The kallikrein-like activity of Heloderma venom is inhibited by carbon monoxide

Nielsen, Vance G.; Frank, Nathaniel

doi:10.1007/s11239-019-01853-6

Cited by 6 publications

(22 citation statements)

References 24 publications

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“…The key element of the paradigm that implicates CO as the mechanism behind the effects of CORMs is the determination that the inactivated releasing molecule (iRM), the portion of the CORM that remains after CO release, has no effect or a different effect on the system tested with the CORM compared to the anticipated CO effect. This laboratory has used this CORM-based paradigm for the past few years to demonstrate that CO inhibited the various procoagulant and anticoagulant activities of hemotoxic venoms and enzymes collected from dozens of snake and lizard species [1][2][3][4][5][6][7][8][9][10][11][12][13]. The particular CORM used was CORM-2 (tricarbonyldichlororuthenium (II) dimer) [1][2][3][4][5][6][7][8][9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

“…This laboratory has used this CORM-based paradigm for the past few years to demonstrate that CO inhibited the various procoagulant and anticoagulant activities of hemotoxic venoms and enzymes collected from dozens of snake and lizard species [1][2][3][4][5][6][7][8][9][10][11][12][13]. The particular CORM used was CORM-2 (tricarbonyldichlororuthenium (II) dimer) [1][2][3][4][5][6][7][8][9][10][11][12][13]. The presumed mechanism was that CO must be interacting with a cryptic heme group attached to the various venoms and enzymes or in some other way interacting with these diverse enzymes and venoms [1][2][3][4][5][6][7][8][9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

“…The particular CORM used was CORM-2 (tricarbonyldichlororuthenium (II) dimer) [1][2][3][4][5][6][7][8][9][10][11][12][13]. The presumed mechanism was that CO must be interacting with a cryptic heme group attached to the various venoms and enzymes or in some other way interacting with these diverse enzymes and venoms [1][2][3][4][5][6][7][8][9][10][11][12][13]. Thus, this potentially heme-based, CO-modulated paradigm of snake venom activity seemed plausible with the aforementioned paradigm of CORM-CO release-inert iRM interactions with target molecules.…”

Section: Introductionmentioning

confidence: 99%

“…While it is unreasonable to reassess all previous venoms inhibited by CORM-2 to determine if a Ru-based radical rather than CO was mediating the inhibition [1][2][3][4][5][6][7][8][9][10][11][12][13], assessing a few representative venoms would be of benefit. To this end, three procoagulant venoms derived from diverse species from Africa and Australia were selected that have already been characterized as inhibited by CORM-2 but not by its iRM by this laboratory [8,10].…”

Section: Introductionmentioning

confidence: 99%

“…Critically, the use of RuCl 3 in this investigation was purely to provide mechanistic insight, and as there is no clinical indication to administer it to humans or any other species, I am not advocating it as a therapeutic option. As previously described [1][2][3][4][5][6][7][8][9][10][11][12][13]15,16], changes in procoagulant activity were assessed with human plasma via changes in coagulation kinetics determined with thrombelastography.…”

Section: Introductionmentioning

confidence: 99%

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Ruthenium, Not Carbon Monoxide, Inhibits the Procoagulant Activity of Atheris, Echis, and Pseudonaja Venoms

Nielsen¹

2020

IJMS

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The demonstration that carbon monoxide releasing molecules (CORMs) affect experimental systems by the release of carbon monoxide, and not via the interaction of the inactivated CORM, has been an accepted paradigm for decades. However, it has recently been documented that a radical intermediate formed during carbon monoxide release from ruthenium (Ru)-based CORM (CORM-2) interacts with histidine and can inactivate bee phospholipase A2 activity. Using a thrombelastographic based paradigm to assess procoagulant activity in human plasma, this study tested the hypothesis that a Ru-based radical and not carbon monoxide was responsible for CORM-2 mediated inhibition of Atheris, Echis, and Pseudonaja species snake venoms. Assessment of the inhibitory effects of ruthenium chloride (RuCl3) on snake venom activity was also determined. CORM-2 mediated inhibition of the three venoms was found to be independent of carbon monoxide release, as the presence of histidine-rich albumin abrogated CORM-2 inhibition. Exposure to RuCl3 had little effect on Atheris venom activity, but Echis and Pseudonaja venom had procoagulant activity significantly reduced. In conclusion, a Ru-based radical and ion inhibited procoagulant snake venoms, not carbon monoxide. These data continue to add to our mechanistic understanding of how Ru-based molecules can modulate hemotoxic venoms, and these results can serve as a rationale to focus on perhaps other, complementary compounds containing Ru as antivenom agents in vitro and, ultimately, in vivo.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ruthenium, Not Carbon Monoxide, Inhibits the Procoagulant Activity of Atheris, Echis, and Pseudonaja Venoms

Nielsen¹

2020

IJMS

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An update on mechanisms of pruritus and their potential treatment in primary cutaneous T-cell lymphoma

Elieh‐Ali‐Komi

Maurer

et al. 2023

Clin Exp Med

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Primary cutaneous T-cell lymphomas (CTCL), which include mycosis fungoides (MF) and Sézary syndrome (SS), are a group of lymphoproliferative disorders characterized by clonal accumulation of neoplastic T-lymphocytes in the skin. Severe pruritus, one of the most common and distressing symptoms in primary CTCL, can significantly impair emotional well-being, physical functioning, and interpersonal relationships, thus greatly reducing quality of life. Unfortunately, effectively managing pruritus remains challenging in CTCL patients as the underlying mechanisms are, as of yet, not fully understood. Previous studies investigating the mechanisms of itch in CTCL have identified several mediators and their corresponding antagonists used for treatment. However, a comprehensive overview of the mediators and receptors contributing to pruritus in primary CTCL is lacking in the current literature. Here, we summarize and review the mediators and receptors that may contribute to pruritus in primary CTCL to explore the mechanisms of CTCL pruritus and identify effective therapeutic targets using the PubMed and Web of Science databases. Studies were included if they described itch mediators and receptors in MF and SS. Overall, the available data suggest that proteases (mainly tryptase), and neuropeptides (particularly Substance P) may be of greatest interest. At the receptor level, cytokine receptors, MRGPRs, and TRP channels are most likely important. Future drug development efforts should concentrate on targeting these mediators and receptors for the treatment of CTCL pruritus.

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The anticoagulant effect of Apis mellifera phospholipase A2 is inhibited by CORM-2 via a carbon monoxide-independent mechanism

Nielsen

2019

J Thromb Thrombolysis

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The kallikrein-like activity of Heloderma venom is inhibited by carbon monoxide

Cited by 6 publications

References 24 publications

Ruthenium, Not Carbon Monoxide, Inhibits the Procoagulant Activity of Atheris, Echis, and Pseudonaja Venoms

Ruthenium, Not Carbon Monoxide, Inhibits the Procoagulant Activity of Atheris, Echis, and Pseudonaja Venoms

An update on mechanisms of pruritus and their potential treatment in primary cutaneous T-cell lymphoma

The anticoagulant effect of Apis mellifera phospholipase A2 is inhibited by CORM-2 via a carbon monoxide-independent mechanism

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