6-Hydroxydopamine induces cystatin C-mediated cysteine protease suppression and cathepsin D activation

Lee, Daniel; Womble, Tracy; Mason, Ceceile W.; Jackson, Inneke M.; Lamango, Nazarius S.; Severs, Walter B.; Palm, Donald E.

doi:10.1016/j.neuint.2006.12.006

Cited by 23 publications

(19 citation statements)

References 53 publications

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“…Also, enhanced CYSC expression has been identified in vitro following 6-hydroxydopamine exposure [28,29]. The exact role of CYSC following injury remains highly controversial.…”

Section: Discussionmentioning

confidence: 99%

“…Changes in mRNA and protein expression of CYSC have been associated with oxidative stress [26]. Furthermore, changes in CYSC expression have been seen in various models of neuronal injuries such as PD [27][28][29], AD [30,31], ALS [32,33], heritable cerebral hemorrhage with amyloidosis of the Icelandic type angiopathy (HCHWA-I) [34], and transient forebrain ischemia [35]. However, the significance between the association of CYSC with CATB and CATD in neurodegenerative disorders and neuronal injury remains unknown.…”

Section: Introductionmentioning

confidence: 99%

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Hydrogen Peroxide Induces Lysosomal Protease Alterations in PC12 Cells

et al. 2007

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Alterations in lysosomal proteases have been implicated in many neurodegenerative diseases. The current study demonstrates a concentration-dependent decrease in PC12 cell viability and transient changes in cystatin C (CYSC), cathepsin B (CATB), cathepsin D (CATD) and caspase-3 following exposure to H2O2. Furthermore, activation of CATD occurred following exposure to H2O2 and cysteine protease suppression, while inhibition of CATD with pepstatin A significantly improved cell viability. Additionally, significant PARP cleavage, suggestive of caspase-3-like activity, was observed following H2O2 exposure, while inhibition of caspase-3 significantly increased cell viability compared to H2O2 administration alone. Collectively, our data suggest that H2O2 induced cell death is regulated at least in part by caspase-3 and CATD. Furthermore, cysteine protease suppression increases CATD expression and activity. These studies provide insight for alternate pathways and potential therapeutic targets of cell death associated with oxidative stress and lysosomal protease alterations.

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“…Also, enhanced CYSC expression has been identified in vitro following 6-hydroxydopamine exposure [28,29]. The exact role of CYSC following injury remains highly controversial.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hydrogen Peroxide Induces Lysosomal Protease Alterations in PC12 Cells

et al. 2007

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“…Cathepsins in the lysosomes were activated and then translocated to the cytosol during apoptosis induced by oxidative stress [12,13]. Therefore, our study also aimed to evaluate apoptotic cell death caused by lysosomes isolated from HeLa cells subjected to oxidative stress.…”

Section: Oxidative Stress Increased In Vitro Lysosomal Function In Hementioning

confidence: 99%

“…Alteration of both lysosomal cysteine and aspartic proteases has been observed following oxidative stress-induced apoptosis [12], suggesting that lysosomal enzyme mediation is a key factor in inducing apoptotic cell death. A complete breakdown of the lysosomes with the release of high concentrations of lysosomal enzymes into the cytosol results in unregulated cell death when exposed to severe oxidative stresses [13]. If lysosome disruption was caused by oxidative stress, it would be impossible to evaluate in vitro lysosomal function as a cell organelle.…”

Section: Introductionmentioning

confidence: 99%

Increased In Vitro Lysosomal Function in Oxidative Stress-Induced Cell Lines

Yoon

Bang

Park

et al. 2010

Appl Biochem Biotechnol

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Exposure of mammalian cells to oxidative stress alters lysosomal enzymes. Through cytochemical analysis of lysosomes with LysoTracker, we demonstrated that the number and fluorescent intensity of lysosome-like organelles in HeLa cells increased with exposure to hydrogen peroxide (H₂O₂), 6-hydroxydopamine (6-OHDA), and UVB irradiation. The lysosomes isolated from HeLa cells exposed to three oxidative stressors showed the enhanced antimicrobial activity against Escherichia coli. Further, when lysosomes that were isolated from HeLa cells exposed by oxidative stress were treated to normal HeLa cells, the viability of the HeLa cells was drastically reduced, suggesting increased in vitro lysosomal function (i.e., antimicrobial activity, apoptotic cell death). In addition, we also found that cathepsin B and D were implicated in increased in vitro lysosomal function when isolated from HeLa cells exposed by oxidative stress. Decrease in cathepsin B activity and increase in cathepsin D activity were observed in lysosomes isolated from HeLa cells after treatment with H₂O₂, 6-ODHA, or UVB, but cathepsin B and D were not the sole factors to induce cell death by in vitro lysosomal function. Therefore, these studies suggest a new approach to use lysosomes as antimicrobial agents and as new materials for treating cancer cell lines.

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“…Cathepsin D is a lysosomal endoproteolytic aspartic proteinase, which plays an important role in lysosome [1]. Lysosome is a membrane-bound cytoplasmic organelle that serves as a major degradative compartment in eukaryotic cells [2].…”

Section: Introductionmentioning

confidence: 99%