Temporal profile of cytochrome c and caspase-3 immunoreactivities and TUNEL staining after permanent middle cerebral artery occlusion in rats

Sasaki, Chihoko; Kitagawa, Hisashi; Zhang, Wen Ri; Warita, Hitoshi; Sakai, Kenichi; Abe, Kōji

doi:10.1080/01616412.2000.11741065

Cited by 51 publications

(31 citation statements)

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“…These data suggest that SDF-1␣ could protect neurons from HIV-1 neurotoxicity via inhibition of caspase-3 activation. However, in cerebral ischemic models proapoptotic mechanisms are activated during ischemic-reperfusion to facilitate caspase-3-mediated cell death (Sasaki et al, 2000). In this study, we found that SDF-1␣ disrupts the downstream caspase-3 apoptotic signal in the ischemic penumbra of cerebral ischemic rats, resulting in cortical neuronal protection and a diminished infarct volume.…”

mentioning

confidence: 57%

Stromal Cell-Derived Factor-1α Promotes Neuroprotection, Angiogenesis, and Mobilization/Homing of Bone Marrow-Derived Cells in Stroke Rats

Shyu¹,

Lin²,

Yen³

et al. 2007

J Pharmacol Exp Ther

140

122

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Stromal cell-derived factor (SDF)-1␣ is involved in the trafficking of hematopoietic stem cells from bone marrow to peripheral blood, and its expression is increased in the penumbra of the ischemic brain. In this study, SDF-1␣ was found to exert neuroprotective effects that rescued primary cortical cultures from H 2 O 2 neurotoxicity, and to modulate neurotrophic factor expression. Rats receiving intracerebral administration of SDF-1␣ showed less cerebral infarction due to up-regulation of antiapoptotic proteins, and they had improved motor performance. SDF-1␣ injection enhanced the targeting of bone marrow (BM)-derived cells to the injured brain, as demonstrated in green fluorescent protein-chimeric mice with cerebral ischemia. In addition, increased vascular density in the ischemic cortex of SDF-1␣-treated rats enhanced functional local cerebral blood flow. In summary, intracerebral administration of SDF-1␣ resulted in neuroprotection against neurotoxic insult, and it induced increased BM-derived cell targeting to the ischemic brain, thereby reducing the volume of cerebral infarction and improving neural plasticity.Stroke is a major cause of mortality worldwide (van Gijn and Dennis, 1998), and bone marrow stem cell transplantation has been demonstrated to be a potential strategy for its treatment (Li et al., 2002). Under ischemic conditions, circulating stem cells seem to selectively migrate to ischemic regions to support the plasticity and functional recovery of damaged tissue (Orlic et al., 2001). However, the signals that guide stem cells to ischemic lesions are as yet unknown. Stromal cell-derived factor (SDF)-1␣, a CXC chemokine produced by bone marrow stromal cells, is a potent chemoattractant for hematopoietic stem cells (HSCs), and it is constitutively expressed by all tissues (Shirozu et al., 1995). Recent reports have indicated that SDF-1␣ is a strong chemoattractant for CD34 ϩ cells, which express CXCR4, the receptor for SDF-1␣, and play an important role in HSC trafficking between peripheral circulation and bone marrow (Petit et al., 2002). Studies of mice lacking SDF-1␣ or CXCR4 have confirmed that SDF-1␣ is necessary for the migration of HSCs from fetal liver to bone marrow (Zou et al., 1998). In addition, the expression of SDF-1␣ in the brains of human immunodeficiency virus (HIV)-positive patients suggests that SDF-1␣ may play a role in neuroprotection in response to HIV infection (Langford et al., 2002). Therefore, SDF-1␣/CXCR4 signaling may also play an important neuroprotective/neuroplastic role in the repair of neural tissue injury.Expression of CXCR4 and SDF-1␣ after focal cerebral ischemia (Stumm et al., 2002) led us to speculate that this chemokine may also signal adhesion and migration of HSCs to ischemic tissue. On this basis, we hypothesized that locally This work was supported in part by Chen-Han Foundation for Education, Academia Sinica Grant 94M003 and National Science Council Grant NSC95-2745-B-001-001-MY3.Article, publication date, and citation information can be found at...

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mentioning

confidence: 57%

Stromal Cell-Derived Factor-1α Promotes Neuroprotection, Angiogenesis, and Mobilization/Homing of Bone Marrow-Derived Cells in Stroke Rats

Shyu¹,

Lin²,

Yen³

et al. 2007

J Pharmacol Exp Ther

140

122

View full text Add to dashboard Cite

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“…The release of cytochrome c and other mitochondrial proteins from the intermembrane space to the cytosol is commonly a critical step in the death of cells by apoptosis that can result from disruption of the outer mitochondrial membrane due to swelling associated with induction of the permeability transition pore. However, alternative mechanisms that are independent of the permeability transition pore and of mitochondrial swelling are apparently often involved (Sasaki et al, 2000). Bax and some other member of the bcl-family of proteins have been implicated in this release process.…”

Section: Cytochrome C Release and Reperfusionmentioning

confidence: 99%

Cerebral Ischemia and Reperfusion: The Pathophysiologic Concept as a Basis for Clinical Therapy

Schaller

Graf

2004

J Cereb Blood Flow Metab

300

208

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The ischemic penumbra has been documented in the laboratory animal as severely hypoperfused, nonfunctional, but still viable brain tissue surrounding the irreversibly damaged ischemic core. Saving the penumbra is the main target of acute stroke therapy, and is the theoretical basis behind the reperfusion concept. In experimental focal ischemia, early reperfusion has been reported to both prevent infarct growth and aggravate edema formation and hemorrhage, depending on the severity and duration of prior ischemia and the efficiency of reperfusion, whereas neuronal damage with or without enlarged infarction also may result from reperfusion (so-called reperfusion injury). Activated neutrophils contribute to vascular reperfusion damage, yet posthypoxic cellular injury occurs in the absence of inflammatory species. Protein synthesis inhibition occurs in neurons during reperfusion after ischemia, underlying the role that these pathways play in prosurvival and proapoptotic processes that may be differentially expressed in vulnerable and resistant regions of the reperfused brain tissue. Ischemia-induced decreases in the mitochondrial capacity for respiratory activity probably contribute to the ongoing impairment of energy metabolism during reperfusion and possibly also the magnitude of changes seen during ischemia. From these experimental data, the concept of single-drug intervention cannot be effective. Further experimental research is needed, especially of the study of biochemical markers of the injury process to establish the role of several drugs.

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“…The time required for caspase activation induced in the brain either by ischemia (Han et al 2000;Sasaki et al 2000;Velier et al 1999) or chemical stimuli (Kondratyev and Gale 2000;Asakura et al 1999;Hayami et al 1999) ranges from several hours to one day after exposure to an apoptotic stimulus. In our study, we found that activation of caspase-3 took place either shortly after noise exposure or possibly during noise exposure.…”

Section: Discussionmentioning

confidence: 99%

The Caspase Pathway in Noise-Induced Apoptosis of the Chinchilla Cochlea

Nicotera

Henderson

2003

JARO - Journal of the Association for Research in Otolaryngolog

168

155

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We previously reported that intense noise exposure causes outer hair cell (OHC) death primarily through apoptosis. Here we investigated the intracellular signal pathways associated with apoptotic OHC death. Chinchillas were exposed to a 4 kHz narrowband noise at 110 dB SPL for 1 h. After the noise exposure, the cochleas were examined for the activity of each of three caspases, including caspase-3, -8, or -9 with carboxyfluorescein-labeled fluoromethyl ketone (FMK)-peptide inhibitors. The cochleas were further examined for cytochrome c release from mitochondria by immunohistology and for DNA degradation by the TUNEL method. The results showed that the noise exposure triggered activation of caspase-3, an important mediator of apoptosis. The noise exposure also caused the activation of caspase-8 and caspase-9, each of which is associated with a distinct signaling pathway that leads to activation of caspase-3. Caspase activation occurred only in the apoptotic OHCs and not in the necrotic OHCs. These results indicate that multiple signaling pathways leading to caspase-3 activation take place simultaneously in the apoptotic OHCs. In addition to caspase activation, noise exposure caused the release of cytochrome c from mitochondria, resulting in a punctate fluorescence in the cytosol. In contrast to activation of caspases, the release of cytochrome c took place in both apoptotic and necrotic OHCs. Moreover, the release of cytochrome c in a subpopulation of OHCs took place early in the cell death process, prior to any outward signs of necrosis or apoptosis. These data suggest that in this subpopulation there exists a common step that is shared by cell death pathways before entering either necrosis or apoptosis. Lastly, use of the TUNEL assay in combination with PI labeling provides a more accurate discrimination between apoptosis and necrosis.

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Temporal profile of cytochrome c and caspase-3 immunoreactivities and TUNEL staining after permanent middle cerebral artery occlusion in rats

Cited by 51 publications

References 0 publications

Stromal Cell-Derived Factor-1α Promotes Neuroprotection, Angiogenesis, and Mobilization/Homing of Bone Marrow-Derived Cells in Stroke Rats

Stromal Cell-Derived Factor-1α Promotes Neuroprotection, Angiogenesis, and Mobilization/Homing of Bone Marrow-Derived Cells in Stroke Rats

Cerebral Ischemia and Reperfusion: The Pathophysiologic Concept as a Basis for Clinical Therapy

The Caspase Pathway in Noise-Induced Apoptosis of the Chinchilla Cochlea

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