Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mice with a targeted disruption of the gene encoding the stilbene-insensitive electroneutral sodium bicarbonate cotransporter (NBC3; slc4a7) exhibit cochlear and retinal degeneration. To establish the progressive nature of sensory cells loss in slc4a7-/- deficient mice, we studied the morphology of cochleas of slc4a7-/- and slc4a7+/+ mice from postnatal day two (P2) to ninety (P90). Cell death was evaluated in slc4a7-/- cochleas using the TUNEL technique and caspase-3 immunoreactivity. The time course of NBC3 expression in the cochlea was assessed by immunohistochemistry using an antibody against NBC3. Between P2 and P8, slc4a7-/- mice cochlea exhibit normal morphology. There was a normal complement of inner and outer hair cells from the hook to the apical region. At P15, slc4a7-/- mice cochlea inner and outer hair cells were still present at the hook region, and vacuoles were seen underneath Hensen's cells. At P21, inner and outer hair cells were degenerated in this region. Between P30 and P90, there was a pronounced loss of hair cells and spiral ganglia neurons. Morphological analysis of the spiral ligament showed a progressive loss of type II and IV fibrocytes beginning at day 21. Transmission electron microscopy observations at P30 and P90 revealed that type II and IV fibrocytes showed shrinkage and vacuolization. In addition, hair cells were deteriorated with evidence of shrinkage and picnotic nuclei. TUNEL staining showed apoptotic cells at P8 in the organ of Corti at the basal region of the cochlea. At P15, caspase-3 immunoreactivity was present in supporting cells of the organ of Corti. NBC3 mild immunoreactivity was detected in the organ of Corti at P11. There was an increase in the expression of NBC3 in the spiral ligament between P17 and P19. From P21 to P90, NBC3 expression was confined to the spiral ligament and inner and outer sulcus cells. The vestibular sensory epithelia from slc4a7-/- mice were normal from P2 to P90. Damage of the sensory epithelia at the high frequency zone of the cochlea suggests that NBC3 may play an important physiological role in this region.
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PMID:Time course of auditory impairment in mice lacking the electroneutral sodium bicarbonate cotransporter NBC3 (slc4a7). 1618 86

To investigate if insulin-like growth factor-1 (IGF-1) provides neuroprotection to oligodendrocyte progenitor cells (OPCs) following cerebral hypoxia-ischemia, a previously developed neonatal rat model of white matter damage was used in this study. Postnatal day 4 (P4) SD rat pups were subjected to bilateral common carotid artery ligation, followed by exposure to 8% oxygen for 10 min. IGF-1 (0.5 microg) or vehicle was injected into the left ventricle after artery ligation and before the hypoxic exposure. Cerebral hypoxia-ischemia caused death of O4+ late OPCs in the P5 rat brain and impaired myelination in the P9 and P21 rat brain. Caspase-3 activation was involved in the death of OPCs. Moreover, cerebral hypoxia-ischemia impaired neurobehavioral performance in juvenile rats. IGF-1 treatment attenuated damages to OPCs and improved neurological functions after cerebral hypoxia-ischemia. It reduced death of O4+ OPCs by 39% on P5 and enhanced myelination on P9 and P21. Bromodeoxyuridine uptake assay showed that cerebral hypoxia-ischemia inhibited proliferation of stem/progenitor cells in the subventricular zone and NG2+ early OPCs in the white matter area. IGF-1 treatment increased cell proliferation in the subventricular zone by 31% 1 day following hypoxic-ischemic insult. Proliferation of early and late OPCs in the IGF-1-treated group was 1.5- and 2.4-fold of that in the vehicle-treated group, respectively. In conclusion, IGF-1 provided potent neuroprotection to OPCs and improved neurological functions following cerebral hypoxia-ischemia in the neonatal rat. The neuroprotection of IGF-1 was associated with its antiapoptotic and mitogenic effects.
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PMID:IGF-1 protects oligodendrocyte progenitor cells and improves neurological functions following cerebral hypoxia-ischemia in the neonatal rat. 1625 66

Photochemical internalization (PCI) technology has been used for PEI-mediated p53 gene transfer in mice bearing head and neck squamous cell carcinoma (HNSCC) xenografts. Using luciferase as a reporter gene, PCI led to a 20-fold increase in transgene expression 48 h after transfection and sustained transgene expression for 7 days. Therefore, iterative p53 gene transfer was performed by means of a weekly single injection of PEIGlu4/p53 complexes alone or with PCI for 5 (group A) or 7 (group B) weeks. The efficiency of p53 gene therapy was evaluated by following tumor growth and expression of P53-related downstream proteins (P21, MDM2, Bcl2, Bax). Apoptosis induction was evidenced through caspase-3 activation and PARP cleavage. Using PCI, tumor growth inhibition was observed in all transfected animals. Further, successful tumor cure was achieved in 17% (group A) and 83% (group B) of animals. PCI-mediated p53 gene transfer led to higher P53 protein expression that was correlated with induction of Bax and P21 proapoptotic proteins, repression of Bcl2 as well as activation of caspase-3, and cleavage of PARP. The present study demonstrates that PCI enhances the in vivo efficiency of PEI-mediated p53 gene transfer and can be proposed for p53 gene therapy in HNSCC.
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PMID:Eradication of p53-mutated head and neck squamous cell carcinoma xenografts using nonviral p53 gene therapy and photochemical internalization. 1656 29

Age-dependent, MK801-induced, activated caspase-3 expression in the postnatal brain is generally not observed in neurons expressing calcium-binding proteins (CaBPs), suggesting that apoptosis and calcium buffering are inversely related. In regions such as the cingulate and retrosplenial cortex, injury peaks at postnatal Day 7 (P7) and rapidly diminishes thereafter, whereas expression of calbindin (CB) and calretinin (CR) was relatively low from P0 to P7 and steadily increased from P7 to P14. At ages thereafter, CB and CR expression either remained stable then declined or rapidly declined. Parvalbumin (PV) was generally low-absent prior to P7 but expression dramatically increased from P10 onwards, peaking at P21. These studies suggest calcium entry (through N-methyl-D-aspartate receptor (NMDARs)) and buffering (by CaBPs) are integral to normal CNS maturation. Because schizophrenia is associated with glutamate hypo-function, developmental injury, and aberrant CaBP expression, our data indicate that this postnatal brain injury model may offer important insights into the nature of this disorder.
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PMID:Decline in age-dependent, MK801-induced injury coincides with developmental switch in parvalbumin expression: cingulate and retrosplenial cortex. 1768 Jun 8

Recent studies indicate that caspase-3 has distinct characteristics in postmitotic and neuronal progenitor apoptosis. Pyramidal neurons in CA1 and CA3 of the hippocampus become postmitotic during early postnatal development, whereas granule cells in the dentate gyrus (DG) undergo self-renewal throughout life. The distribution of caspase-3 in the hippocampal subfields during postnatal development is largely unknown. We used immunofluorescent staining for two isoforms of caspase-3 (an active 17 kDa isoform and an inactive 35 kDa precursor) and the Hoechst 33342 staining for nuclear chromatin to assess caspase-3 expression in the CA1, CA3, and DG of rat hippocampus during postnatal development. The expression of active caspase-3 reached a peak at P7 in CA1, at P2 in CA3, and then decreased with age. Whereas in DG, active caspase-3 expression increased slightly after P7, and remained at high levels for the rest of the investigated period. Procaspase-3 immunoreactivity was strong at P2 and decreased gradually to a basal plateau by P21 in the three regions examined. In addition, the number of apoptotic cells in the three regions all reached maximum levels at P7, and then decreased with age. These data indicate that there were specific spatio-temporal patterns of expression of active and precursor caspase-3 in the postnatally developing rat hippocampal subregions, and that the activation of caspase-3 in neuronal progenitor cells of DG and that in the postmitotic neurons of CA1 and CA3 may have distinct roles and mechanisms during postnatal development.
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PMID:Different expression of caspase-3 in rat hippocampal subregions during postnatal development. 1845 32

MK801-induced activation of caspase-3 is developmentally regulated, peaking at postnatal day (P) 7 and decreasing with increasing postnatal age thereafter. Further, at P7, cells displaying activation of caspase-3 lack expression of calcium binding proteins (CaBPs). To further explore this relationship, we investigated postnatal expression of calbindin (CB), calretinin (CR) and parvalbumin (PV) in two brain regions susceptible to MK801-induced injury, the somatosensory cortex (S1) and layer II/III of motor cortex (M1/M2). Expression of CB and especially PV was low to absent prior to P7 but substantially increased from P7 through to P21 and adulthood. In contrast, CR expression was more variable at early developmental ages, stabilized to lower levels after P7 and showed a marked decline by P21. The results suggest that not only does calcium buffering capacity increase developmentally but also acquisition of enhanced buffering may be one mechanism by which neurons survive agent-induced alterations in calcium homeostasis.
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PMID:Decline in age-dependent, MK801-induced injury coincides with developmental switch in parvalbumin expression: somatosensory and motor cortex. 1868 10

Our goals were to examine the dual-directional regulation effects of resveratrol (1) in vitro by using MCF-7 cells (estradiol receptor-positive cells), study its mechanism of action, and give a systematical analysis of the regulatory networks of each related factor. An MTT test and growth curve showed that the proliferation of MCF-7 cells was inhibited by a high concentration of 1, and that its IC(50) was 8.70 x 10(-5) +/- 0.23 mol/l. However, 1 induced the proliferation of MCF-7 cells at 10(-7)-10(-5) mol/l, and resulted in a peak proliferation at 1.0 x 10(-7) mol/l. A high concentration of 1 arrested cell cycle progression at the G(1) phase, and a typical "sub-G(1) peak" of apoptotic cells was also observed by flow cytometry. The proliferation index of MCF-7 cells increased significantly with a low concentration of 1 (p < 0.05). 1 in high concentrations induced Bax, caspase-3, and cyclin-dependent kinase (CDK) inhibitor P21 expression, whereas the expressions of cyclin CDK2, Bcl-2, and proliferating cell nuclear antigen (PCNA) were decreased by 1 treatment. Conversely, treatment with low concentrations of 1 decreased the expression of P21 and Bax, while the expressions of cyclin CDK2, Bcl-2, and PCNA were increased. These results suggest that 1 had a dual-regulatory effect on MCF-7 cells. CDK-associated protein was a key factor at both the high and low concentrations used in this study.
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PMID:Effect of proliferation, cell cycle, and Bcl-2s of MCF-7 cells by resveratrol. 1943 Oct 20

To investigate the effect of proteasomes reactivator REG gamma on cell cycle and apoptosis in vitro and in vivo. In vitro, we first constructed recombinant plasmid of PcDNA3.1-REGgamma and then transfected REGgamma into MDA-MB-231 cell line. We confirmed the transfection efficiency by Western blot. Subsequently, we observed cell growth, cycle and colony formation. Specific proliferative molecule proliferating cell nuclear antigen (PCNA) and apoptosis related signal molecule Caspase-3 was assayed by immmunohistochemistry and absorption spectrometry, respectively. In vivo, we successfully established transplantation tumor nude mice model. We determined REGgamma mRNA level in the transplantation tumor tissue. Then, FCM was used to determine cell cycle, apoptosis and CD16. Finally, we employed immunohistochemistry to determine P21 positive expression. However, the cells transfected with REGgamma grew more rapidly compared with non-transfected ones. Increased cells were observed in S+G2+M phase and S phase in the REGgamma transfected group. PCNA expression level in the transfected cells was higher than that in non-transfected ones. In vivo, we observed the similar phenomenon including more rapid tumor growth, higher REGgamma mRNA expression, decreased cells number in G0/G1 phase and G2/M phase, increased cells in S phase and decreased apoptosis in the transfected group. In the study of related molecules, we also found related molecules P21 and CD16 positive expression rate were obviously lower than non-infected ones. In present study, we found oncogenicity of MDA-MB-231 cell transfected with REGgamma was enhanced, which might be realized via REGgamma promoting cell growth, inhibiting cell apoptosis, degrading P21 and suppressing activation of NK, suggesting REGgamma promoting tumor growth is a process involving multiple factor mechanisms.
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PMID:Proteasomes reactivator REG gamma enchances oncogenicity of MDA-MB-231 cell line via promoting cell proliferation and inhibiting apoptosis. 1965 65

It is well-known that zinc deficiency leads to neuronal death in the brain. Here we tested the hypothesis that changes in the TrkB signaling pathway are involved in hippocampal neuronal apoptosis of suckling offspring with maternal zinc deficiency. Postpartum mice were fed a zinc-deficient (0.85 ppm) diet and their offspring were used as a lactational zinc deficiency mouse model. At P7, P14, and P21, changes in hippocampal neuronal apoptosis were assessed by Nissl and TUNEL staining. BDNF levels and TrkB neurotrophic signaling were examined using immunoblotting assay. Lactational zinc deficiency resulted in lower levels of p-TrkB and p-ERK, and higher levels of Bax/Bcl-2 and caspase-3 in the hippocampus, suggesting that zinc deficiency-induced low levels of TrkB phosphorylation would abrogate the downstream ERK signaling pathway, leading to hippocampal neuronal apoptosis. Most interestingly, our data showed that the activity of Src, a key molecule for zinc-induced TrkB activation through the BDNF-independent pathway, was inhibited significantly, and the expression levels of BDNF were significantly increased in the hippocampus of suckling mice. The present data indicate that zinc depletion-induced hippocampal neuronal apoptosis is likely through modulation of the TrkB neurotrophic signaling pathway by a BDNF-independent and Src-dependent mechanism, whereas higher expression of BDNF is considered as a protective response, which cannot fully compensate for the injury caused by maternal zinc deficiency.
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PMID:Lactational zinc deficiency-induced hippocampal neuronal apoptosis by a BDNF-independent TrkB signaling pathway. 2010 2

Interleukin-24 (IL-24)/melanoma differentiation associated gene-7 (mda-7) as a novel tumor-suppressor gene has potent antitumor activities in a broad spectrum of human cancers through the activation of various signaling pathways. However, the suppressive effect of adenovirus-mediated IL-24 (Ad-IL-24) expression on human laryngeal cancers is still elusive. In this study, we explored the therapeutic effect of Ad-IL-24 on human laryngeal cancers in vitro and in vivo in an athymic nude mouse model, using a Hep-2 human laryngocarcinoma cell line, and a WI-38 human diploid cell line served as a normal cell control. We demonstrated that Ad-IL-24 induced significant growth inhibition and apoptosis, upregulated the expression of P21, P27, and Bax, downregulated Bcl-2 expression, and activated caspase-3 in Hep-2 laryngeal tumor cells, while it exerted no direct effect on the in vitro proliferation of WI-38 normal diploid cells. Moreover, intratumoral injections of Ad-IL-24 in nude mice bearing Hep-2 tumors significantly suppressed the laryngeal xengrafted tumor growth and reduced microvessel density (MVD) and VEGF expression in tumors. This retarded tumor growth in vitro and in vivo elicited by Ad-IL-24 was closely associated with the upregulation of proliferation-related molecules P21 and P27, decrease in the ratio of anti- to proapoptotic molecules Bcl-2/Bax, followed by the activation of caspase-3, leading to apoptosis via intrinsic apoptotic pathways, and the reduced expression of proangiogenic factor VEGF involved in the inhibition of tumor angiogenesis. Thus, our results indicate that the potent, selective killing activity of Ad-IL-24 in laryngeal cancer cells, but not in normal cells, makes this vector a potential candidate for laryngeal cancer gene therapy.
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PMID:The in vitro and in vivo antitumor activity of adenovirus-mediated interleukin-24 expression for laryngocarcinoma. 2018 94


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