Region of caspase-3 activation and programmed cell death in the early development of the mouse forebrain

2003 ◽  
Vol 145 (2) ◽  
pp. 241-248 ◽  
Author(s):  
Koko Urase ◽  
Yoriko Kouroku ◽  
Eriko Fujita ◽  
Takashi Momoi
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Early Development ◽  
Caspase 3

scholarly journals Cell Death and Metabolic Stress in Gymnodinium catenatum Induced by Allelopathy

Toxins ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 506
Author(s):  
Leyberth José Fernández-Herrera ◽  
Christine Johanna Band-Schmidt ◽  
Tania Zenteno-Savín ◽  
Ignacio Leyva-Valencia ◽  
Claudia Judith Hernández-Guerrero ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Protein Content ◽  
Caspase 3 ◽  
Cellular Stress ◽  
Allelopathic Effect ◽  
Sod Activity ◽  
Free Media ◽  
O2 Production ◽  
Gymnodinium Catenatum

Allelopathy between phytoplankton species can promote cellular stress and programmed cell death (PCD). The raphidophyte Chattonella marina var. marina, and the dinoflagellates Margalefidinium polykrikoides and Gymnodinium impudicum have allelopathic effects on Gymnodinium catenatum; however, the physiological mechanisms are unknown. We evaluated whether the allelopathic effect promotes cellular stress and activates PCD in G. catenatum. Cultures of G. catenatum were exposed to cell-free media of C. marina var. marina, M. polykrikoides and G. impudicum. The mortality, superoxide radical (O2●−) production, thiobarbituric acid reactive substances (TBARS) levels, superoxide dismutase (SOD) activity, protein content, and caspase-3 activity were quantified. Mortality (between 57 and 79%) was registered in G. catenatum after exposure to cell-free media of the three species. The maximal O2●− production occurred with C. marina var. marina cell-free media. The highest TBARS levels and SOD activity in G. catenatum were recorded with cell-free media from G. impudicum. The highest protein content was recorded with cell-free media from M. polykrikoides. All cell-free media caused an increase in the activity of caspase-3. These results indicate that the allelopathic effect in G. catenatum promotes cell stress and caspase-3 activation, as a signal for the induction of programmed cell death.

scholarly journals Caspase-3 deficiency reveals a physiologic role for Smac/DIABLO in regulating programmed cell death

2011 ◽  
Vol 18 (11) ◽  
pp. 1780-1790 ◽  
Author(s):  
K K W Hui ◽  
A K Kanungo ◽  
A J Elia ◽  
J T Henderson
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Caspase 3 ◽  
Physiologic Role

Proapoptotic Bid Preserves HSC Function through Restraint of Necroptosis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 251-251
Author(s):  
Patrice N. Wagner ◽  
Qiong Shi ◽  
Yuri D. Fedoriw ◽  
Sandra S. Zinkel
Keyword(s):  
Bone Marrow ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Mouse Model ◽  
Caspase 3 ◽  
Bone Marrow Failure ◽  
Marrow Cell ◽  
Caspase 8 ◽  
Complex Ii ◽  
A Cell

Abstract Multicellular organisms remove damaged or superfluous cells through a highly regulated cellular process known as programmed cell death. There are two main forms of programmed cell death, apoptosis and necrosis. Necrosis (necroptosis) previously thought to be an unregulated death pathway was recently found to be highly regulated. The manner by which a cell dies has important implications. In apoptotic cell death, caspases digest the cell to cause implosion in an immunologically silent process. In necroptotic cell death, increased Rip kinase signaling effects rupture of the plasma membrane, cellular explosion, and the activation of an inflammatory response. Death receptors, such as the TNFα receptor, can activate either apoptotic or necroptotic death. The upstream activators and transducers including Caspase-8, Rip1, and Fadd, are common to both forms of cell death. Interestingly, Caspase-8 and c-FlipL, a caspase homolog, were recently shown to inhibit the necrotic pathway during embryonic development through the formation of a catalytically active complex. The BH3-only Bcl-2 family member, Bid is one of the strongest substrates of Caspase-8, placing it at the interface of the apoptotic and necroptotic pathways, and in position to mediate cell death fate. The role of apoptosis in hematopoietic homeostasis has been well characterized. We developed a mouse model of unrestrained necroptosis in order to determine how unrestrained necroptosis impacts hematopoietic homeostasis and bone marrow function. To do this we generated a mouse model in which apoptosis is prevented by the deletion of the pro-apoptotic effectors Bax and Bak. We further deleted the upstream activator Bid (VavBaxBakBid TKO mice). Surprisingly, these mice die of bone marrow failure due to unrestrained necroptotic cell death. TKO bone marrow displays necroptotic cells by electron microscopy, and markedly increased Rip1 expression by immunofluorescence. TKO mice die of bone marrow failure with marked myeloid dysplasia between the age of 3 and 12 months, and a small number develop leukemia, a phenotype that closely resembles MDS. Further analysis revealed expansion and increased BrdU incorporation of the SLAM-HSC population, consistent with increased HSC proliferation in response to death of more mature cells. To assess function of these HSCs, we performed competitive reconstitution assays. TKO bone marrow initially outcompetes WT bone marrow, but the mice eventually succumb to bone marrow failure beginning at 5 months post–transplantation, despite the presence of ~10-15% wild type bone marrow. These results demonstrate that increased necroptotic signaling results in a cell autonomous stem cell defect. In addition, the presence of necroptotic bone marrow also kills normal HSCs in a non cell-autonomous manner, due to a feed-forward inflammatory process. To further characterize how necroptotic cell death is regulated, we developed myeloid progenitor cell lines (MPCs) from the bone marrow of WT, Bid KO, BaxBak DKO, and BaxBakBid TKO mice to facilitate biochemical and mechanistic studies. Our studies demonstrated increased activation (phosphorylation) and markedly increased levels of Rip1 in the pronecrotic complex (Complex II) with Rip3, Caspase-8, and Fadd in our TKO MPCs following LPS treatment. This association of Rip1 with Complex II is abrogated by reintroduction of Bid by retrovirus into TKO MPCs, demonstrating that Bid inhibits Rip1 association with complex II, suggesting that Bid is a key factor that determines cell death fate. Increased bone marrow cell death is well documented in MDS. To determine if necroptosis plays a role in this bone marrow cell death, we evaluated RIP1 and Caspase 3 expression in 17 human MDS samples. Remarkably, we found increased RIP1 expression, but not activated caspase 3 in bone marrow samples from patients with the RCMD, RAEB-1, and RAEB-2 subtype of MDS, but not in 4 control bone marrow samples (normal lymphoma staging marrows). Our study thus demonstrates that increased necroptosis signaling can result in bone marrow failure with dysplasia, and that necroptotic cell death signaling is increased in bone marrow from MDS patients, highlighting the potential importance of this targetable signaling pathway in bone marrow failure disorders such as MDS. Disclosures No relevant conflicts of interest to declare.

CASPASE-3 MEDIATED PROGRAMMED-CELL DEATH (APOPTOSIS) AFTER TRAUMATIC BRAIN INJURY IN RATS

1999 ◽  
Vol 27 (Supplement) ◽  
pp. 53A
Author(s):  
Robert S. B. Clark ◽  
Patrick M. Kochanek ◽  
Simon C. Watkins ◽  
Minzhi Chen ◽  
Neal A. Seidberg ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Cell Death ◽  
Brain Injury ◽  
Programmed Cell Death ◽  
Caspase 3
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