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Evaluation of Signaling Pathways Profiling in Human Dermal Endothelial Cells Treated by Snake Venom Cysteine-Rich Secretory Proteins (svCRiSPs) from North American Snakes Using Reverse Phase Protein Array (RPPA)

1
National Natural Toxins Research Center (NNTRC), Texas A&M University-Kingsville, MSC 224, 975 West Avenue B, Kingsville, TX 78363, USA
2
Department of Chemistry, Texas A&M University-Kingsville, MSC 161, Kingsville, TX 78363, USA
3
Institute of Biosciences and Technology, Texas A&M University, Houston, TX 77843, USA
*
Author to whom correspondence should be addressed.
Received: 15 July 2021 / Revised: 25 August 2021 / Accepted: 27 August 2021 / Published: 31 August 2021
Cysteine-Rich Secretory Proteins (CRiSPs) are typically found in many snake venoms; however, the role that these toxins play in the pathophysiology of snakebites is still unclear. Herein, we compared the effects of snake venom CRiSPs (svCRiSPs) from the most medically important species of North American snakes on endothelial cell permeability and vascular permeability. We used reverse phase protein array (RPPA) to identify key signaling molecules on human dermal lymphatic (HDLECs) and blood (HDBECs) endothelial cells treated with svCRiSPs. The results showed that Css-CRiSP isolated from Crotalus scutulatus scutulatus and App-CRiSP from Agkistrodon piscivorus piscivorus are the most potent causes of increase vascular and endothelial permeability in comparison with other svCRiSPs used in this study. We examined the protein expression levels and their activated phosphorylation states in HDLECs and HDBECs induced by App-CRiSP and Css-CRiSP using RPPA. Interestingly, both App-CRiSP and Css-CRiSP induced caveolin-1 expression in HDBECs. We also found that stimulating HDBECs with Css-CRiSP and App-CRiSP significantly induced the phosphorylation of mTOR and Src, respectively. In HDLECs, Css-CRiSP significantly downregulated the expression of N-Cadherin and phospholipase C-gamma, while App-CRiSP significantly enhanced Akt and JNK phosphorylation. These results suggest that the increased endothelial permeability in HDLECs and HDBECs by Css-CRiSP and App-CRiSP may occur through different pathways. View Full-Text
Keywords: North American snakes; snake venom cysteine-rich secretory proteins (svCRiSPs); endothelial permeability; reverse phase protein arrays (RPPA); signaling pathway North American snakes; snake venom cysteine-rich secretory proteins (svCRiSPs); endothelial permeability; reverse phase protein arrays (RPPA); signaling pathway
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MDPI and ACS Style

Suntravat, M.; Sanchez, O.; Reyes, A.; Cirilo, A.; Ocheltree, J.S.; Galan, J.A.; Salazar, E.; Davies, P.; Sanchez, E.E. Evaluation of Signaling Pathways Profiling in Human Dermal Endothelial Cells Treated by Snake Venom Cysteine-Rich Secretory Proteins (svCRiSPs) from North American Snakes Using Reverse Phase Protein Array (RPPA). Toxins 2021, 13, 613. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13090613

AMA Style

Suntravat M, Sanchez O, Reyes A, Cirilo A, Ocheltree JS, Galan JA, Salazar E, Davies P, Sanchez EE. Evaluation of Signaling Pathways Profiling in Human Dermal Endothelial Cells Treated by Snake Venom Cysteine-Rich Secretory Proteins (svCRiSPs) from North American Snakes Using Reverse Phase Protein Array (RPPA). Toxins. 2021; 13(9):613. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13090613

Chicago/Turabian Style

Suntravat, Montamas, Oscar Sanchez, Armando Reyes, Abcde Cirilo, Jack S. Ocheltree, Jacob A. Galan, Emelyn Salazar, Peter Davies, and Elda E. Sanchez 2021. "Evaluation of Signaling Pathways Profiling in Human Dermal Endothelial Cells Treated by Snake Venom Cysteine-Rich Secretory Proteins (svCRiSPs) from North American Snakes Using Reverse Phase Protein Array (RPPA)" Toxins 13, no. 9: 613. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13090613

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