Role for ionic fluxes on cell death and apoptotic volume decrease in cultured cerebellar granule neurons

Hernandez-Enriquez, Berenice; Arellano, Rogelio O.; Morán, Julio

doi:10.1016/j.neuroscience.2010.01.046

Cited by 15 publications

(26 citation statements)

References 56 publications

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“…7). This observation is consistent with significant reduction of mean volume in staurosporine-treated HeLa, U937 and NG108-15 cells measured by Coulter-type cell size analyzer [14,28] as well as decrease of single cell volume estimated from the cross-sectional area of cerebellar granule neurones [29] and by recently developed 3D reconstruction technique using negative transmission contrast rendered to T24 cells by strongly colored membrane-impermeable dye [30]. Third, decreased cell volume detected in cells undergoing apoptosis can be at least partially explained by secondary events, such as plasma membrane budding and the formation of apoptotic bodies rather than by primary shrinkage triggered by outwardly directed movements of intracellular osmolytes and osmotically obliged water.…”

Section: Discussionsupporting

confidence: 89%

Swelling rather than shrinkage precedes apoptosis in serum-deprived vascular smooth muscle cells

et al. 2012

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Contrasting cell volume behaviours (swelling vs. shrinkage) are considered as criteria to distinguish necrosis from apoptosis. In this study, we employed a time-lapse, dual-image surface reconstruction technique to assess the volume of single vascular smooth muscle cells transfected with E1A-adenoviral protein (E1A-VSMC) and undergoing rapid apoptosis in the absence of growth factors or in the presence of staurosporine. After 30- to 60-min lag-phase, serum-deprived E1A-VSMC volume was increased by ~40%, which preceded maximal increments of caspase-3 activity and chromatin cleavage. Swollen cells underwent rapid apoptotic collapse, documented by plasma membrane budding, and terminated in 10-15 min by the formation of numerous apoptotic bodies. Suppression of apoptosis by inhibition of Na(+),K(+)-ATPase and activation of cAMP signalling with ouabain and forskolin, respectively, completely abolished the swelling of serum-deprived E1A-VSMC. In contrast to serum deprivation, apoptotic collapse of staurosporine-treated E1A-VSMC preceded attenuation of their volume by ~30%. Neither transient hyposmotic swelling nor isosmtotic shrinkage triggered apoptosis. Our results show that cell shrinkage can not be considered as ubiquitous hallmark of apoptosis. The involvement of stimulus-specific cell volume perturbations in initiation and progression of apoptosis in vascular smooth muscle cells should be examined further.

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Section: Discussionsupporting

confidence: 89%

Swelling rather than shrinkage precedes apoptosis in serum-deprived vascular smooth muscle cells

et al. 2012

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“…This is in line with reports on other cell types (Bortner et al, 2001;Bortner and Cidlowski, 2003;Thompson et al, 2001). Even though volume decrease is a hallmark of apoptosis, several studies have shown that it is the increased ionic fluxes across the membrane that are important during apoptosis rather than the change in volume Hernández-Enríquez et al, 2010;Maeno et al, 2012).…”

Section: Discussionsupporting

confidence: 91%

The role of ion channels and intracellular metal ions in apoptosis of Xenopus oocytes

Englund¹

2014

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Apoptosis is one type of programmed cell death, important during tissue development and to maintain the tissue homeostasis. Apoptosis comprises a complex network of internal signaling pathways, and an important part of this signaling network is the action of voltage‐gated ion channels. The aim of this thesis was to explore the role of ion channels and the role of intracellular metal ions during apoptosis in Xenopus laevis oocytes. The reasons for using these oocytes are that they are large, robust, easy to handle, and easy to study electrophysiologically. Apoptosis was induced either chemically by incubation of the oocytes in staurosporine (STS) or mechanically by centrifugation of the oocytes. Ion currents were measured by a two‐electrode voltage clamp technique, intracellular ion concentrations were measured either directly by in‐house developed K+‐selective microelectrodes or indirectly by the electrophysiological technique, and apoptosis was measured by caspase‐3 activation. Paper I describes that the intracellular K+ concentration was reduced by about 30 % during STS‐induced apoptosis. However, this reduction was prevented by excessive expression of exogenous ion channels. Despite the magnitude of the intracellular K+ concentration, either normal or reduced level, the oocytes displayed normal signs of apoptosis, suggesting that the intracellular K+ reduction was not required for the apoptotic process. Because the intracellular K+ concentration was not critical for apoptosis we searched for other ion fluxes by exploring the electrophysiological properties of X. laevis oocytes. Paper II, describes a non‐inactivating Na+ current activated at positive membrane voltages that was upregulated by a factor of five during STS‐induced apoptosis. By preventing influx of Na+, the apoptotic signaling network involving capsase‐3 was prevented. To molecularly identify this voltage‐gated Na channel, the X. tropicalis genome and conserved regions of the human SCNA genes were used as a map. Paper III, shows that the voltage‐gated Na channel corresponds to the SCN2A gene ortholog and that supression of this SCN2A ortholog using miRNA prevented cell death. In conclusion, this thesis work demonstrated that a voltage‐gated Na channel is critical for the apoptotic process in X. laevis oocytes by increasing the intracellular Na+ concentration

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“…Thus, in Xenopus oocytes caspase-3 activation could possibly be triggered by an altered ionic strength mediated by ions other than K ϩ . Other studies show that STS-induced caspase-3 activation and apoptosis are not prevented by various K ϩ channel blockers in rat cortical neurons (30), rat cerebellar granule cells (31), mouse neuroblastoma cells (32), salmonid cells, and hepatocytes (33). Even though the intracellular K ϩ concentration was not monitored in these studies, the reported caspase-3 activity despite the use of K ϩ channel blockers suggests that further cell types have a K ϩ -independent mechanism for inducing apoptosis.…”

Section: Discussionmentioning

confidence: 95%

Intracellular K+ Concentration Decrease Is Not Obligatory for Apoptosis

Börjesson

Englund

Asif

et al. 2011

Journal of Biological Chemistry

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Role for ionic fluxes on cell death and apoptotic volume decrease in cultured cerebellar granule neurons

Cited by 15 publications

References 56 publications

Swelling rather than shrinkage precedes apoptosis in serum-deprived vascular smooth muscle cells

Swelling rather than shrinkage precedes apoptosis in serum-deprived vascular smooth muscle cells

The role of ion channels and intracellular metal ions in apoptosis of Xenopus oocytes

Intracellular K+ Concentration Decrease Is Not Obligatory for Apoptosis

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