Photo-Oxidative Disruption of Lysosomal Membranes Causes Apoptosis of Cultured Human Fibroblasts

Brunk, Ulf T.; Dalen, Helge; Roberg, Karin; Hellquist, Henrik

doi:10.1016/s0891-5849(97)00007-5

Cited by 264 publications

(221 citation statements)

References 20 publications

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“…11,50,[62][63][64][65][66] One mechanism by which cathepsins are postulated to directly contribute to cell death is by inducing lysosomal destabilization and enzyme leakage into cell cytoplasm. [67][68][69][70] This phenomenon has been described during oxidative stress in nonneuronal cells 71 and experimental brain ischemia in primates. 72 However, some recent studies have shown that activation of the lysosomes and/or lysosomal enzymes is also observed in the absence of cell death in animal models of neurodegenerative disorders.…”

Section: Loss Of Cholinergic Neurons and Ci-mpr 1149mentioning

confidence: 85%

Up-Regulation of Cation-Independent Mannose 6-Phosphate Receptor and Endosomal-Lysosomal Markers in Surviving Neurons after 192-IgG-Saporin Administrations into the Adult Rat Brain

Hawkes

Kabogo

Amritraj

et al. 2006

The American Journal of Pathology

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The cation-independent mannose 6-phosphate receptor (CI-MPR) is a single transmembrane domain glycoprotein that plays a major role in the trafficking of lysosomal enzymes from the trans-Golgi network to the endosomal-lysosomal (EL) system. Because dysfunction of EL system is associated with a variety of neurodegenerative disorders, it is possible that the CI-MPR may have a role in regulating neuronal viability after toxicity/injury. In the present study, we report that 192-IgG-saporin-induced loss of basal forebrain cholinergic neurons causes a transient upregulation of CI-MPR protein levels in surviving neurons of the basal forebrain and frontal cortex but not in the brainstem region, which was relatively spared by the immunotoxin. This was accompanied by a parallel time-dependent increase in other EL markers, ie, cathepsin D, Rab5, and LAMP2 in the basal forebrain region, whereas in the frontal cortex the levels of cathepsin D, and to some extent Rab5, were increased. Given the critical role of the EL system in the clearance of abnormal proteins in response to changing conditions, it is likely that the observed increase in the CI-MPR and components of the EL system in surviving neurons after 192-IgG-saporin treatment represents an adaptive mechanism to restore the metabolic/structural abnormalities induced by the loss of cholinergic neurons.

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Section: Loss Of Cholinergic Neurons and Ci-mpr 1149mentioning

confidence: 85%

Up-Regulation of Cation-Independent Mannose 6-Phosphate Receptor and Endosomal-Lysosomal Markers in Surviving Neurons after 192-IgG-Saporin Administrations into the Adult Rat Brain

Hawkes

Kabogo

Amritraj

et al. 2006

The American Journal of Pathology

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“…16,17 Pathways of lysosomal origin may lead to apoptosis associated with caspases while the release of lysosomal proteases, such as the cysteine cathepsins B and L and the aspartyl cathepsin D, may cause necrosis, apoptosisor necrosis-like cell death. 18,19 Calpains, cytosolic calcium-activated neutral cysteine proteases, are, at least in part, also associated with lysosomes. 19,20 Under appropriate stimuli, their active form dissociates from its inhibitor, calpastatin, and translocates to the cytoplasmic membrane where cytoskeletal attachments would be cleaved.…”

Section: Introductionmentioning

confidence: 99%

“…18,19 Calpains, cytosolic calcium-activated neutral cysteine proteases, are, at least in part, also associated with lysosomes. 19,20 Under appropriate stimuli, their active form dissociates from its inhibitor, calpastatin, and translocates to the cytoplasmic membrane where cytoskeletal attachments would be cleaved. 21 Active calpains participate in the regulation of both apoptosis and necrosis.…”

Section: Introductionmentioning

confidence: 99%

Caspase-independent pathways of hair cell death induced by kanamycin in vivo

et al. 2005

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Cochlear and vestibular sensory cells undergo apoptosis when exposed to aminoglycoside antibiotics in organ culture, but mechanisms of chronic drug-induced hair cell loss in vivo are unclear. We investigated cell death pathways in a mouse model of progressive kanamycin-induced hair cell loss. Hair cell nuclei showed both apoptotic-and necrotic-like appearances but markers for classic apoptotic pathways (cytochrome c, caspase-9, caspase-3, JNK, TUNEL) were absent. In contrast, drug treatment caused EndoG translocation, activation of l-calpain, and both the synthesis and activation of cathepsin D. Poly (ADP-ribose) polymerase 1 (PARP1) was decreased, but a caspase-derived 89 kDa PARP1 fragment was not present. The mRNA level of PARP1 remained unchanged. Thus, chronic administration of aminoglycosides causes multiple forms of cell death, without a major contribution by classic apoptosis. These results provide a better understanding of the toxic effects of aminoglycosides and are relevant to design protection from aminoglycosideinduced hearing loss.

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“…Obvious lysosomal breach at later stages of cell death led to overlooking the active participation of lysosomes in the process of cell death. A series of studies have shown the destabilization of the lysosomal membrane to be an early event in cellular devitalization [18,28 -30], and more recently, to be a reliable preceding event of apoptosis caused by oxidative stress, Fas activation, and growth factor deprivation [19,[31][32][33][34][35][36][37][38][39][40]. In the present study, the acridine orange relocation developed within 15 min of exposure to a lethal dose of naphthazarin, and the subsequent decreased mitochondrial potential did not appear until 2 h after exposure.…”

Section: Discussionmentioning

confidence: 99%

Imidazoline drugs stabilize lysosomes and inhibit oxidative cytotoxicity in astrocytes

Choi

Lee

et al. 2002

Free Radical Biology and Medicine

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Photo-Oxidative Disruption of Lysosomal Membranes Causes Apoptosis of Cultured Human Fibroblasts

Cited by 264 publications

References 20 publications

Up-Regulation of Cation-Independent Mannose 6-Phosphate Receptor and Endosomal-Lysosomal Markers in Surviving Neurons after 192-IgG-Saporin Administrations into the Adult Rat Brain

Up-Regulation of Cation-Independent Mannose 6-Phosphate Receptor and Endosomal-Lysosomal Markers in Surviving Neurons after 192-IgG-Saporin Administrations into the Adult Rat Brain

Caspase-independent pathways of hair cell death induced by kanamycin in vivo

Imidazoline drugs stabilize lysosomes and inhibit oxidative cytotoxicity in astrocytes

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