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

Am J Physiol Lung Cell Mol Physiol. 2024 Feb 20. doi: 10.1152/ajplung.00017.2024. Online ahead of print.ABSTRACTPulmonary hypertension (PH) is a condition in which remodeling of the pulmonary vasculature leads to hypertrophy of the muscular vascular wall and extension of muscle into non-muscular arteries. 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 PH therapeutics.PMID:38375595 | DOI:10.1152/ajplung.00017.2024
Source: Am J Physiol Lung Ce... - Category: Respiratory Medicine Authors: Source Type: research