Caspase-3 activation induced by inhibition of mitochondrial complex I is facilitated by glycogen synthase kinase-3β and attenuated by lithium

King, Taj D.; Bijur, Gautam N.; Jope, Richard S.

doi:10.1016/s0006-8993(01)03005-0

Cited by 174 publications

(144 citation statements)

References 56 publications

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“…In accordance with our recent report that characterized rotenone-induced caspase-3-mediated apoptosis in SH-SY5Y cells (42), there was a nearly 6-fold increase in caspase-3 activity after treatment with 5 M rotenone (Fig. 4A).…”

Section: Stimulation Of Muscarinic Receptors Protects Against Rotenonsupporting

confidence: 93%

Muscarinic Receptor Activation Protects Cells from Apoptotic Effects of DNA Damage, Oxidative Stress, and Mitochondrial Inhibition

Sarno

Shestopal

King

et al. 2003

Journal of Biological Chemistry

107

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The impact of muscarinic receptor stimulation was examined on apoptotic signaling induced by DNA damage, oxidative stress, and mitochondrial impairment. Exposure of human neuroblastoma SH-SY5Y cells to the DNA-damaging agent camptothecin increased p53 levels, activated caspase-3, and caused cell death. Pretreatment with oxotremorine-M, a selective agonist of muscarinic receptors that are expressed endogenously in these cells, did not affect the accumulation of p53 but greatly attenuated caspase-3 activation and protected from cell death to nearly the same extent as treatment with a general caspase inhibitor. Treatment with 50 -200 M H 2 O 2 caused the activation of caspase-3 beginning after 2-3 h, followed by eventual cell death. Oxotremorine-M pretreatment protected cells from H 2 O 2 -induced caspase-3 activation and death, and this was equivalent to protection afforded by a caspase inhibitor. Muscarinic receptor stimulation also protected cells from caspase-3 activation induced by exposure to rotenone, a mitochondrial complex 1 inhibitor, but no protection was evident from staurosporine-induced caspase-3 activation. The mechanism of protection afforded by muscarinic receptor activation from camptothecin-induced apoptotic signaling involved blockade of mitochondrial cytochrome c release associated with a bolstering of mitochondrial bcl-2 levels and blockade of the translocation of Bax to mitochondria. Likely the most proximal of these events to muscarinic receptor activation, mitochondrial Bax accumulation, also was attenuated by oxotremorine-M treatment after treatment with H 2 O 2 or rotenone. These results demonstrate that stimulation of muscarinic receptors provides substantial protection from DNA damage, oxidative stress, and mitochondrial impairment, insults that may be encountered by neurons in development, aging, or neurodegenerative diseases. These findings suggest that neurotransmitter-induced signaling bolsters survival mechanisms, and inadequate neurotransmission may exacerbate neuronal loss.

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Section: Stimulation Of Muscarinic Receptors Protects Against Rotenonsupporting

confidence: 93%

Muscarinic Receptor Activation Protects Cells from Apoptotic Effects of DNA Damage, Oxidative Stress, and Mitochondrial Inhibition

Sarno

Shestopal

King

et al. 2003

Journal of Biological Chemistry

107

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“…For example, overexpression GSK3␤ was shown to be sufficient to induce apoptosis (23), moderately overexpressed GSK3␤ facilitated apoptosis induced by staurosporine or heat shock (24) or mitochondrial complex 1 inhibitors (25), and inhibition of the phosphatidylinositol 3-ki- FIG. 3.…”

Section: Discussionmentioning

confidence: 99%

“…Further studies have extended the known links between GSK3␤ and apoptosis. Moderate overexpression of GSK3␤ (3.5-fold), which was insufficient to induce apoptosis alone, facilitated apoptosis induced by stressors (24,25). The human immunodeficiency virus type 1 regulatory protein, Tat, induced neuronal apoptosis in a GSK3␤-dependent manner, a signal mediated by platelet-activating factor receptor-induced activation of GSK3␤ (26,27).…”

mentioning

confidence: 99%

Central Role of Glycogen Synthase Kinase-3β in Endoplasmic Reticulum Stress-induced Caspase-3 Activation

Lee

Sarno

Jope

2002

Journal of Biological Chemistry

256

240

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Stress of the endoplasmic reticulum (ER), which is associated with many neurodegenerative conditions, can lead to the elimination of affected cells by apoptosis through only partially understood mechanisms. Thapsigargin, which causes ER stress by inhibiting the ER Ca 2؉ -ATPase, was found to not only activate the apoptosis effector caspase-3 but also to cause a large and prolonged increase in the activity of glycogen synthase kinase-3␤ (GSK3␤). Activation of GSK3␤ was obligatory for thapsigargin-induced activation of caspase-3, because inhibition of GSK3␤ by expression of dominantnegative GSK3␤ or by the GSK3␤ inhibitor lithium blocked caspase-3 activation. Thapsigargin treatment activated GSK3␤ by inducing dephosphorylation of phospho-Ser-9 of GSK3␤, a phosphorylation that normally maintains GSK3␤ inactivated. Caspase-3 activation induced by thapsigargin was blocked by increasing the phosphorylation of Ser-9-GSK3␤ with insulin-like growth factor-1 or with the phosphatase inhibitors okadaic acid and calyculin A, but the calcineurin inhibitors FK506 and cyclosporin A were ineffective. Insulin-like growth factor-1, okadaic acid, calyculin A, and lithium also protected cells from two other inducers of ER stress, tunicamycin and brefeldin A. Thus, ER stress activates GSK3␤ through dephosphorylation of phospho-Ser-9, a prerequisite for caspase-3 activation, and this process is amenable to pharmacological intervention.

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“…41 Furthermore, caspase-3 activation induced by inhibition of mitochondrial complex I has been shown to be facilitated by GSK-3b. 42 Since both PI3K-PKB/Akt as well as Wnt signaling inhibit GSK-3b activity, one might speculate that a DDC-4/sFRP-4-induced inhibition of the Wnt pathway reactivates GSK-3b and thereby promotes cell death. Recent reports by Song et al 43 and Fukumoto et al 44 indicate that the Wnt pathway can phosphorylate and activate PK-B/Akt via another intermediate player, dishevelled.…”

Section: Discussionmentioning

confidence: 99%

Role of DDC-4/sFRP-4, a secreted Frizzled-related protein, at the onset of apoptosis in mammary involution

et al. 2003

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Using differential display, we isolated DDC-4, a secreted frizzled-related protein (sFRP), which is induced in the physiological apoptosis of hormonally regulated, reproductive tissues such as mammary gland, prostate, corpus luteum and uterus. The role of this gene in apoptosis was studied in animals overexpressing ectopic DDC-4/sFRP-4. Transgenic mice bearing the DDC-4/sFRP-4 cDNA under the control of the MMTV-LTR promoter showed lactational insufficiency and many apoptotic cells in the alveoli between day 19 of pregnancy and day 4 of lactation as demonstrated by TUNEL reaction and the presence of activated caspase-3. We performed a PKB/Akt kinase assay and studied several of its substrates using phosphorylation-specific antibodies to show reduced phosphorylation in PKB/Akt itself, as well as in glycogen synthetase kinase-3b (GSK-3b), BAD, and Forkhead. Taken together, our results show a role for DDC-4/sFRP-4 in abrogating an epithelial cell survival pathway at the onset of mammary gland involution.

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Caspase-3 activation induced by inhibition of mitochondrial complex I is facilitated by glycogen synthase kinase-3β and attenuated by lithium

Cited by 174 publications

References 56 publications

Muscarinic Receptor Activation Protects Cells from Apoptotic Effects of DNA Damage, Oxidative Stress, and Mitochondrial Inhibition

Muscarinic Receptor Activation Protects Cells from Apoptotic Effects of DNA Damage, Oxidative Stress, and Mitochondrial Inhibition

Central Role of Glycogen Synthase Kinase-3β in Endoplasmic Reticulum Stress-induced Caspase-3 Activation

Role of DDC-4/sFRP-4, a secreted Frizzled-related protein, at the onset of apoptosis in mammary involution

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