A Novel Interaction Between Aquaporin 1 and Caspase-3 in Pulmonary Arterial Smooth Muscle Cells

Niedermeyer, S.; Yun, X.; Trujillo, M.; Andrade, M.; Kolb, T.; Suresh, K.; Damarla, M.; Shimoda, L.

doi:10.1101/2023.10.05.561144

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bioRxiv · 10.1101/2023.10.05.561144

A Novel Interaction Between Aquaporin 1 and Caspase-3 in Pulmonary Arterial Smooth Muscle Cells

Niedermeyer, S.·Yun, X.·Trujillo, M.·Andrade, M.·Kolb, T.·Suresh, K.·Damarla, M.·Shimoda, L.

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Abstract

Pulmonary arterial hypertension (PAH) is a disease in which remodeling of the precapillary pulmonary vasculature leads to hyperplasia and hypertrophy of the muscular vascular wall, and the formation of vaso-occlusive lesions. These pathologic changes are predominantly due to abnormal proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs), enhanced cellular functions that have been linked to increases in the cell membrane protein aquaporin-1 (AQP1). However, the mechanisms underlying increased AQP1 abundance have not been fully elucidated. Here we present data that establishes a novel interaction between AQP1 and the proteolytic enzyme caspase-3. In silico analysis of the AQP1 protein reveals two caspase-3 cleavage sites on its c-terminal tail, proximal to known ubiquitin sites. Using biotin proximity ligase techniques, we establish that AQP1 and caspase-3 interact in both HEK293A cells and rat PASMCs. Furthermore, we demonstrate that AQP1 levels increase and decrease with enhanced caspase-3 activity and inhibition respectively. Ultimately, further work characterizing this interaction could provide the foundation for novel PAH therapeutics.

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Niedermeyer, S., Yun, X., Trujillo, M., Andrade, M., Kolb, T., Suresh, K., Damarla, M., Shimoda, L.. 2023-10-06. A Novel Interaction Between Aquaporin 1 and Caspase-3 in Pulmonary Arterial Smooth Muscle Cells. https://doi.org/10.1101/2023.10.05.561144

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