The ACYP2 Knockout SK-HEP-1 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population derived from the SK-HEP-1 hepatic sinusoidal endothelial-like cell line. This product is generated through CRISPR/Cas9-mediated disruption of the ACYP2 gene, resulting in a heterogeneous loss-of-function model suitable for studying acylphosphatase-related biology. This polyclonal population supports bulk metabolic analyses and pooled functional screens without clonal biases.
The SK-HEP-1 host cell line originates from the ascites fluid of a patient with liver adenocarcinoma but exhibits a well-characterized endothelial phenotype, including expression of CD31 and von Willebrand factor (vWF). These cells are widely used as an in vitro model of liver sinusoidal endothelial cells (LSECs), which are critical for hepatic blood filtration, scavenging, and immune tolerance. SK-HEP-1 cells are valuable for studying LSEC functions, drug metabolism, and liver pathophysiology.
ACYP2 encodes an acylphosphatase that hydrolyzes acyl phosphates, primarily acetyl phosphate and carbamoyl phosphate. Through this, it regulates the availability of carbamoyl phosphate for pyrimidine and urea biosynthesis, and acetyl phosphate for protein acetylation. ACYP2 physically interacts with and modulates Na+/K+-ATPase and Ca2+-ATPase, thereby influencing intracellular calcium dynamics. Knockout leads to accumulation of substrates and altered fluxes through pathways involving UMP, urea cycle intermediates (ornithine, citrulline), and Ca2+.
In SK-HEP-1 hepatic endothelial cells, ACYP2 knockout allows dissection of acylphosphate metabolism in LSEC biology. Accumulation of carbamoyl phosphate and acetyl phosphate may perturb pyrimidine synthesis, urea cycle function, and protein acetylation patterns. This model is relevant for studying endothelial contributions to metabolic disorders, drug-induced liver injury, and statin-induced myopathy, where ACYP2 variants are associated with risk. Additionally, altered Ca2+-ATPase activity makes it suitable for calcium signaling studies.
The model supports metabolic flux analysis with stable isotope labeling and LC-MS metabolomics to quantify pyrimidine biosynthesis and urea cycle intermediates. Acylphosphatase activity assays, Fluo-4 calcium flux measurements, and statin sensitivity viability tests are directly applicable. Verification methods include RT-qPCR, Western blot, and Sanger sequencing. Migration assays can assess phenotypic changes. This knockout population enables detailed investigation of ACYP2 in hepatic endothelial-like cells. For further information, please contact Ascent Research.
