In situ immunodetection of activated caspase-3 in apoptotic neurons in the developing nervous system

Srinivasan, Anu; Roth, Kevin A.; Sayers, Robert O.; Shindler, Kenneth S.; Wong, Angela; Fritz, Lawrence C.; Tomaselli, Kevin J.

doi:10.1038/sj.cdd.4400449

Cited by 359 publications

(291 citation statements)

References 33 publications

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“…To confirm the existence of apoptosis, we used the cleaved caspase-3-specific antibody to stain the thoracic muscles for the activated Drice, [29][30][31] the Drosophila homolog of mammalian caspase-3, which resides in the cytosol as an inactive zymogen (procaspase-3) and translocates to the nucleus after proteolytic activation. 32 The cleaved caspase-3 staining was observed either associated or within 480% of the muscle nuclei of aged dYME1L del flies, but could hardly be detected in either young dYME1L del flies or wild-type flies (Figures 4a and b i-AAA mutation causes apoptotic degeneration Y Qi et al and Supplementary Figure S3a).…”

Section: Resultsmentioning

confidence: 99%

Loss of Drosophila i-AAA protease, dYME1L, causes abnormal mitochondria and apoptotic degeneration

Liu

Daniels

et al. 2015

Cell Death Differ

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Mitochondrial AAA (ATPases Associated with diverse cellular Activities) proteases i-AAA (intermembrane space-AAA) and m-AAA (matrix-AAA) are closely related and have major roles in inner membrane protein homeostasis. Mutations of m-AAA proteases are associated with neuromuscular disorders in humans. However, the role of i-AAA in metazoans is poorly understood. We generated a deletion affecting Drosophila i-AAA, dYME1L (dYME1L del ). Mutant flies exhibited premature aging, progressive locomotor deficiency and neurodegeneration that resemble some key features of m-AAA diseases. dYME1L del flies displayed elevated mitochondrial unfolded protein stress and irregular cristae. Aged dYME1L del flies had reduced complex I (NADH/ubiquinone oxidoreductase) activity, increased level of reactive oxygen species (ROS), severely disorganized mitochondrial membranes and increased apoptosis. Furthermore, inhibiting apoptosis by targeting dOmi (Drosophila Htra2/Omi) or DIAP1, or reducing ROS accumulation suppressed retinal degeneration. Our results suggest that i-AAA is essential for removing unfolded proteins and maintaining mitochondrial membrane architecture. Loss of i-AAA leads to the accumulation of oxidative damage and progressive deterioration of membrane integrity, which might contribute to apoptosis upon the release of proapoptotic molecules such as dOmi. Containing ROS level could be a potential strategy to manage mitochondrial AAA protease deficiency.

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Section: Resultsmentioning

confidence: 99%

Loss of Drosophila i-AAA protease, dYME1L, causes abnormal mitochondria and apoptotic degeneration

Liu

Daniels

et al. 2015

Cell Death Differ

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“…TRAIL-mediated cell apoptosis proceeds by binding to two TRAIL receptors, DR4 and DR5, with subsequent activation of caspases via the receptor's intracellular death domains [16]. The characteristic changes of cell apoptosis are nuclear fragmentation, detected by TUNEL [17], and active forms of caspases [18]. Fas Ligand represents another extracellular cell death signal which mediates apoptosis through its receptor, Fas [19].…”

Section: Introductionmentioning

confidence: 99%

Apoptosis in the skeletal muscle of untreated children with juvenile dermatomyositis: Impact of duration of untreated disease

Zhao

Fedczyna

McVicker

et al. 2007

Clinical Immunology

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Juvenile Dermatomyositis (JDM) is the most common myopathy in children with characteristic skin rash and muscle weakness, in which longer duration of untreated disease was associated with less muscle weakness. The duration of untreated inflammation may alter the apoptotic pathways involved in skeletal muscle damage. Diagnostic muscle biopsies from 14 untreated patients were stained for apoptosis markers. TUNEL-positive nuclei and caspase 3 were detected within the laminin layer, indicating apoptosis of skeletal muscle nuclei. Untreated JDM disease duration greater than 2 months ("long"), was associated with higher Fas positive cell counts in the perivascular region compared with the "short" disease duration group, 2 months or less. Within the "long" duration group, higher Fas positive cell counts were positively associated with increased TUNEL-positive nuclei and caspase 3. We conclude that the duration of untreated disease (chronic inflammation) influences the mode of continuing cell damage and death in children with JDM.

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“…Immunocytochemical staining for the cleaved p17 fragment of caspase-3 is a useful marker for apoptosis, both in vivo and in vitro, following a number of death-inducing insults. 27 To determine whether STS induced apoptosis in FGF2-expanded NPCs, we treated FGF2-expanded NPCs with STS for 6 h, fixed them with 4% paraformaldehyde, and assessed the appearance of cleaved 'activated' caspase-3 immunoreactivity and apoptotic nuclear features. For untreated NPCs, media were replaced at the onset of treatment and cells were fixed 6 h later.…”

Section: Introductionmentioning

confidence: 99%

Neural precursor cells possess multiple p53-dependent apoptotic pathways

et al. 2006

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Neural precursor cells (NPCs) are markedly sensitive to apoptotic insults. p53-dependent transcriptional activation of proapoptotic genes has been hypothesized to regulate NPC death in response to DNA damage. Recent studies of nonNPCs have also indicated that p53 may directly interact with Bcl-2 molecules and thereby regulate death independently of transcription. The contribution of transcription-independent p53 activation in NPC death has not been characterized. In this study, we found that apoptosis caused by chemotherapeutic agents in NPCs required p53 expression and new macromolecular synthesis. In contrast, NPC death induced by staurosporine, a broad kinase inhibitor, is regulated by p53 in the absence of macromolecular synthesis. The apoptosis effector molecules Bax and Bak, Apaf-1, and caspase-9 were shown to be downstream of p53 in both pathways. These findings indicate that p53 is in a unique position to regulate at least two distinct signaling portals that activate the intrinsic apoptotic death pathway in NPCs.

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In situ immunodetection of activated caspase-3 in apoptotic neurons in the developing nervous system

Cited by 359 publications

References 33 publications

Loss of Drosophila i-AAA protease, dYME1L, causes abnormal mitochondria and apoptotic degeneration

Loss of Drosophila i-AAA protease, dYME1L, causes abnormal mitochondria and apoptotic degeneration

Apoptosis in the skeletal muscle of untreated children with juvenile dermatomyositis: Impact of duration of untreated disease

Neural precursor cells possess multiple p53-dependent apoptotic pathways

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