The two faces of cyanide: an environmental toxin and a potential novel mammalian gasotransmitter

Zuhra, Karim; Szabó, Csaba

doi:10.1111/febs.16135

Cited by 44 publications

(20 citation statements)

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“…At high concentrations, cyanide becomes toxic to living organisms. Apart from its toxic nature, cyanide is well-known for its metabolic inhibitory effects [ 47 , 48 ]. This may also affect the extracellular secretion by fungi.…”

Section: Resultsmentioning

confidence: 99%

Lovastatin production by an oleaginous fungus, Aspergillus terreus KPR12 using sago processing wastewater (SWW)

2022

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Background Lovastatin is one of the first statins to be extensively used for its cholesterol-lowering ability. It is commercially produced by fermentation. Species belonging to the genus Aspergillus are well-studied fungi that have been widely used for lovastatin production. In the present study, we produced lovastatin from sago processing wastewater (SWW) under submerged fermentation using oleaginous fungal strains, A. terreus KPR12 and A. caespitosus ASEF14. Results The intra- and extracellular concentrations of lovastatin produced by A. terreus KPR12 and A. caespitosus ASEF14 were lactonized. Because A. caespitosus ASEF14 produced a negligible amount of lovastatin, further kinetics of lovastatin production in SWW was studied using the KPR12 strain for 9 days. Lovastatin concentrations in the intra- and extracellular fractions of the A. terreus KPR12 cultured in a synthetic medium (SM) were 117.93 and 883.28 mg L–1, respectively. However, these concentrations in SWW were 142.23 and 429.98 mg L–1, respectively. The yeast growth inhibition bioassay confirmed the antifungal property of fungal extracts. A. terreus KPR12 showed a higher inhibition zone of 14 mm than the ASEF14 strain. The two-way analysis of variance (ANOVA; p < 0.01) showed significant differences in the localization pattern, fungal strains, growth medium, and their respective interactions. The lovastatin yield coefficient values were 0.153 g g–1 on biomass (YLOV/X) and 0.043 g g–1 on the substrate, starch (YLOV/S). The pollutant level of treated SWW exhibited a reduction in total solids (TS, 59%), total dissolved solids (TDS, 68%), biological oxygen demand (BOD, 79.5%), chemical oxygen demand (COD, 57.1%), phosphate (88%), cyanide (65.4%), and void of nutrients such as nitrate (100%), and ammonia (100%). Conclusion The starch-rich wastewater serves as a suitable medium for A. terreus KPR12 for the production of lovastatin. It simultaneously decontaminates the sago processing wastewater, enabling its reuse for irrigation/recreation. Graphical Abstract

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Section: Resultsmentioning

confidence: 99%

Lovastatin production by an oleaginous fungus, Aspergillus terreus KPR12 using sago processing wastewater (SWW)

2022

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“…In turn, the mitochondrial enzyme rhodanese detoxifies cyanide by conversion to thiocyanate. Cyanide's principle target is cytochrome c oxidase-an indispensable enzyme for operative mitochondrial respiration [18]. Consequently, inhibition of mitochondrial electron transport and aerobic ATP generation would critically impair the function of all cells, especially those with a high bioenergetic turnover, such as cancer cells [18].…”

Section: Discussionmentioning

confidence: 99%

“…Cyanide's principle target is cytochrome c oxidase-an indispensable enzyme for operative mitochondrial respiration [18]. Consequently, inhibition of mitochondrial electron transport and aerobic ATP generation would critically impair the function of all cells, especially those with a high bioenergetic turnover, such as cancer cells [18]. In the past, amygdalin has been shown to be a potent inhibitor of cell growth in several neoplasms, e.g., bladder, breast, and pancreatic cancer as well as renal cell carcinoma [19][20][21].…”

Section: Discussionmentioning

confidence: 99%

Amygdalin Exerts Antitumor Activity in Taxane-Resistant Prostate Cancer Cells

Tsaur

Thomas

Monecke

et al. 2022

Cancers

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Despite recent advances in the treatment of metastatic prostate cancer (PCa), resistance development after taxane treatments is inevitable, necessitating effective options to combat drug resistance. Previous studies indicated antitumoral properties of the natural compound amygdalin. However, whether amygdalin acts on drug-resistant tumor cells remains questionable. An in vitro study was performed to investigate the influence of amygdalin (10 mg/mL) on the growth of a panel of therapy-naïve and docetaxel- or cabazitaxel-resistant PCa cell lines (PC3, DU145, and LNCaP cells). Tumor growth, proliferation, clonal growth, and cell cycle progression were investigated. The cell cycle regulating proteins (phospho)cdk1, (phospho)cdk2, cyclin A, cyclin B, p21, and p27 and the mammalian target of rapamycin (mTOR) pathway proteins (phospho)Akt, (phospho)Raptor, and (phospho)Rictor as well as integrin β1 and the cytoskeletal proteins vimentin, ezrin, talin, and cytokeratin 8/18 were assessed. Furthermore, chemotactic activity and adhesion to extracellular matrix components were analyzed. Amygdalin dose-dependently inhibited tumor growth and reduced tumor clones in all (parental and resistant) PCa cell lines, accompanied by a G0/G1 phase accumulation. Cell cycle regulating proteins were significantly altered by amygdalin. A moderate influence of amygdalin on tumor cell adhesion and chemotaxis was observed as well, paralleled by modifications of cytoskeletal proteins and the integrin β1 expression level. Amygdalin may, therefore, block tumor growth and disseminative characteristics of taxane-resistant PCa cells. Further studies are warranted to determine amygdalin’s value as an antitumor drug.

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“…Even though cyanide (CN − )—a highly cytotoxic molecule that inhibits COX to suppress mitochondrial respiration and ATP production, and elevates ROS by modulating antioxidant defense—is proposed to be a novel mammalian gasotransmitter that can stimulate COX activity and enhance cellular bioenergetics at low endogenous nanomolar levels, at levels beyond 10 μM, CN − remains exceedingly toxic [ 340 , 341 , 342 , 343 , 344 , 345 ]. As a result, sophisticated dual-response sensors and probes are used to detect fluctuations in mitochondria viscosity in the presence of varying levels of cyanide in living cells [ 278 , 346 ].…”

Section: Light Water and Melatonin: Ancient Synergies In A Modern Worldmentioning

confidence: 99%

Light, Water, and Melatonin: The Synergistic Regulation of Phase Separation in Dementia

Loh¹,

Reíter

2023

IJMS

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The swift rise in acceptance of molecular principles defining phase separation by a broad array of scientific disciplines is shadowed by increasing discoveries linking phase separation to pathological aggregations associated with numerous neurodegenerative disorders, including Alzheimer’s disease, that contribute to dementia. Phase separation is powered by multivalent macromolecular interactions. Importantly, the release of water molecules from protein hydration shells into bulk creates entropic gains that promote phase separation and the subsequent generation of insoluble cytotoxic aggregates that drive healthy brain cells into diseased states. Higher viscosity in interfacial waters and limited hydration in interiors of biomolecular condensates facilitate phase separation. Light, water, and melatonin constitute an ancient synergy that ensures adequate protein hydration to prevent aberrant phase separation. The 670 nm visible red wavelength found in sunlight and employed in photobiomodulation reduces interfacial and mitochondrial matrix viscosity to enhance ATP production via increasing ATP synthase motor efficiency. Melatonin is a potent antioxidant that lowers viscosity to increase ATP by scavenging excess reactive oxygen species and free radicals. Reduced viscosity by light and melatonin elevates the availability of free water molecules that allow melatonin to adopt favorable conformations that enhance intrinsic features, including binding interactions with adenosine that reinforces the adenosine moiety effect of ATP responsible for preventing water removal that causes hydrophobic collapse and aggregation in phase separation. Precise recalibration of interspecies melatonin dosages that account for differences in metabolic rates and bioavailability will ensure the efficacious reinstatement of the once-powerful ancient synergy between light, water, and melatonin in a modern world.

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The two faces of cyanide: an environmental toxin and a potential novel mammalian gasotransmitter

Abstract: This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as

Cited by 44 publications

References 300 publications

Lovastatin production by an oleaginous fungus, Aspergillus terreus KPR12 using sago processing wastewater (SWW)

Lovastatin production by an oleaginous fungus, Aspergillus terreus KPR12 using sago processing wastewater (SWW)

Amygdalin Exerts Antitumor Activity in Taxane-Resistant Prostate Cancer Cells

Light, Water, and Melatonin: The Synergistic Regulation of Phase Separation in Dementia

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