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1.
J Exp Med ; 214(2): 423-437, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28082356

RESUMO

Inhibition of the IκB kinase complex (IKK) has been implicated in the therapy of several chronic inflammatory diseases including inflammatory bowel diseases. In this study, using mice with an inactivatable IKKα kinase (IkkαAA/AA), we show that loss of IKKα function markedly impairs epithelial regeneration in a model of acute colitis. Mechanistically, this is caused by compromised secretion of cytoprotective IL-18 from IKKα-mutant intestinal epithelial cells because of elevated caspase 12 activation during an enhanced unfolded protein response (UPR). Induction of the UPR is linked to decreased ATG16L1 stabilization in IkkαAA/AA mice. We demonstrate that both TNF-R and nucleotide-binding oligomerization domain stimulation promote ATG16L1 stabilization via IKKα-dependent phosphorylation of ATG16L1 at Ser278. Thus, we propose IKKα as a central mediator sensing both cytokine and microbial stimulation to suppress endoplasmic reticulum stress, thereby assuring antiinflammatory function during acute intestinal inflammation.


Assuntos
Proteínas de Transporte/metabolismo , Quinase I-kappa B/fisiologia , Inflamação/metabolismo , Animais , Proteínas Relacionadas à Autofagia , Proteínas de Transporte/química , Caspase 12/fisiologia , Colite/prevenção & controle , Estresse do Retículo Endoplasmático , Endorribonucleases/fisiologia , Interleucina-18/metabolismo , Camundongos , NF-kappa B/fisiologia , Proteína Adaptadora de Sinalização NOD2/fisiologia , Proteínas Serina-Treonina Quinases/fisiologia , Estabilidade Proteica , Resposta a Proteínas não Dobradas
2.
J Immunol ; 196(1): 437-47, 2016 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-26582949

RESUMO

Inflammation is well established to significantly impact metabolic diseases. The inflammatory protease caspase-1 has been implicated in metabolic dysfunction; however, a potential role for the related inflammatory caspases is currently unknown. In this study, we investigated a role for caspase-11 and caspase-12 in obesity and insulin resistance. Loss of caspase-12 in two independently generated mouse strains predisposed mice to develop obesity, metabolic inflammation, and insulin resistance, whereas loss of caspase-11 had no effect. The use of bone marrow chimeras determined that deletion of caspase-12 in the radio-resistant compartment was responsible for this metabolic phenotype. The Nlrp3 inflammasome pathway mediated the metabolic syndrome of caspase-12-deficient mice as ablation of Nlrp3 reversed Casp12(-/-) mice obesity phenotype. Although the majority of people lack a functional caspase-12 because of a T(125) single nucleotide polymorphism that introduces a premature stop codon, a fraction of African descendents express full-length caspase-12. Expression of caspase-12 was linked to decreased systemic and adipose tissue inflammation in a cohort of African American obese children. However, analysis of the Dallas Heart Study African American cohort indicated that the coding T(125)C single nucleotide polymorphism was not associated with metabolic parameters in humans, suggesting that host-specific differences mediate the expressivity of metabolic disease.


Assuntos
Caspase 12/fisiologia , Caspases/fisiologia , Resistência à Insulina/genética , Obesidade/genética , Animais , Proteínas de Transporte/genética , Proteínas de Transporte/imunologia , Caspase 12/genética , Caspases/genética , Caspases Iniciadoras , Intolerância à Glucose/genética , Humanos , Inflamação/genética , Inflamação/imunologia , Masculino , Camundongos , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR , Polimorfismo de Nucleotídeo Único/genética , Proteína Serina-Treonina Quinase 2 de Interação com Receptor , Proteína Serina-Treonina Quinases de Interação com Receptores/genética
3.
Exp Gerontol ; 70: 61-70, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26173054

RESUMO

Endoplasmic reticulum (ER) stress triggers the unfolded protein response (UPR) to prevent the accumulation of proteins in an aberrant conformation. The UPR can restore homeostasis by upregulating ER chaperones, such as glucose-regulated protein 78kD (GRP78), to refold the incorrectly handled protein, and by degrading the misfolded proteins via the ubiquitin-proteasome and autophagy-lysosome system. ER stress was recently demonstrated to be involved in the pathogenesis of age-related diseases. In this study, we measured the expression levels of GRP78 and ubiquitinated proteins in the cochleae of young C57BL/6 mice and aged mice to assess the capacity of the UPR. The lower expression of GRP78 and the increased number of ubiquitinated proteins observed in the cochleae of aged mice suggested that the capacity of the UPR was impaired and that the cell death pathway was activated. We found a markedly increased expression of the ER-related pro-apoptotic factor C/EBP homologous protein (CHOP) in the cochleae of aged mice, whereas the level of cleaved caspase-12 did not differ between the two groups. In addition, the cleavage of caspase-9, caspase-3 and poly [ADP-ribose] polymerase 1 was significantly increased in the aged cochleae, suggesting the activation of apoptosis in the cochleae resulting from the cross-talk between the ER and mitochondria through CHOP. These results indicated that impaired UPR in the cochleae of aged C57BL/6 mice resulting in ER stress may lead to apoptosis that is dependent on the mitochondrial pathway and that ER stress induced apoptosis may not be mediated by caspase-12.


Assuntos
Envelhecimento/metabolismo , Cóclea/metabolismo , Perda Auditiva/metabolismo , Resposta a Proteínas não Dobradas/fisiologia , Envelhecimento/patologia , Envelhecimento/fisiologia , Animais , Apoptose/fisiologia , Caspase 12/fisiologia , Caspase 3/fisiologia , Cóclea/patologia , Cóclea/fisiopatologia , Modelos Animais de Doenças , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático/fisiologia , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Perda Auditiva/patologia , Perda Auditiva/fisiopatologia , Proteínas de Choque Térmico/metabolismo , Camundongos Endogâmicos C57BL , Limiar Sensorial/fisiologia
4.
PLoS One ; 7(5): e37022, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22615879

RESUMO

BACKGROUND: Caspase-12 (CASP12) modulates the susceptibility to sepsis. In humans, the "C" allele at CASP12 rs497116 has been associated with an increased risk of sepsis. Instead, the derived "T" allele encodes for an inactive caspase-12. Interestingly, Eurasians are practically fixed for the inactive variant, whereas in Sub-Saharan Africa the active variant is still common (~24%). This marked structure has been explained as a function of the selective advantage that the inactive caspase-12 confers by increasing resistance to infection. As regards to both when positive selection started acting and as to the speed with which fixation was achieved in Eurasia, estimates depend on the method and assumptions used, and can vary substantially. Using experimental evidence, we propose that, least in Eurasia, the increase in the frequency of the T allele might be related to the selective pressure exerted by the increase in zoonotic diseases transmission caused by the interplay between increased human population densities and a closer contact with animals during the Neolithic. METHODOLOG/PRINCIPAL FINDINGS: We genotyped CASP12 rs497116 in prehistoric individuals from 6 archaeological sites from the North of the Iberian Peninsula that date from Late Upper Paleolithic to Late Neolithic. DNA extraction was done from teeth lacking cavities or breakages using standard anti-contamination procedures, including processing of the samples in a positive pressure, ancient DNA-only chamber, quantitation of DNAs by qPCR, duplication, replication, genotyping of associated animals, or cloning of PCR products. Out of 50, 24 prehistoric individuals could finally be genotyped for rs497116. Only the inactive form of CASP12 was found. CONCLUSIONS/SIGNIFICANCE: We demonstrate that the loss of caspase-12 in Europe predates animal domestication and that consequently CASP12 loss is unlikely to be related to the impact of zoonotic infections transmitted by livestock.


Assuntos
Caspase 12/fisiologia , Alelos , Caspase 12/genética , Europa (Continente) , Genética Populacional , Genótipo , História Antiga , Humanos , Sepse/enzimologia , Sepse/genética
5.
Neurosci Lett ; 478(1): 32-6, 2010 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-20444431

RESUMO

Astrocytes play an important role in protecting neurons during ischemia and reperfusion in the central nervous system. Although many studies have shown that oxygen-glucose deprivation (OGD) can induce astrocyte apoptosis, the role of PERK/eIF2 alpha/ATF4 integrated stress response (ISR) in astrocyte apoptosis mediated by oxygen-glucose-serum deprivation (OGSD)/restoration remains uncertain. Astrocytes were subjected to a combination of oxygen, glucose, and serum deprivation for 8h followed by restoration. Hoechst 33342 staining was performed to quantify apoptotic astrocytes and cell viability was assessed with Cell Counting Kit-8 (CCK8). Immunocytochemical analysis and Western blotting for some related molecules, including pancreatic ER stress kinase (PERK), p-PERK, eukaryotic initiation factor 2 alpha (eIF2 alpha), p-eIF2 alpha, activating transcription factor 4 (ATF4), caspase-12, were examined. Caspase activation and apoptosis were detected in neonatal rat astrocytes from spinal cord subjected to OGSD/restoration. We also observed an increase in cytoplasmic staining of p-eIF2 alpha in astrocytes (8h OGSD/15 min restoration) compared with that of non-treated cells. In addition, we found the sequential activation of PERK, eIF2 alpha, and ATF4 during OGSD/restoration by Western blotting. These results indicate that both the PERK/eIF2 alpha/ATF4 ISR and activation of caspase-12 may be involved in apoptosis of spinal cord astrocytes induced by OGSD/restoration.


Assuntos
Apoptose , Astrócitos/citologia , Caspase 12/fisiologia , Fator de Iniciação 2 em Eucariotos/fisiologia , Glucose/deficiência , Oxigênio/metabolismo , Medula Espinal/citologia , Fator 4 Ativador da Transcrição/fisiologia , Animais , Animais Recém-Nascidos , Astrócitos/metabolismo , Sobrevivência Celular , Células Cultivadas , Meios de Cultura Livres de Soro , Ativação Enzimática , Ratos , Ratos Sprague-Dawley , Medula Espinal/metabolismo , eIF-2 Quinase/fisiologia
6.
PLoS One ; 4(9): e6870, 2009 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-19721713

RESUMO

BACKGROUND: Caspase-12 functions as an antiinflammatory enzyme inhibiting caspase-1 and the NOD2/RIP2 pathways. Due to increased susceptibility to sepsis in individuals with functional caspase-12, an early-stop mutation leading to the loss of caspase-12 has replaced the ancient genotype in Eurasia and a significant proportion of individuals from African populations. In African-Americans, it has been shown that caspase-12 inhibits the pro-inflammatory cytokine production. METHODOLOGY/PRINCIPAL FINDINGS: We assessed whether similar mechanisms are present in African individuals, and whether evolutionary pressures due to plague may have led to the present caspase-12 genotype population frequencies. No difference in cytokine induction through the caspase-1 and/or NOD2/RIP2 pathways was observed in two independent African populations, among individuals with either an intact or absent caspase-12. In addition, stimulations with Yersinia pestis and two other species of Yersinia were preformed to investigate whether caspase-12 modulates the inflammatory reaction induced by Yersinia. We found that caspase-12 did not modulate cytokine production induced by Yersinia spp. CONCLUSIONS: Our experiments demonstrate for the first time the involvement of the NOD2/RIP2 pathway for recognition of Yersinia. However, caspase-12 does not modulate innate host defense against Y. pestis and alternative explanations for the geographical distribution of caspase-12 should be sought.


Assuntos
Caspase 12/fisiologia , Regulação da Expressão Gênica , Sepse/metabolismo , Yersiniose/metabolismo , Yersinia pestis/patogenicidade , Citocinas/metabolismo , Genótipo , Humanos , Imunidade Inata , Inflamação , Interleucina-1beta/metabolismo , Mali , Proteína Adaptadora de Sinalização NOD2/metabolismo , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/metabolismo
7.
Int J Dev Neurosci ; 25(7): 455-63, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17913437

RESUMO

In the present study, we have found evidence for ER stress occurring during development of the central nervous system in the mouse. Several ER-resident stress-regulated chaperones, such as calreticulin, glucose regulated protein 78, glucose regulated protein 94, ER protein 57 and protein disulfide isomerase, were expressed at higher levels in embryonic brain and retina, compared with adult tissues. In contrast, calnexin, a chaperone that is not regulated by stress was equally abundant in embryonic and adult tissues. We also detected unfolded protein response during embryonic development. Both eukaryotic translation initiation factor 2 alpha and its phosphorylated form were more abundant in embryonic brain and retina than in adult tissues. Spliced X-box binding protein-1 mRNA was detected in embryonic brain and retina, while it was absent in adult counterparts. Partially glycosylated form of activating transcription factor 6 alpha, another ER stress indicator, was detected predominantly in embryonic brain. Finally, apoptotic pathway components, caspase-7 and -12, were more abundant in embryonic brain than in adult. The pattern of expression of chaperones together with activation of the unfolded protein response factors suggests the presence of ER stress during development of brain and retina. Furthermore, our data suggest that ER stress-like mechanism may induce apoptosis via activation of the caspases during embryonic development of the central nervous system.


Assuntos
Sistema Nervoso Central/embriologia , Retículo Endoplasmático/fisiologia , Estresse Fisiológico/fisiopatologia , Animais , Apoptose/fisiologia , Western Blotting , Química Encefálica/fisiologia , Calnexina/metabolismo , Calreticulina/metabolismo , Caspase 12/metabolismo , Caspase 12/fisiologia , Caspase 7/metabolismo , Caspase 7/fisiologia , Células Cultivadas , Sistema Nervoso Central/metabolismo , Ativação Enzimática/fisiologia , Feminino , Imunofluorescência , Marcação In Situ das Extremidades Cortadas , Camundongos , Proteínas do Tecido Nervoso/biossíntese , Gravidez , Dobramento de Proteína , Retina/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/fisiologia
8.
Apoptosis ; 12(11): 1979-88, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17828455

RESUMO

Previous studies have demonstrated that arachidonic acid (AA) metabolites released by the cyclooxygenase pathway is involved in serum-induced 3T6 fibroblast cycle progression and proliferation. However, these results also suggest that other AA cascade pathways might be involved. Recently, we also described the role of hydroxyeicosatetraenoic acids, which are produced by cytochrome P450 monooxygenases (CYP), in 3T6 fibroblast growth. AA can be also metabolized by the epoxygenase activity of CYP-producing epoxyeicosatrienoic acids (EETs). Finally, the cytosolic epoxide hydrolases catalyze the hydration of the EETs, transforming them into dihydroxyeicosatetraenoic acids (DHETEs). In this work, we have studied the role of the EETs/DHETEs on 3T6 fibroblasts growth. Our results show that PDGF stimulates 3T6 fibroblast proliferation and [3H]thymidine incorporation, while the addition of 5,6-EET, 8,9-EET, 11,12-EET or 14,15-EET (0.1-1 microM) inhibit these processes. Furthermore, 5,6-DHETE and 11,12-DHETE (0.1-1 microM) also inhibit cell proliferation and DNA synthesis. Interestingly, this growth inhibition was correlated with an induction of apoptosis. Thus, we observed that in the presence of PDGF, EETs or DHETEs (0.1-1 microM) induce phosphatidylserine externalization (as measured by annexin V-binding) and DNA fragmentation (as quantified using a TUNEL assay). Our results show that calpain, as well as caspase-12 and caspase-3, are involved in these events. Therefore, EETs and DHETEs have anti-proliferative and pro-apoptotic effects on PDGF-stimulated 3T6 fibroblasts.


Assuntos
Apoptose/fisiologia , Ácidos Araquidônicos/fisiologia , Calpaína/fisiologia , Caspase 12/fisiologia , Fibroblastos/metabolismo , Inibidores do Crescimento/fisiologia , Fator de Crescimento Derivado de Plaquetas , Animais , Linhagem Celular , Replicação do DNA/fisiologia , Camundongos
9.
J Pharmacol Sci ; 104(1): 46-55, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17452809

RESUMO

Amyloid beta (Abeta) toxicity has been implicated in cell death in the hippocampus, but its specific mechanisms are poorly understood. In this study, Abeta-induced cell death was investigated in organotypic hippocampal slice cultures (OHCs) that were cultured for various periods in vitro. There were no obvious histological differences among slices cultured for 3 to 7 weeks in vitro. Although there was little neurotoxicity after treatment with Abeta25-35 in OHCs cultured for relatively shorter periods (3-5 weeks), age-dependent cell death was evident in OHCs cultured for relatively longer periods (6-7 weeks) after exposure to Abeta25-35. In OHCs cultured for 7 weeks, S-allyl-L-cysteine (SAC), a component of aged garlic extract, protected the cells in areas CA1 and CA3 and the dentate gyrus from Abeta25-35-induced toxicity. The immunoreactivity of cleaved caspase-12 was increased whereas that of glucose-regulated protein 78 was not altered after exposure to Abeta25-35. The increases in the cleaved caspase-12 were also reversed by simultaneously applied SAC. These results suggest that OHCs cultured for relatively longer periods are more susceptible to Abeta-induced toxicity and that the Abeta-induced cell death involves caspase-12-dependent pathways. It is also suggested that SAC is able to protect against the Abeta-induced neuronal cell death through the inhibition of the caspase-12-dependent pathway.


Assuntos
Peptídeos beta-Amiloides/farmacologia , Caspase 12/metabolismo , Giro Denteado/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Animais , Western Blotting , Caspase 12/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Cisteína/análogos & derivados , Cisteína/farmacologia , Giro Denteado/patologia , Relação Dose-Resposta a Droga , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/enzimologia , Chaperona BiP do Retículo Endoplasmático , Agonistas de Aminoácidos Excitatórios/farmacologia , Proteínas de Choque Térmico/metabolismo , Ácido Ibotênico/farmacologia , L-Lactato Desidrogenase/metabolismo , Chaperonas Moleculares/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/patologia , Técnicas de Cultura de Órgãos , Ratos , Ratos Wistar , Fatores de Tempo
10.
J Neurochem ; 101(4): 889-97, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17394578

RESUMO

The unfolded protein response (UPR) is implicated in many neurodegenerative disorders including Alzheimer, Parkinson and prion diseases, and the leukodystrophy, Pelizaeus-Merzbacher disease (PMD). Critical features of degeneration in several of these diseases involve activation of cell death pathways in various neural cell populations, and the initiator caspase 12 has been proposed to play a central role. Accordingly, pharmacological strategies to inhibit caspase 12 activity have received remarkable attention in anticipation of effecting disease amelioration. Our investigation in animal models of PMD demonstrates that caspase 12 is activated following accumulation of mutant proteins in oligodendrocytes; however, eliminating caspase 12 activity does not alter pathophysiology with respect to levels of apoptosis, oligodendrocyte function, disease severity or life span. We conclude that caspase 12 activation by UPR signaling is an epiphenomenon that plays little discernable role in the loss of oligodendrocytes in vivo and may portend the inconsequence of caspase 12 to the pathophysiology of other protein conformational diseases.


Assuntos
Caspase 12/fisiologia , Oligodendroglia/enzimologia , Dobramento de Proteína , Animais , Animais Recém-Nascidos , Células COS , Caspase 12/deficiência , Caspase 9/metabolismo , Chlorocebus aethiops , Modelos Animais de Doenças , Ativação Enzimática/genética , Marcação In Situ das Extremidades Cortadas/métodos , Longevidade/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Atividade Motora/genética , Proteína Proteolipídica de Mielina/deficiência , Proteína Proteolipídica de Mielina/genética , Proteínas do Tecido Nervoso/deficiência , Proteínas do Tecido Nervoso/genética , Doença de Pelizaeus-Merzbacher/genética , Doença de Pelizaeus-Merzbacher/patologia
11.
Sheng Li Xue Bao ; 58(5): 463-70, 2006 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-17041731

RESUMO

Calreticulin (CRT), an important Ca(2+)-binding molecular chaperone in the endoplasmic reticulum (ER), and caspase-12, a pivotal molecule mediating ER-initiated apoptosis, are involved in the ER stress (ERS). Using primary cultured neonatal cardiomyocytes, CRT and caspase-12 expression and activation during hypoxic preconditioning (HPC) and hypoxia/reoxygenation (H/R) were studied to explore the role of ERS in cardioprotection by HPC. And by using SB203580 and SP600125 [the specific inhibitors of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK)] separately, the role of p38 MAPK in HPC-induced ERS was also detected. Neonatal cardiomyocytes were prepared from Sprague-Dawley rats aged 24 h, and cultured in DMEM medium containing 10% fetal bovine serum, and then randomly divided into six groups as follows: H/R, HPC+H/R, SB203580+HPC+H/R, SP600125+HPC+H/R, HPC and control groups. H/R was produced by 2-hour hypoxia/14-hour reoxygenation, and HPC by 20-minute hypoxia/24-hour reoxygenation. Morphological studies, estimation of lactate dehydrogenase (LDH) leakage and flow cytometry were employed to assess cell apoptosis and necrosis. CRT and caspase-12 expression and activation, levels of phospho-p38 MAPK and phospho-JNK were detected by Western blot. All experiments were repeated at least four separate times. The results obtained are as follows: (1) HPC relieved the cell injury caused by H/R. Compared with that in H/R group, cellso survival rate in HPC+H/R group increased by 6.4%, and the apoptosis rate and LDH leakage in the cell culture medium decreased by 6.6% and 70.0%, respectively. (2) H/R induced caspase-12 activation (33.2-fold increase in comparison with control) and CRT expression (8.1-fold increase in comparison with control). HPC itself resulted in mild CRT up-regulation (2.6-fold increase in comparison with control), but the extent of up-regulation was lower than that induced by H/R. HPC before H/R was found to relieve the over-expression of CRT induced by H/R (72.4% decrease), and to inhibit the activation of caspase-12 (59.6% decrease). (3) The protection of HPC and HPC-induced up-expression of CRT and inhibition of caspase-12 activation were almost eliminated when the inhibitor of p38 MAPK, not of JNK, was present before HPC. These results suggest that HPC protects the neonatal cardiomyocytes from severe ERS-induced apoptosis during sustained H/R through pre-invoking proper ERS response. Mild up-expression of CRT and inhibition of caspase-12 activation induced by HPC, which are important protection factors, are mediated by p38 MAPK, not by JNK.


Assuntos
Retículo Endoplasmático/metabolismo , Precondicionamento Isquêmico Miocárdico , Proteínas Quinases p38 Ativadas por Mitógeno/fisiologia , Animais , Caspase 12/fisiologia , Hipóxia Celular , Citoproteção , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Ratos , Ratos Sprague-Dawley
12.
Apoptosis ; 11(9): 1629-41, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16820963

RESUMO

Co-activation and cross-talk of different apoptotic pathways have been described in several systems however, the differential contributions of the different executors have not been well characterized. Here we report the co-translocation to the nucleus of caspase-12 and AIF in response to two endoplasmic reticulum (ER) stresses: protein misfolding and disruption of calcium homeostasis. As seen by treatment with pan-caspase inhibitor and calpain inhibitors, apoptosis is not mediated by executor caspases but by calpains. By reduction of AIF or caspase-12 expression we unraveled that AIF primarily controls apoptosis caused by changes in calcium homeostasis while caspase-12 has a main role in programmed cell death induced by protein misfolding. Nevertheless, the two apoptotic factors appear to reinforce each other during the apoptotic process, confirming that while the first response primarily involves one organelle, mitochondria and ER can influence each other in the apoptotic event.


Assuntos
Fator de Indução de Apoptose/fisiologia , Apoptose/fisiologia , Caspase 12/fisiologia , Retículo Endoplasmático/fisiologia , Receptor Cross-Talk/fisiologia , Transdução de Sinais/fisiologia , Animais , Fator de Indução de Apoptose/metabolismo , Cálcio/metabolismo , Bloqueadores dos Canais de Cálcio/farmacologia , Caspase 12/metabolismo , Retículo Endoplasmático/efeitos dos fármacos , Camundongos , Mitocôndrias/metabolismo , Modelos Biológicos , Células NIH 3T3 , Dobramento de Proteína , Transporte Proteico/fisiologia , Interferência de RNA , Tapsigargina/efeitos adversos , Tapsigargina/farmacologia , Distribuição Tecidual , Transfecção , Tunicamicina/efeitos adversos , Tunicamicina/farmacologia
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