Caspase‐3 mediates retinoid‐induced apoptosis in the organogenesis‐stage mouse limb

Ali‐Khan, Sarah E.; Hales, Barbara F.

doi:10.1002/bdra.10090

Cited by 24 publications

(12 citation statements)

References 51 publications

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“…Indeed, while in the embryonic head an activation of downstream effector caspase 3 was found to be associated with the release of cytochrome c and an activation of initiator caspase 9, suggesting the involvement of the intrinsic proapoptotic pathway, no activation of this or another initiator caspase 8 was found in the limbs. The increase in cytoplasmic cytochrome c induced by high concentrations of vitamin A observed by Ali-Khan and Hales (2003), which does suggest mitochondrial involvement, does not appear to exclude the possibility that mechanisms activating caspase 3 in embryonic limbs differ from those acting in the embryonic head.…”

Section: Caspasesmentioning

confidence: 64%

“…At the same time, in mouse embryonic limbs cultured with 4-hydroperoxycyclophosphamide (4-OOHCPA), a teratogenic metabolite of CP, only the activation of caspase 3, but not caspases 9 and 8, has been observed (Huang and Hales, 2002). No activation of caspases 9 and 8, but only the activation of caspase 3, was also observed in mouse embryonic limbs cultured with another teratogen, vitamin A (Ali- Khan and Hales, 2003). Importantly, the above studies suggest that apoptotic mechanisms acting upstream of the effector caspase 3 may differ in different embryonic structures.…”

Section: Caspasesmentioning

confidence: 82%

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Teratogen-induced apoptotic cell death: Does the apoptotic machinery act as a protector of embryos exposed to teratogens?

2005

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Considerable evidence has been collected demonstrating that many teratogens induce apoptotic cell death in embryonic structures that turn out to be malformed in fetuses and newborns. Apoptosis is a genetically regulated process that is realized by the activation of death and pro-survival signaling cascades, and the interplay between these cascades determines whether the cell exposed to apoptotic stimuli dies or survives. Therefore, there is intense interest in understanding how the apoptotic machinery functions in embryos exposed to teratogens. However, the interpretation of the results obtained remains problematic. The main problem is that excessive embryonic cell death, regardless of its nature, if uncompensated for, ultimately leads to maldevelopment or embryonic death. Therefore, we can easily interpret results when the intensity of teratogen-induced cell death and the severity or incidence of teratogen-induced anomalies directly correlate with each other. However, when teratogen-induced cell death is not followed by the formation of anomalies, a usual explanation is that teratogen-induced apoptotic cell death contributes to the renewal of teratogen-targeted cell populations by promoting the removal of injured cells. It is clear that such an explanation leaves vague the role of the anti-apoptotic signaling mechanism (and, hence, the apoptotic machinery as a whole) with respect to protecting the embryo against teratogenic stress. In this review, we summarize the data from studies addressing the function of the apoptotic machinery in embryos exposed to teratogens, and then we discuss approaches to interpreting the results of these studies. We hypothesize that activation of a proapoptotic signaling in teratogen-targeted cell populations is a necessary condition for an anti-apoptotic signaling that counteracts the process of maldevelopment to be activated. If such a scenario is true, we need to modify our approaches to choosing molecular targets for studies addressing this topic.

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Section: Caspasesmentioning

confidence: 64%

Section: Caspasesmentioning

confidence: 82%

Teratogen-induced apoptotic cell death: Does the apoptotic machinery act as a protector of embryos exposed to teratogens?

2005

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“…It should be noted that exposure to monoener- getic neutrons hastened cell death programmed during the process of organ maturation. Radiation exposure in utero induced apoptosis in the predigital regions of embryonic limb buds, where cells were programmed to die within the following 2 days [1]. Susceptibility to radiation in the predigital regions and defects of the digits depended on both the Trp53 status and the radiation dose [29,30].…”

Section: Discussionmentioning

confidence: 99%

Effect of Monoenergetic Neutron Irradiation on the Postnatal Development of the Cochlea in C3H/HeN Mice

Nitta

Araki

Nitta³

et al. 2005

The Journal of Veterinary Medical Science

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ABSTRACT. To investigate the toxic effect of neutrons at energies of approximately 1MeV on the ear, we exposed 7-day-old mice to 1.0 Gy of monoenergetic neutrons (1.026 MeV) or 137 Cs gamma rays, and assessed subsequent morphological changes in the inner ear by light and scanning electron microscopy. Monoenergetic neutrons, but not gamma rays, caused acute changes in the ear. The epithelium of the greater epithelial ridge in the organ of Corti had disappeared by 72 hr post-irradiation, as a result of epithelial apoptosis observed 6 hr post-irradiation. Radiation could induce apoptotic cell death of the epithelium of the greater epithelial ridge at 3 or 4 days of age. Protruding structures were detected on the surface of the hair cells by 72 hr post-irradiation. The neutron-irradiation also caused the apoptotic cell death of epithelial cells at the nasal conchae, and subsequent acute otitis media continued until 10 weeks of age. KEY WORDS: cochlear degeneration, high linear energy transfer radiation, mouse, neutron, scanning electron microscopy.

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“…2003). Other studies have shown that retinoic acid (Ali‐Khan & Hales 2003) and cadmium (Fernandez et al . 2003) also induce activation of procaspe‐3.…”

Section: Biochemistry Of Teratogen‐induced Cell Deathmentioning

confidence: 95%

Cell death in normal and abnormal development

Mirkes

2008

Congenital Anomalies

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Research over the past 50 years has consistently documented that cell death is an integral part of both normal development and the etiology of birth defects; however, the significance of this cell death has been, until recently, unclear. Research published during the past 15 years has now shown that programmed cell death (PCD) and teratogen-induced cell death are genetically controlled processes (apoptosis) that play important roles in both normal and abnormal development. Therefore, the purpose of this review is to highlight what is known about PCD and teratogen-induced cell death and their relationships to the mechanisms of apoptosis and abnormal development.

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Caspase‐3 mediates retinoid‐induced apoptosis in the organogenesis‐stage mouse limb

Abstract: Caspase-3 is a key effector caspase in the apoptotic pathway induced by Vitamin A. While caspases-8 and -9 are not responsible for the activation of caspase-3 in response to the drug, cytochrome-c release from mitochondria may play an upstream role.

Cited by 24 publications

References 51 publications

Teratogen-induced apoptotic cell death: Does the apoptotic machinery act as a protector of embryos exposed to teratogens?

Teratogen-induced apoptotic cell death: Does the apoptotic machinery act as a protector of embryos exposed to teratogens?

Effect of Monoenergetic Neutron Irradiation on the Postnatal Development of the Cochlea in C3H/HeN Mice

Cell death in normal and abnormal development

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