Induction of carbonic anhydrase IX by hypoxia and chemical disruption of oxygen sensing in rat fibroblasts and cardiomyocytes

CA IX is an active transmembrane carbonic anhydrase isoform functionally implicated in cell adhesion and pH control. Human CA IX is strongly induced by hypoxia and frequently associated with various tumors. In this study, we investigated the expression of the rat CA IX in response to chronic hypoxia and to treatment with chemical compounds that disrupt oxygen sensing, including dimethyloxalylglycine, dimethylester succinate, diazoxide, and tempol. We brought the evidence that expression of CA IX is regulated by hypoxia and hypoxia-mimicking compounds in immortalized Rat2 fibroblasts and BP6 rat fibrosarcoma cells in a cell-type-specific manner. We also demonstrated, for the first time, that CA IX is expressed in hypoxic primary rat cardiomyocytes and in immortalized H9c2 cardiomyocytes exposed to physiological or chemical hypoxia and that CA IX expression is increased in hypoxic rat tissues in vivo. Our findings suggest that CA IX expression is not limited to cancer but may be also induced in other pathological situations associated with ischemia or metabolic disturbances leading to activation of the HIF pathway. These data support the view that rats can represent useful model for studies of CA IX as a component of endogenous protection mechanisms associated with hypoxia or perturbed oxygen sensing.