 1977;di Menna & Mantle 1978;Shreeve et al 1978;Lanigan et aI. 1979;Day & Mantle 1980).…”

Section: Introductionmentioning

confidence: 99%

An immunofluorescent counting method for tremorgenic penicillia

Wyatt

Menna

1981

New Zealand Journal of Agricultural Research

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Antibodies produced against tremorgenic strains of Penicillium crustosum and Penicilliumjanczewskii, conjugated indirectly with fluorescein, were used to stain mycelium of pure cultures of moulds and also hyphae present in natural substrates.There was strong fluorescent staining of strains of nine of 11 Penicillium species known to produce tremorgens and a variable staining reaction of two. Strains of seven of 11 non-tremorgenic Penicillium species did not react, three stained weakly or variably and one stained strongly. None of the isolates of 17 other mould genera examined, including tremorgenic strains of Aspergillus spp., was reactive. Fluorescent hyphae were seen in preparations of soil suspensions and plant washings from which reactive Penicillia were isolated by culture on dilution plates.

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The role of fungal tremorgens in ryegrass staggers

Cited by 40 publications

References 15 publications

Aflatrem: a tremorgenic mycotoxin with acute neurotoxic effects.

Aflatrem: a tremorgenic mycotoxin with acute neurotoxic effects.

Repositioning of Verrucosidin, a Purported Inhibitor of Chaperone Protein GRP78, as an Inhibitor of Mitochondrial Electron Transport Chain Complex I

An immunofluorescent counting method for tremorgenic penicillia

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