Targeting of carbonic anhydrase IV to plasma membranes is altered in cultured human pancreatic duct cells expressing a mutated (ΔF508) CFTR

Chemical chaperones protect from effects of apoptosis-inducing mutation in carbonic anhydrase IV identified in retinitis pigmentosa 17

“…The synthesis and secretion of each protein was reduced compared with that seen when wild-type CA IV cDNA was cotransfected with the respective cDNA. Similar results have been reported for a mutant growth hormone, which reduced the synthesis and secretion of other proteins (36), and for ⌬508CFTR, the mutant cystic fibrosis protein (37), which reduced production of expressed CA IV. We demonstrate here that both specific and nonspecific chemical chaperones overcame the negative trans effect of R14W CA IV expression on production of the other secretory proteins.…”

“…Trans effects of expression of unfolded proteins on the production of other secretory or membrane proteins have been reported by others (36,37). To test whether expressing the R14W CA IV has such an effect in transfected COS-7 cells, we compared R14W CA IV and wild-type CA IV for effects on the expression of two other secretory proteins expressed from cotransfecting plasmids.…”

Elevated hepatic SULT1E1 activity in mouse models of cystic fibrosis alters the regulation of estrogen responsive proteins

“…Both CA and GST-P1 are estrogen-responsive proteins that play important roles in defense against oxidative stress and toxic compounds involved in aging and the pathogenesis of many diseases [33,34]. In pancreatic duct cells which express CFTR-DF508, the intracellular trafficking of CA is impaired [35], and E2 modulates CA expression in male mouse efferent renal ductules via ERa [36]. GST-P1 is involved in detoxification reactions and also has a protective role against oxidative stress.…”

Breath sulfides and pulmonary function in cystic fibrosis

“…Investigators have questioned whether the distribution and͞or activity of carbonic anhydrase, which is found throughout the human body, may be altered in CF patients (27,28). Recently, Fanjul et al (29) showed that the targeting of the carbonic anhydrase isoform CA IV to plasma membranes in human pancreatic duct cells, which expressed the ⌬F508 CFTR mutation, is disrupted. Thus, an intriguing explanation of the OCS data might be that a functional impairment in carbonic anhydrase may limit OCS uptake and metabolism in CF patients' lungs, contributing, along with bacterial production of the gas, to generally higher levels within the alveolar and or airway gas.…”