The calcium hypothesis of Cystic Fibrosis

Katz, Sidney A.; Schöni, Martin H.; Bridges, Michael A.

doi:10.1016/0143-4160(84)90021-6

Cited by 31 publications

(14 citation statements)

References 89 publications

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“…Exten sive, although not unequivocally consistent and reproducible, evidence has been pre sented in the last 10 years on derangement of calcium homeostasis in CF cells [13]. This also involved calcium uptake by isolated mi tochondria which was reported to be en hanced by different groups of investigators [14,15].…”

Section: Isolations Of Mitochondria From Mononuclear White Blood Cellsmentioning

confidence: 99%

The K(m) of NADH Dehydrogenase Is Decreased in Mitochondria of Cystic Fibrosis Cells

Dechecchi¹,

Girella²,

Cabrini³

et al. 1988

Enzyme

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The kinetic properties of the NADH dehydrogenase of the mitochondrial respiratory chain, assayed as NADH-dependent rotenone-sensitive cytochrome c reductase have been studied in mitochondria isolated from mononuclear white blood cells in patients affected by cystic fibrosis. Data reported here show that the apparent Km of the enzyme for NADH is significantly decreased in cystic fibrosis mitochondria. These findings are independent of the age or the clinical state of the disease and have also been obtained with mitochondria isolated from cultured skin fibroblasts. These observations support the notion that cystic fibrosis is possibly accompanied by alterations of intracellular membranes and these are evident also in circulating cells and cultured fibroblasts.

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Section: Isolations Of Mitochondria From Mononuclear White Blood Cellsmentioning

confidence: 99%

The K(m) of NADH Dehydrogenase Is Decreased in Mitochondria of Cystic Fibrosis Cells

Dechecchi¹,

Girella²,

Cabrini³

et al. 1988

Enzyme

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“…A number of investigators have suggested that a defect in cellular calcium homeostasis may be the etiologic principle, or at least may constitute an important element in the pathogenesis, of CF (2). Work in our laboratory (3)(4)(5)(6)(7) and that performed by a number of other independent investigators (8-1 3) has indicated that the transport and hydrolytic activity of plasma membranebound Ca2+-ATPase of erythrocytes and fibroblasts appears to be deficient in CF.…”

Section: Discussionmentioning

confidence: 93%

“…Work in our laboratory (3)(4)(5)(6)(7) and that performed by a number of other independent investigators (8-1 3) has indicated that the transport and hydrolytic activity of plasma membranebound Ca2+-ATPase of erythrocytes and fibroblasts appears to be deficient in CF. If a similar deficiency is found to occur in CF exocrine cells, this may explain a number of aspects of secretory and respiratory pathophysiology found to occur in this disorder (2). The possibility that plasma membrane-bound Ca2+-ATPase could represent the defective gene product in CF suggests the importance of physical and enzymologic characterization of CF and age/sex-matched control Ca2'-ATPase purified from calmodulin depleted erythrocyte membranes.…”

Section: Discussionmentioning

confidence: 99%

“…The exact relationship between these observations and the tively; ha2+ = 0.328 +-0.046 pmolar free calcium and evidence for disturbances in cellular calcium homeostasis, partic-0.333 + 0.040 for C F and control enzyme, respectively. ularly in exocrine glands, remains to be elucidated (2).…”

mentioning

confidence: 99%

“…20 mM Tris-CI, PH 7.4, and centrifuged at 2500 x I: to remove However, it is unclear at prescnt whether the cellular disturbance plasma and the huffy coat. Washed erythrocytes were then lysed in calcium handling is the primary defect of CF (2 (14,16). Calmodulin-deficient erythrocyte membranes (20-30 mg) were centrifuged at 100,000 x g a t 4" C for 5 min, and the pellet was solubilized at 4" C for 10 rnin at a protein concentration of 5 mg/ml in a solubilization solution somewhat similar to that used by Graf et a/.…”

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Isolation and Characterization of Erythrocyte Membrane Ca2+-ATPase in Cystic Fibrosis

Bridges

Katz

1986

Pediatr Res

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A B S T R A a . Ca2+-ATPase was purified from erythrocyte Work performed in our laboratory (3-7), as well as studies membranes prepared from cystic fibrosis (CF) blood Sam-conducted by other investigators (8-1 3), indicated that the activples (n = 10) and from ageisex-matched control blood ity of the calcium-transporting ATPase enzyme (Ca2+-ATPase) samples (n = 10). The kinetics of calcium activation of the of CF erythrocyte and fibroblast plasma membranes is deficient.purified enzyme was investigated in the presence of asolec-We found that the maximal calcium activation (VCa2+) of 45Ca2+-tin phospholipids and found to be virtually identical for transport and ATP hydrolysis of CF membranes is approximately both C F and control preparations: VC2+ = 3.01 + 0.24 50% of control levels. However, the affinity of these processes pmol ATP hydrolyzedimg pure enzymeimin (mean 2 SE) for calcium ion (I/Kd) is similar in CF and control membranes and 3.09 + 0.20 for C F and control Ca2+-ATPase, respec-(3-7). The exact relationship between these observations and the tively; ha2+ = 0.328 +-0.046 pmolar free calcium and evidence for disturbances in cellular calcium homeostasis, partic-0.333 + 0.040 for C F and control enzyme, respectively. ularly in exocrine glands, remains to be elucidated (2).The preparative procedure used (one-step purification byTo determine whether this Ca2+-ATPase deficiency reflects the calmodulin-affinity chromatography) allowed quantitative basic CF defect necessitates the characterization of the enzyme recovery of essentially 100% of the Ca2+-ATPase present in purified form. The present report presents data on the partial in detergent-solubilized erythrocyte membranes, enabling characterization of purified CF Ca2+-ATPase. A preliminary expression of the yield of purified enzyme in terms of the report of this work has been presented (29). quantity of starting membrane protein: 0.127% 2 0.006%

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Calcium Fluxes in Pathologically Altered Red Cells

Scharff¹,

Foder²

1989

The Red Cell Membrane

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The calcium hypothesis of Cystic Fibrosis

Cited by 31 publications

References 89 publications

The K(m) of NADH Dehydrogenase Is Decreased in Mitochondria of Cystic Fibrosis Cells

The K(m) of NADH Dehydrogenase Is Decreased in Mitochondria of Cystic Fibrosis Cells

Isolation and Characterization of Erythrocyte Membrane Ca2+-ATPase in Cystic Fibrosis

Calcium Fluxes in Pathologically Altered Red Cells

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