765 Amino Acid Efflux From Normal and Cystinotic Leukocyte Lysosomes

Steinherz, R; Tietze, Frank; Raiford, David S.; Schulman, J D

doi:10.1203/00006450-198104001-00789

Cited by 15 publications

(19 citation statements)

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“…Examination by Steinherz et al (20) of isolated leukocyte lysosomes loaded with cystine dimethyl ester yielded results similar to those reported here. In this preliminary work, cystine efflux was very prolonged compared to the efflux ofother amino acids and did not differ between normal and-cystinotic leukocyte lysosomes.…”

Section: Resultssupporting

confidence: 90%

“…These cells showed no significant change in cystine content for 90 min when placed in cystine-free medium. Cystinotic fibroblasts exposed to 30 mM CSSG for 24 hr had very much increased cystine levels (approximately 20 teresting. One possible conclusion is that, under normal circumstances, cystine or a metabolite of cystine rapidly exits the lysosome.…”

Section: Resultsmentioning

confidence: 99%

“…The cystine content ofheterozygous leukocytes, on the other hand, is 4-5 times greater than that ofnormal leukocytes (2). Steinherzet al (19) have used cystine dimethyl ester to load human leukocytes with cystine. The patterns of cystine loss by normal and cystinotic cells were similar to those reported here.…”

Section: Resultsmentioning

confidence: 99%

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Cystine accumulation and loss in normal, heterozygous, and cystinotic fibroblasts.

Jonas¹,

Greene²,

Smith³

et al. 1982

Proc. Natl. Acad. Sci. U.S.A.

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Section: Resultssupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

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Cystine accumulation and loss in normal, heterozygous, and cystinotic fibroblasts.

Jonas¹,

Greene²,

Smith³

et al. 1982

Proc. Natl. Acad. Sci. U.S.A.

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“…PKC␦ is not labeled when TNF-␣ is absent (Figure 4, lanes 1 and 5), indicating that apoptosis induction and lysosomal permeabilization are required for labeling, but PKC␦ is labeled with 35 S-cystine after TNF-␣ exposure. It is well established that amino acid methylesters are lysosomotropic and that CDME treatment causes accumulation of cystine in the lysosome (23,27). Labeling of the lysosomal pool of cystine with 35 S-CDME and the subsequent demonstration of PKC␦ labeling from that pool demonstrate that PKC␦ is cysteinylated by lysosomal cystine after apoptosis is induced by TNF-␣ in cultured cells.…”

Section: Resultsmentioning

confidence: 97%

“…They were synthesized using the method of Steinherz et al (23,24). Samples were analyzed by thin-layer chromatography to assess completeness of esterification (data not shown).…”

Section: Methylester Synthesismentioning

confidence: 99%

Increased Apoptosis in Cystinotic Fibroblasts and Renal Proximal Tubule Epithelial Cells Results from Cysteinylation of Protein Kinase Cδ

Park¹,

Pejovic²,

Kerisit³

et al. 2006

Journal of the American Society of Nephrology

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Cystinosis is a rare genetic disease characterized by defective lysosomal cystine transport and increased lysosomal cystine. How lysosomal cystine causes the lethal nephropathic phenotype is unknown. It was shown recently that cultured fibroblasts and renal proximal tubule epithelial cells whose lysosomes are cystine-loaded display a two-fold or greater increase in apoptosis after both intrinsic and extrinsic stimuli. The mechanism for the increased apoptosis is unknown. Protein kinase C␦ (PKC␦) is a proapoptotic protein kinase that has been shown in vitro to be activated via cysteinylation. This report now shows that PKC␦ forms disulfide bonds specifically with cystine that is released from lysosomes in cultured fibroblasts and renal proximal tubule epithelial cells during apoptosis. PKC␦ in cystinotic fibroblasts and renal proximal tubule epithelial cells have a four-to six-fold greater association with its substrate, lamin B, and a 2.5-fold increase in specific activity after TNF-␣ exposure. Both RNA inhibition and chemical inhibition of PKC␦ resulted in a significant decrease in apoptosis in cystinotic cells but not in normal cells. It is proposed that abnormally increased apoptosis plays a role in evolution of the cystinotic phenotype.

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Phosphorylase kinase in leukocytes and erythrocytes of a patient with glycogen storage disease type IX

Bashan

Potashnik

Ehrlich

et al. 1986

J of Inher Metab Disea

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765 Amino Acid Efflux From Normal and Cystinotic Leukocyte Lysosomes

Cited by 15 publications

References 0 publications

Cystine accumulation and loss in normal, heterozygous, and cystinotic fibroblasts.

Cystine accumulation and loss in normal, heterozygous, and cystinotic fibroblasts.

Increased Apoptosis in Cystinotic Fibroblasts and Renal Proximal Tubule Epithelial Cells Results from Cysteinylation of Protein Kinase Cδ

Phosphorylase kinase in leukocytes and erythrocytes of a patient with glycogen storage disease type IX

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