Temporal profile of nuclear DNA fragmentation in situ in gerbil hippocampus following transient forebrain ischemia

Iwai, Tomohiko; Hara, Akira; Niwa, Masayuki; Nozaki, Masakatsu; Uematsu, Toshihiko; Sakai, Noboru; Yamada, Hideaki

doi:10.1016/0006-8993(94)01363-m

Cited by 69 publications

(26 citation statements)

References 14 publications

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“…Besides characteristic morphology, the state of integrity of chromatin remains the sole ac ceptable hallmark of apoptosis (Wyllie et al, 1980;Buja et al, 1993;Bortner et al, 1995;Walker et al, 1995). Since the first reports in 1993 of DNA fragmen tation following cerebral ischemia (Heron et al, 1993;Linnik et al, 1993;MacManus et al, 1993;Okamoto et al, 1993;Tominaga et al, 1993), there have been many others on transient global ischemia Sei et al, 1994;Iwai et al, 1995;Nitatori et al, 1995;Charriaut-Marlangue et al, 1996a,b), focal ischemia (MacManus et al, 1994;Li et al, 1995a-c;Linnik et al, 1995;Du et al, 1996), and neonatal hypoxia ischemia Hill et al, 1995) models. The oft-repeated observation of DNA dam age visualized as electrophoretic laddered DNA frag ments of oligonucleosomal size in ischemic rodent brain has led to the suggestion that ischemic cell death may be apoptotic.…”

Section: Discussionmentioning

confidence: 99%

“…However, an impressive num ber of reports since 1993 have demonstrated the pres ence of apoptotic-like laddered DNA following an ischemic insult. These have been in both global (Fer rer et al, 1994;Heron et al, 1993;Iwai et al, 1995;Nitatori et al, 1995;Okamoto et al, 1993;Tortosa et al, 1994) and focal (Li et al, 1995a-c; Linnik et al, 1993 andTominaga et al, 1993;Sei et al, 1994) models of transient brain hemostasis. Some of this evidence came from this laboratory, where we concluded that a component of the apoptotic degra dative machinery is at work in the ischemic neurons (Hill et al, 1995;MacManus 1993MacManus , 1994MacManus , 1995a.…”

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confidence: 99%

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Detection of Higher-Order 50- and 10-kbp DNA Fragments before Apoptotic Internucleosomal Cleavage after Transient Cerebral Ischemia

MacManus

Rasquinha

Tuor

et al. 1997

J Cereb Blood Flow Metab

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Summary: DNA fragments of SO and 10 kbp were found in ischemic brain in adult rats following two-vessel occlu sion or in neonates following hypoxia-ischemia. These higher-order fragments were detected before any laddered oligonucleosomal DNA fragmentation characteristic of apoptosis. Both the SO-and 10-kbp fragments were also detected during necrosis produced by decapitation, but these led to smeared smaller fragments, not laddered pat terns. End-group analysis showed the presence of both 3' OH and S;-OH ends in both the SO-and lO-kbp fragments

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Detection of Higher-Order 50- and 10-kbp DNA Fragments before Apoptotic Internucleosomal Cleavage after Transient Cerebral Ischemia

MacManus

Rasquinha

Tuor

et al. 1997

J Cereb Blood Flow Metab

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“…However, the present results indicate that there is an absolute threshold for CA1 neuron loss of 3 to 4 mins depolarization, below which no appreciable damage will be evident even at prolonged recirculation intervals. Somewhat lower thresholds may be expected for medial CA1/subiculum (Iwai et al, 1995), while injury grades that incorporate less vulnerable lateral CA1 contribute to a flattening of the threshold relationship (Xu et al, 1999). (Left panels) Naive rats and animals subjected to optimal preconditioning at a 2-day interval (PC) were subjected to test depolarization of the indicated durations, and inflammation in the CA1 region was graded at 1, 2, and 4 weeks.…”

Section: Temporal Factors In Ischemic Injury and Preconditioningmentioning

confidence: 99%

Protective Preconditioning by Transient Global Ischemia in the Rat: Components of Delayed Injury Progression and Lasting Protection Distinguished by Comparisons of Depolarization Thresholds for Cell Loss at Long Survival Times

Ueda

Nowak²

2005

J Cereb Blood Flow Metab

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Robust ischemic preconditioning has been shown in rodent brain, but there are concerns regarding the persistence of neuron protection. This issue was examined in rat hippocampus following 4-vessel occlusion (4-VO) ischemia, using DC shifts characteristic of ischemic depolarization to reproducibly define insult severity. Preconditioning ischemia producing 2 to 3.5 mins depolarization was followed at intervals of 2, 5, or 7 days by test insults of varied duration, after which CA1 counts were obtained at 1, 2, 4, or 12 weeks. Neuron loss in naive animals increased with depolarization time longer than 4 mins regardless of postischemic survival interval. Preconditioning 2, 5, or 7 days before test insults prolonged the injury threshold evaluated at 1 week survival to 15, 9, or 6 mins, respectively, showing robust protection and a rapid decay of the protected state. However, by 2 weeks survival after preconditioning at a 2-day interval, the injury threshold dramatically regressed from 15 to 9 mins. Thereafter protection remained relatively stable through 1 month, but slight progression of neuron injury was evident at 3 months. Inflammatory responses were seen in both naive and preconditioned hippocampi throughout this interval, appropriate to the extent of neuron injury. These studies show distinct components of transient and lasting protection after ischemic preconditioning. Finally, it was found that ischemic depolarization was delayed by approximately 1 min in optimally preconditioned rat hippocampus, in contrast to previous results in the gerbil, identifying one specific mechanism by which insult severity is reduced in this model.

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“…Impaired survival activity of primary neurons derived from AMSH-deficient mice. Hippocampal CA1 neurons are known to be susceptible to hypoglycemia, anoxia, and metabolic stresses, which lead to the induction of apoptotic cell death (7,8,10,11,14,24). To exclude the possibility that the loss of AMSH-deficient hippocampal neurons was mediated by such stresses, we prepared in vitro primary cultures of hippocampal neurons isolated from AMSH ϩ/ϩ and AMSH Ϫ/Ϫ embryos at E18.5.…”

Section: Generation Of Amsh-deficient Micementioning

confidence: 99%

Loss of Neurons in the Hippocampus and Cerebral Cortex of AMSH-Deficient Mice

Ishii¹,

Owada

Yamada³

et al. 2001

Molecular and Cellular Biology

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AMSH, a molecule that associates with STAM1, is involved in the in vitro cell growth signaling mediated by interleukin 2 and granulocyte-macrophage colony-stimulating factor. To investigate the in vivo functional role of AMSH, we have generated AMSH-deficient mice by gene targeting. The AMSH-deficient mice were morphologically indistinguishable from their littermates at birth, and histopathological examinations revealed normal morphogenesis in all tissues tested. However, all the AMSH-deficient mice exhibited postnatal growth retardation and died between postnatal day 19 (P19) and P23. Examination of brain sections at P6 demonstrated significant loss of neurons and apoptotic cells in the CA1 subfield of the hippocampus. Brain atrophy developed by P16 and was accompanied by complete loss of the CA1 neurons in the hippocampus and marked atrophy of the cerebral cortex. Furthermore, AMSH-deficient hippocampal neuronal cells were unable to survive in vitro, even in the presence of several stimulatory cytokines, while AMSH-deficient cerebellar neurons, thymocytes, and embryonic fibroblasts survived normally. Taken together, these observations indicate that AMSH is an essential molecule for the survival of neuronal cells in early postnatal mice.Cytokines are essential factors for cell activation, differentiation, survival, and apoptosis in many biological events. The effects of cytokines on target cells are mediated by their interactions with specific receptors, which transduce the intracellular signals in the target cells. Among the many cytokines, interleukin 2 (IL-2) is known to be a critical soluble ligand for activating T cells in immune responses (12,34,35). During the search for signaling molecules involved in the IL-2-mediated signaling pathway, we identified the STAM family of molecules, STAM1 and STAM2, both of which are associated with Jak2 and Jak3 tyrosine kinases (9,36,37). We subsequently isolated a novel adapter molecule from human T cells that we named AMSH, for associated molecule with the SH3 domain of STAM1 (39). Recently, a novel SH3-binding motif (SBM) of AMSH that interacts with the SH3 domain of both STAM1 and STAM2 was identified (17, 39). SH3 deletion mutants of the STAMs act as dominant-negative forms in signaling that induces cell growth, and the wild-type, but not the mutant, STAMs enhance c-myc induction that is mediated by IL-2 and granulocyte-macrophage colony-stimulating factor (GM-CSF) (37). Hence, we hypothesized that AMSH might be involved in the cytokine-mediated signaling through its interaction with the STAMs. In this context, we have already demonstrated that an AMSH mutant with its C-terminal half deleted and retaining its STAM1-binding ability confers a dominant-negative effect on IL-2-and GM-CSF-mediated signaling pathways that induce DNA synthesis and c-myc transcription (39). The deleted C terminus of AMSH contained an Mov34/MPN domain (3), which is conserved in several subunits of the COP9 signalsome, although the function of this domain is still unknown. Collectively, thes...

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Temporal profile of nuclear DNA fragmentation in situ in gerbil hippocampus following transient forebrain ischemia

Cited by 69 publications

References 14 publications

Detection of Higher-Order 50- and 10-kbp DNA Fragments before Apoptotic Internucleosomal Cleavage after Transient Cerebral Ischemia

Detection of Higher-Order 50- and 10-kbp DNA Fragments before Apoptotic Internucleosomal Cleavage after Transient Cerebral Ischemia

Protective Preconditioning by Transient Global Ischemia in the Rat: Components of Delayed Injury Progression and Lasting Protection Distinguished by Comparisons of Depolarization Thresholds for Cell Loss at Long Survival Times

Loss of Neurons in the Hippocampus and Cerebral Cortex of AMSH-Deficient Mice

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