Impacto da inibição de miosina 1c (Myo1c) no processo de angiogênese

Abstract

Class 1 myosins (Myo1s) were the first unconventional myosins identified. Myo1c, a Myo1 isoform, is involved in the regulation of gene expression, cytoskeletal rearrangements, delivery of proteins to the cell surface, cell migration and spreading. Thus, the important role of Myo1c in different biological processes is evident. Therefore, in the present study we investigated the effects of Myo1c inhibition triggered by Pentachloropseudilin (PClP), a reversible and allosteric potent inhibitor of Myo1c, on angiogenesis. We demonstrated that blocking of Myo1c activity by treatment with PClP promoted a decrease in the number of vessels. The observed inhibition of angiogenesis is likely related to the inhibition of cell proliferation, migration, adhesion and alteration of the actin cytoskeleton pattern as shown on PClP-treated HUVEC cell line. Moreover, we also demonstrated that PClP treatment partially prevented the delivery of integrins to the plasma membrane. Finally, we showed that the inhibition of Myo1c caused DNA strand breaks, which is probably repaired during the cell cycle arrest in G1 phase. Taken together, our results suggest Myo1c as an attractive target for drug-based treatment of angiogenesis-related human diseases.