The CAT Knockout 786-O Polyclonal Cells comprise a CRISPR/Cas9-edited polyclonal knockout cell population derived from the human 786-O renal cell adenocarcinoma line, with targeted disruption of the catalase (CAT) gene. This polyclonal pool offers a heterogeneous loss-of-function model, eliminating endogenous catalase activity and enabling investigation of hydrogen peroxide metabolism and oxidative stress responses without clonal selection.
The 786-O cell line is a well-established clear cell renal cell carcinoma (ccRCC) model characterized by a homozygous VHL mutation (VHLM1). This mutation results in loss of functional von Hippel-Lindau protein and constitutive stabilization of hypoxia-inducible factors (HIFs), driving pseudohypoxic signalling and altering metabolic and redox homeostasis. Consequently, 786-O cells exhibit heightened sensitivity to oxidative insult, making them a pertinent host for studying antioxidant defence mechanisms.
Catalase is a heme-containing peroxisomal enzyme that catalyzes the decomposition of hydrogen peroxide (H?O?) into water and molecular oxygen, serving as a key cellular antioxidant. CAT expression is transcriptionally regulated by FOXO and PPAR signaling, and is induced under oxidative stress via NRF2 (NFE2L2) activation. Downstream, catalase activity protects cells from oxidative DNA damage, modulates redox-sensitive pathways including MAPK and NF-??B, and inhibits apoptosis. Catalase function is coordinated with interacting partners such as the peroxisomal import receptor PEX5, superoxide dismutase 1 (SOD1), and glutathione peroxidases, forming an integrated network for peroxide detoxification.
In the VHL-mutant 786-O background, CAT gene disruption exacerbates the inherent redox imbalance, leading to accumulation of endogenous H?O? and heightened oxidative stress. This model thus provides a powerful tool to dissect the dual roles of hydrogen peroxide in ccRCC pathophysiology??as a damaging agent promoting DNA lesions and apoptosis, and as a signaling molecule that can trigger adaptive survival responses through NRF2- and FOXO-dependent gene expression programs.
The CAT Knockout 786-O Polyclonal Cells are ideally suited for a broad range of applications, including probing oxidative stress responses, studying cancer cell redox adaptation, evaluating the impact of catalase loss on tumorigenesis, screening antioxidant compounds, and investigating mechanisms of chemoresistance. Representative assays include catalase activity measurements, ROS detection with H?DCFDA, ??H2AX staining for DNA damage, and flow cytometric analysis of apoptosis via Annexin V. For further information, please contact Ascent Research.
