An age‐related increase in resistance to DNA damage‐induced apoptotic cell death is associated with development of DNA repair mechanisms

Romero, Alejandro A.; Gross, Stephane R.; Cheng, Ke-Yi; Goldsmith, Noriko K.; Geller, Herbert M.

doi:10.1046/j.1471-4159.2003.01629.x

Cited by 22 publications

(21 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is clear that the vulnerability of the brain is strongly influenced by age, although the mechanisms behind these developmental changes are only partly understood. 2,9,22,44 The influence of age on cell death mechanisms Activation of caspase-3 appears to be a critical event in the execution of neuronal apoptosis in the brain during development and after acute injury. 1,21,[23][24][25] In this study, we examined caspase-3 during normal development and after HI.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The influence of age on apoptotic and other mechanisms of cell death after cerebral hypoxia–ischemia

et al. 2004

View full text Add to dashboard Cite

Unilateral hypoxia-ischemia (HI) was induced in C57/BL6 male mice on postnatal day (P) 5, 9, 21 and 60, corresponding developmentally to premature, term, juvenile and adult human brains, respectively. HI duration was adjusted to obtain a similar extent of brain injury at all ages. Apoptotic mechanisms (nuclear translocation of apoptosis-inducing factor, cytochrome c release and caspase-3 activation) were several-fold more pronounced in immature than in juvenile and adult brains. Necrosis-related calpain activation was similar at all ages. The CA1 subfield shifted from apoptosis-related neuronal death at P5 and P9 to necrosis-related calpain activation at P21 and P60. Oxidative stress (nitrotyrosine formation) was also similar at all ages. Autophagy, as judged by the autophagosome-related marker LC-3 II, was more pronounced in adult brains. To our knowledge, this is the first report demonstrating developmental regulation of AIF-mediated cell death as well as involvement of autophagy in a model of brain injury.

show abstract

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4][5][6][7] It is generally accepted that neurons in the immature brain tolerate a longer period of oxygen deprivation and/or ischemia than those in the adult brain. 1,3 However, there are conflicting reports, showing that the immature brain is less resistant to HI brain damage than its adult counterpart.…”

Section: Introductionmentioning

confidence: 99%

The influence of age on apoptotic and other mechanisms of cell death after cerebral hypoxia–ischemia

et al. 2004

View full text Add to dashboard Cite

show abstract

“…Details of NER (Lagerwerf et al, 2011) and BER (Robertson et al, 2009) pathways have been recently reviewed. The gradual maturation of such repair mechanisms in neurons is shown by the fact that mature neurons appear to be more resistant to UV- and IR-induced DNA damage than their younger counterparts (Romero et al, 2003; Shirai et al, 2006). Neurons are also more resistant to IR-induced apoptosis compared to neuronal precursor cells (Kameyama and Inouye, 1994) and other cell types (Li et al, 1996).…”

Section: Neuronal Responsesmentioning

confidence: 99%

“…Neurons are also more resistant to IR-induced apoptosis compared to neuronal precursor cells (Kameyama and Inouye, 1994) and other cell types (Li et al, 1996). This highlights the importance of efficient DNA damage response (DDR) mechanisms to maintain mature post-mitotic cells, like neurons, which cannot be replenished (Romero et al, 2003). IR irradiation also affects multiple behavioral outputs of different species by affecting neurons (Sakashita et al, 2010 and references herein).…”

Section: Neuronal Responsesmentioning

confidence: 99%

Neuronal Responses to Physiological Stress

Kagias¹,

Nehammer²,

Pocock³

2012

Front. Gene.

View full text Add to dashboard Cite

Physiological stress can be defined as any external or internal condition that challenges the homeostasis of a cell or an organism. It can be divided into three different aspects: environmental stress, intrinsic developmental stress, and aging. Throughout life all living organisms are challenged by changes in the environment. Fluctuations in oxygen levels, temperature, and redox state for example, trigger molecular events that enable an organism to adapt, survive, and reproduce. In addition to external stressors, organisms experience stress associated with morphogenesis and changes in inner chemistry during normal development. For example, conditions such as intrinsic hypoxia and oxidative stress, due to an increase in tissue mass, have to be confronted by developing embryos in order to complete their development. Finally, organisms face the challenge of stochastic accumulation of molecular damage during aging that results in decline and eventual death. Studies have shown that the nervous system plays a pivotal role in responding to stress. Neurons not only receive and process information from the environment but also actively respond to various stresses to promote survival. These responses include changes in the expression of molecules such as transcription factors and microRNAs that regulate stress resistance and adaptation. Moreover, both intrinsic and extrinsic stresses have a tremendous impact on neuronal development and maintenance with implications in many diseases. Here, we review the responses of neurons to various physiological stressors at the molecular and cellular level.

show abstract

“…The extent of ischemic-hypoxic injury depends on the degree of maturation of the brain as well as [24][25][26][27][28][29][30] . Neurons in the immature brain can tolerate a longer period of oxygen deprivation and/or ischemia than the neurons in the adult brain [25,27] .…”

Section: Autophagy Is Activated In Ischemic And/or Hypoxic Damaged Brmentioning

confidence: 99%

Death and survival of neuronal and astrocytic cells in ischemic brain injury: a role of autophagy

Zhang

2011

Acta Pharmacol Sin

View full text Add to dashboard Cite

Autophagy is a highly regulated cellular mechanism that leads to degradation of long-lived proteins and dysfunctional organelles. The process has been implicated in a variety of physiological and pathological conditions relevant to neurological diseases. Recent studies show the existence of autophagy in cerebral ischemia, but no consensus has yet been reached regarding the functions of autophagy in this condition. This article highlights the activation of autophagy during cerebral ischemia and/or reperfusion, especially in neurons and astrocytes, as well as the role of autophagy in neuronal or astrocytic cell death and survival. We propose that physiological levels of autophagy, presumably caused by mild to modest hypoxia or ischemia, appear to be protective. However, high levels of autophagy caused by severe hypoxia or ischemia and/or reperfusion may cause self-digestion and eventual neuronal and astrocytic cell death. We also discuss that oxidative and endoplasmic reticulum (ER) stresses in cerebral hypoxia or ischemia and/or reperfusion are potent stimuli of autophagy in neurons and astrocytes. In addition, we review the evidence suggesting a considerable overlap between autophagy on one hand, and apoptosis, necrosis and necroptosis on the other hand, in determining the outcomes and final morphology of damaged neurons and astrocytes.

show abstract

An age‐related increase in resistance to DNA damage‐induced apoptotic cell death is associated with development of DNA repair mechanisms

Cited by 22 publications

References 60 publications

The influence of age on apoptotic and other mechanisms of cell death after cerebral hypoxia–ischemia

The influence of age on apoptotic and other mechanisms of cell death after cerebral hypoxia–ischemia

Neuronal Responses to Physiological Stress

Death and survival of neuronal and astrocytic cells in ischemic brain injury: a role of autophagy

Contact Info

Product

Resources

About