Rupture of rat liver lysosomes mediated by l-amino acid esters

Goldman, Rachel; Kaplan, Arnold

doi:10.1016/0005-2736(73)90114-4

Cited by 109 publications

(50 citation statements)

References 13 publications

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“…However, Goldman and Kaplan ( 11) and Reeves (12) dem-onstrated that isolated lysosomes could be loaded with amino acids using the permeable methyl ester derivative. Intralysosomal esterases cleave the methyl ester leaving the less permeable amino acid in a high concentration.…”

Section: Introductionmentioning

confidence: 99%

Intracellular cystine loading inhibits transport in the rabbit proximal convoluted tubule.

Salmon¹,

Baum

1990

J. Clin. Invest.

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Cystinosis is an autosomal recessive disorder characterized by a high intracellular cystine concentration. To establish an in vitro model of this disorder and examine the mechanism of the proximal tubule transport defect seen with elevated intracellular cystine concentrations, rabbit proximal convoluted tubules (PCT) were perfused in vitro. PCTs were loaded with cystine using cystine dimethyl ester, a permeative methyl ester derivative. Bath cystine dimethyl ester (0.5 mM) reduced volume absorption (JV) (0.67±0.07 to 0.15±0.09 nl/mm min, P < 0.01), bicarbonate transport (JTcO2) (47.2±4.9 to 11.1±2.8 pmol/mm * min, P < 0.001) and glucose transport (JGLU) (34.1±1.5 to 19.7±1.5 pmol/mm -min, P < 0.001). The methyl esters of leucine (0.5 mM), and tryptophan (0.5 and 2.0 mM) had no effect on these parameters. To examine if intracellular reduction of cystine to cysteine could contribute to the inhibition in transport, the effect of bath cysteine methyl ester on proximal tubular transport was examined. Bath cysteine methyl ester (2 but not 0.5 mM) resulted in an inhibition in JV, JGLU, and JTCO2. Cystine dimethyl ester had no effect on mannitol or bicarbonate permeability. These data are consistent with intracellular proximal tubular cystine accumulation resulting in an inhibition of active transport. (J. Clin. Invest. 1990. 85:340-344.) cystinosis * cystine dimethyl ester * Fanconi syndrome

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Section: Introductionmentioning

confidence: 99%

Intracellular cystine loading inhibits transport in the rabbit proximal convoluted tubule.

Salmon¹,

Baum

1990

J. Clin. Invest.

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“…This issue was solved with the introduction of dimethyl esters of amino acids, which readily passed the lysosomal membrane and, once inside the organelle, were rapidly degraded by lysosomal hydrolases to yield free amino acid and methanol thus allowing amino acid loading of the lysosomes (6,7). CDME loading of intact leukocytes, cultured lymphoblasts, and fibroblasts established defective cystine exodus from the lysosomes as basic defect in cystinosis (8 -10).…”

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confidence: 99%

Decreased Intracellular ATP Content and Intact Mitochondrial Energy Generating Capacity in Human Cystinotic Fibroblasts

et al. 2006

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ABSTRACT:Cystinosis is an autosomal recessive lysosomal storage disorder caused by a defect in the lysosomal cystine carrier cystinosin. Cystinosis is the most common cause of inherited Fanconi syndrome leading to renal failure, in which the pathogenesis is still enigmatic. Based on studies of proximal tubules loaded with cystine dimethyl ester (CDME), altered mitochondrial adenosine triphosphate (ATP) production was proposed to be an underlying pathologic mechanism. Thus far, however, experimental evidence supporting this hypothesis in humans is lacking. In this study, energy metabolism was extensively investigated in primary fibroblasts derived from eight healthy subjects and eight patients with cystinosis. Patient's fibroblasts accumulated marked amounts of cystine and displayed a significant decrease in intracellular ATP content. Remarkably, overall energy-generating capacity, activity of respiratory chain complexes, ouabain-dependent rubidium uptake reflecting Na,K-ATPase activity, and bradykinin-stimulated mitochondrial ATP production were all normal in these cells. In conclusion, the data presented demonstrate that mitochondrial energy-generating capacity and Na,K-ATPase activity are intact in cultured cystinotic fibroblasts, thus questioning the idea of altered mitochondrial ATP synthesis as a keystone for the pathogenesis of cystinosis.

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“…Lysosomal DCP was partially purified from rat liver as follows: Lysozome-enriched fractions [5] from homogenates of rat liver were homogenized in presence of 0.1% Triton X-IO0 in 0.5 M phosphate buffer (pH 6.5) containing EDTA (6.0 raM) and cysteine (3.0 mg/ml). Acetone precipitation (0.9 ml acetone/1.0 ml extract) resulted in an 18-fold increase in specific activity.…”

Section: Methodsmentioning

confidence: 99%

Use of an intramolecularly quenched flourogenic substrate for study of a thiol‐dependent acidic dipeptidyl carboxypeptidase in cellular extracts and in living cells

1981

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Rupture of rat liver lysosomes mediated by l-amino acid esters

Cited by 109 publications

References 13 publications

Intracellular cystine loading inhibits transport in the rabbit proximal convoluted tubule.

Intracellular cystine loading inhibits transport in the rabbit proximal convoluted tubule.

Decreased Intracellular ATP Content and Intact Mitochondrial Energy Generating Capacity in Human Cystinotic Fibroblasts

Use of an intramolecularly quenched flourogenic substrate for study of a thiol‐dependent acidic dipeptidyl carboxypeptidase in cellular extracts and in living cells

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