Lactacystin-induced apoptosis of cultured mouse cortical neurons is associated with accumulation of PTEN in the detergent-resistant membrane fraction

Cheung, Nam Sang; Choy, M.S.; Halliwell, Barry; Teo, Tian Seng; Bay, Boon‐Huat; Lee, Alan Yiu Wah; Qi, Robert Z.; Koh, Vivien; Whiteman, Matthew; Koay, Evelyn Siew Chuan; Chiu, Lily; Zhu, Hong; Wong, Kim Ping; Beart, Philip M; Cheng, Heung‐Chin

doi:10.1007/s00018-004-4127-7

Cited by 30 publications

(28 citation statements)

References 19 publications

(17 reference statements)

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“…Notably, these inhibitors are selective for calpains and do not target the proteasome, another major proteolytic pathway in cells. In fact, proteasome inhibitors themselves are quite toxic and rapidly trigger activation of caspase-3 and apoptosis in GCs (78 -80) 3 and in other cultured neurons (81)(82)(83)(84).…”

Section: Discussionmentioning

confidence: 99%

Nuclear Calpain Regulates Ca2+-dependent Signaling via Proteolysis of Nuclear Ca2+/Calmodulin-dependent Protein Kinase Type IV in Cultured Neurons

Tremper-Wells

Vallano

2005

Journal of Biological Chemistry

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CaMKIV is highly enriched in the nucleus and thought to be critical for improved survival. Here, we demonstrate by immunolocalization/ confocal microscopy and subcellular fractionation that the regulatory and catalytic subunits of m-calpain are enriched in GC nuclei, including GCs grown in medium containing 5 mM KCl. Calpain-mediated proteolysis of CaMKIV is selective, as several other nuclear and nonnuclear calpain substrates were not degraded under chronic depolarizing culture conditions. Depolarization and Ca 2؉ -dependent down-regulation of CaMKIV were associated with significant alterations in other components of the Ca 2؉ -CaMKIV signaling cascade: the ratio of phosphorylated to total cAMP response element-binding protein (a downstream CaMKIV substrate) was reduced by ϳ10-fold, and the amount of CaMK kinase (an upstream activator of CaMKIV) protein and mRNA was significantly reduced. We hypothesize that calpain-mediated CaMKIV proteolysis is an autoregulatory feedback response to sustained activation of a Ca 2؉ -CaMKIV signaling pathway, resulting from growth of cultures in medium containing 25 mM KCl. This study establishes nuclear m-calpain as a regulator of CaMKIV and associated signaling molecules under conditions of sustained Ca 2؉ influx.

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Section: Discussionmentioning

confidence: 99%

Nuclear Calpain Regulates Ca2+-dependent Signaling via Proteolysis of Nuclear Ca2+/Calmodulin-dependent Protein Kinase Type IV in Cultured Neurons

Tremper-Wells

Vallano

2005

Journal of Biological Chemistry

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“…Fornai and colleagues (7) and Rideout and coworkers (8) documented that proteasome inhibition can induce apoptosis in DA neurons, whereas Rideout and colleagues (25) and Cheung and coworkers (26) reported that lactacystin activated caspase-3 in cortical neurons, cerebella granule neurons, and sympathetic neurons. Our study provided direct evidence showing that caspase-3 was activated in DA neurons in response to proteasome inhibition.…”

Section: Discussionmentioning

confidence: 99%

One Year of Caloric Restriction in Humans: Feasibility and Effects on Body Composition and Abdominal Adipose Tissue

Racette¹,

Weiss²,

Villareal³

et al. 2006

The Journals of Gerontology: Series A

209

187

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Evidence has shown that ubiquitin proteasome system (UPS) impairment plays an important role in the dopamine (DA) neurodegeneration in Parkinson's disease (PD). It has been reported that application of proteasomal inhibitor lactacystin in ventral mesencephalon (VM) cultures can cause DA neurodegeneration, although the underlying mechanisms are not clear. Herein, we used the lactacystin-induced DA cell degeneration model to study the neuroprotection of glial cellderived neurotrophic factor (GDNF) in VM cultures. We measured the expression of endoplasmic reticulum stress (ERS)-related genes, and determined the caspase-3 activation, apoptotic cell death, as well as a-synuclein-positive inclusions in DA neurons. We found that GDNF treatment significantly suppressed the expression of ERS-related genes and inhibited the activation of caspase-3 and apoptotic cell death without affecting a-synuclein-positive inclusions in DA neurons. Our study suggests that the protection of GDNF against DA neurodegeneration in the UPS impairment model is associated with ERS and caspase-3 suppression.

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“…21,124 In cortical neurons of the central nervous system, Jessica et al 125 analyzed the expression of different AQPs while cells undergo apoptosis induced by treatment with lactacystin, a specific proteasome inhibitor. [126][127][128] These authors found that AQP4 was highly downregulated, suggesting that this aquaporin, considered to be the main water channel in the brain, 129 does not play an important role in the loss of water during AVD. In contrast, overexpression of AQP1, AQP8 and AQP9 was observed after lactacystin treatment.…”

Section: Apoptosis and Aqpsmentioning

confidence: 99%

“…In contrast, overexpression of AQP1, AQP8 and AQP9 was observed after lactacystin treatment. [126][127][128] However, favoring a role for AQP4 in apoptosis, Kong et al 87 observed increased basal apoptosis in adult neural stem cells obtained from KO AQP4 ¡/¡ mice.…”

Section: Apoptosis and Aqpsmentioning

confidence: 99%

Role of aquaporins in cell proliferation: What else beyond water permeability?

2016

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In addition to the extensive data demonstrating the importance of mammalian AQPs for the movement of water and some small solutes across the cell membrane, there is now a growing body of evidence indicating the involvement of these proteins in numerous cellular processes seemingly unrelated, at least some of them in a direct way, to their canonical function of water permeation. Here, we have presented a broad range of evidence demonstrating that these proteins have a role in cell proliferation by various different mechanisms, namely, by allowing fast cell volume regulation during cell division; by affecting progression of cell cycle and helping maintain the balance between proliferation and apoptosis, and by crosstalk with other cell membrane proteins or transcription factors that, in turn, modulate progression of the cell cycle or regulate biosynthesis pathways of cell structural components. In the end, however, after discussing all these data that strongly support a role for AQPs in the cell proliferation process, it remains impossible to conclude that all these other functions attributed to AQPs occur completely independently of their water permeability, and there is a need for new experiments designed specifically to address this interesting issue.

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Lactacystin-induced apoptosis of cultured mouse cortical neurons is associated with accumulation of PTEN in the detergent-resistant membrane fraction

Cited by 30 publications

References 19 publications

Nuclear Calpain Regulates Ca2+-dependent Signaling via Proteolysis of Nuclear Ca2+/Calmodulin-dependent Protein Kinase Type IV in Cultured Neurons

Nuclear Calpain Regulates Ca2+-dependent Signaling via Proteolysis of Nuclear Ca2+/Calmodulin-dependent Protein Kinase Type IV in Cultured Neurons

One Year of Caloric Restriction in Humans: Feasibility and Effects on Body Composition and Abdominal Adipose Tissue

Role of aquaporins in cell proliferation: What else beyond water permeability?

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