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1.
Int. j. morphol ; 40(6): 1574-1578, dic. 2022. ilus, tab
Article Dans Anglais | LILACS | ID: biblio-1421819

Résumé

SUMMARY: Cadmium is a highly toxic metal and affects the respiratory mucosa. The aim of the study is to show the inflammation and degenerative effect of cadmium on the olfactory mucosa. In this study, eight-week-old Wistar rats with an average weight of 170-190 g were divided into two groups (control and experiment) with 20 animals in each group and used in the experiments. The rats in the experimental group were given 2 mg/kg/day powdered cadmium chloride dissolved in water intraperitoneally every day for two weeks. At the end of the experiment, the nasal cavity was completely removed with anesthesia. Concha nasalis superior was separated, fixed with zinc-Formalin solution and decalcified with 5 % EDTA (Ethylene-diaminetetraacetic acid). After routine histopathological procedure, APAF-1 antibody was used for expression of Hematoxylin-Eosin (HE) and immunohistochemistry. Histopathological examination revealed interruptions in the basement membrane structure due to cadmium and degenerative changes in stem cells, degeneration in sensory cells and pycnosis in nuclei, dilatation in blood vessels and increased inflammation in connective tissue. APAF-1 expression was found to increase in epithelial cells and olfactory glands (Bowman gland) cells. It has been thought that cadmium toxicity increases cell degeneration and inflammation in the olfactory mucosa and may significantly affect cell death and olfactory metabolism by inducing the pro-apoptotic process.


El cadmio es un metal altamente tóxico que afecta la mucosa respiratoria. El objetivo fue mostrar el efecto inflamatorio y degenerativo del cadmio sobre la mucosa olfativa. En este estudio, ratas Wistar de ocho semanas de edad con un peso promedio de 170-190 g se dividieron en dos grupos (control y experimental) con 20 animales en cada grupo. Las ratas del grupo experimental recibieron 2 mg/kg/día de cloruro de cadmio en polvo disuelto en agua por vía intraperitoneal todos los días durante dos semanas. En los animales se exirpó la cavidad nasal bajo anestesia. Se separó la concha nasal superior, se fijó con solución de zinc-Formalina y se descalcificó con EDTA (ácido etilendiaminotetraacético) al 5 %. Después del procedimiento histopatológico de rutina, Hematoxilina- Eosina (HE) e inmunohistoquímica, se utilizó el anticuerpo APAF-1. El examen histopatológico reveló interrupciones en la estructura de la membrana basal debido al cadmio y cambios degenerativos en las células madre, degeneración en las células sensoriales y picnosis en los núcleos, dilatación de los vasos sanguíneos y aumento de la inflamación en el tejido conjuntivo. Se encontró que la expresión de APAF-1 aumenta en las células epiteliales y en las células de las glándulas olfatorias (glándulas de Bowman). Se ha pensado que la toxicidad del cadmio aumenta la degeneración celular y la inflamación en la mucosa olfativa y puede afectar significativamente la muerte celular y el metabolismo olfativo al inducir el proceso proapoptótico.


Sujets)
Animaux , Rats , Muqueuse olfactive/effets des médicaments et des substances chimiques , Muqueuse olfactive/anatomopathologie , Chlorure de cadmium/toxicité , Administration par voie nasale , Immunohistochimie , Rat Wistar , Facteur-1 activateur des protéases apoptotiques
2.
Braz. j. med. biol. res ; 54(2): e9017, 2021. graf
Article Dans Anglais | LILACS, ColecionaSUS | ID: biblio-1142574

Résumé

The purpose of this study was to investigate the anti-cancer effect of melittin on growth, migration, invasion, and apoptosis of non-small-cell lung cancer (NSCLC) cells. This study also explored the potential anti-cancer mechanism of melittin in NSCLC cells. The results demonstrated that melittin suppressed growth, migration, and invasion, and induced apoptosis of NSCLC cells in vitro. Melittin increased pro-apoptotic caspase-3 and Apaf-1 gene expression. Melittin inhibited tumor growth factor (TGF)-β expression and phosphorylated ERK/total ERK (pERK/tERK) in NSCLC cells. However, TGF-β overexpression (pTGF-β) abolished melittin-decreased TGF-β expression and pERK/tERK in NSCLC cells. Treatment with melittin suppressed tumor growth and prolonged mouse survival during the 120-day observation in vivo. Treatment with melittin increased TUNEL-positive cells and decreased expression levels of TGF-β and ERK in tumor tissue compared to the control group. In conclusion, the findings of this study indicated that melittin inhibited growth, migration, and invasion, and induced apoptosis of NSCLC cells through down-regulation of TGF-β-mediated ERK signaling pathway, suggesting melittin may be a promising anti-cancer agent for NSCLC therapy.


Sujets)
Animaux , Lapins , Apoptose , Carcinome pulmonaire non à petites cellules/génétique , Carcinome pulmonaire non à petites cellules/traitement médicamenteux , Système de signalisation des MAP kinases , Tumeurs du poumon/génétique , Tumeurs du poumon/traitement médicamenteux , Mélittine/pharmacologie , Régulation négative , Régulation de l'expression des gènes tumoraux , Mouvement cellulaire , Facteur de croissance transformant bêta/métabolisme , Lignée cellulaire tumorale , Caspase-3 , Facteur-1 activateur des protéases apoptotiques , Invasion tumorale
3.
Braz. j. med. biol. res ; 52(11): e8772, 2019. graf
Article Dans Anglais | LILACS | ID: biblio-1039259

Résumé

This study aimed to investigate the mechanism of fluorofenidone (AKF-PD) in treating renal interstitial fibrosis in rats with unilateral urinary obstruction (UUO). Thirty-two male Sprague-Dawley rats were randomly divided into sham, UUO, UUO + enalapril, and UUO + AKF-PD groups. All rats, except sham, underwent left urethral obstruction surgery to establish the animal model. Rats were sacrificed 14 days after surgery, and serum was collected for renal function examination. Kidneys were collected to observe pathological changes. Immunohistochemistry was performed to assess collagen I (Col I) protein expression, and terminal deoxynucleotidyl transferase-mediated nick end-labeling staining to observe the apoptosis of renal tubular epithelial cells. The expression of Fas-associated death domain (FADD), apoptotic protease activating factor-1 (Apaf-1), and C/EBP homologous protein (CHOP) proteins was evaluated by immunohistochemistry and western blot analysis. AKF-PD showed no significant effect on renal function in UUO rats. The pathological changes were alleviated significantly after enalapril or AKF-PD treatment, but with no significant differences between the two groups. Col I protein was overexpressed in the UUO group, which was inhibited by both enalapril and AKF-PD. The number of apoptotic renal tubular epithelial cells was much higher in the UUO group, and AKF-PD significantly inhibited epithelial cells apoptosis. The expression of FADD, Apaf-1, and CHOP proteins was significantly upregulated in the UUO group and downregulated by enalapril and AKF-PD. In conclusion, AKF-PD improved renal interstitial fibrosis by inhibiting apoptosis of renal tubular epithelial cells in rats with UUO.


Sujets)
Animaux , Mâle , Pyridones/pharmacologie , Obstruction urétérale/anatomopathologie , Apoptose/effets des médicaments et des substances chimiques , Cellules épithéliales/effets des médicaments et des substances chimiques , Maladies du rein/anatomopathologie , Pyridones/métabolisme , Azote uréique sanguin , Fibrose , Inhibiteurs de l'enzyme de conversion de l'angiotensine/métabolisme , Inhibiteurs de l'enzyme de conversion de l'angiotensine/pharmacologie , Énalapril/métabolisme , Énalapril/pharmacologie , Répartition aléatoire , Rat Sprague-Dawley , Créatinine/sang , Collagène de type I/effets des médicaments et des substances chimiques , Collagène de type I/métabolisme , Modèles animaux de maladie humaine , Facteur de transcription CHOP/effets des médicaments et des substances chimiques , Facteur-1 activateur des protéases apoptotiques/effets des médicaments et des substances chimiques , Facteur-1 activateur des protéases apoptotiques/métabolisme , Protéine à domaine de mort associée à Fas/effets des médicaments et des substances chimiques , Protéine à domaine de mort associée à Fas/métabolisme
4.
Acta cir. bras ; 32(5): 396-406, May 2017. tab, graf
Article Dans Anglais | LILACS | ID: biblio-837708

Résumé

Abstract Purpose: To determine the effects of propofol and ketamine anesthesia on liver regeneration in rats after partial hepatectomy (PHT). Methods: Male Wistar albino rats were assigned randomly to four groups of 10. Anesthesia was induced and maintained with propofol in groups 1 and 2, and with ketamine in groups 3 and 4. PHT was undertaken in groups 1 and 3. Rats in groups 2 and 4 (control groups) underwent an identical surgical procedure, but without PHT. At postoperative day-5, rats were killed. Regenerated liver was removed, weighed, and evaluated (by immunohistochemical means) for expression of inducible nitric oxide synthase (iNOS), endothelial NOS (eNOS), apoptosis protease-activating factor (APAF)-1, and proliferating cell nuclear antigen (PCNA). Also, blood samples were collected for measurement of levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6. Results: Between groups 2 and 4, there were no differences in tissue levels of iNOS, eNOS, and APAF-1 or plasma levels of TNF-α and IL-6. eNOS expression was similar in group 1 and group 3. Expression of iNOS and APAF-1 was mild-to-moderate in group 1, but significantly higher in group 3. Groups 1 and 3 showed an increase in PCNA expression, but expression in both groups was comparable. Plasma levels of TNF-α and IL-6 increased to a lesser degree in group 1 than in group 3. Conclusion: Propofol, as an anesthetic agent, may attenuate cytokine-mediated upregulation of iNOS expression and apoptosis in an animal model of liver regeneration after partial hepatectomy.


Sujets)
Animaux , Mâle , Propofol/pharmacologie , Apoptose , Anesthésiques intraveineux/pharmacologie , Nitric oxide synthase type II/métabolisme , Kétamine/pharmacologie , Régénération hépatique/effets des médicaments et des substances chimiques , Répartition aléatoire , Propofol/métabolisme , Régulation positive , Interleukine-6/métabolisme , Interleukine-6/sang , Rat Wistar , Antigène nucléaire de prolifération cellulaire/métabolisme , Anesthésiques intraveineux/métabolisme , Modèles animaux , Nitric oxide synthase type III/métabolisme , Facteur-1 activateur des protéases apoptotiques/métabolisme , Hépatectomie , Kétamine/métabolisme
5.
Protein & Cell ; (12): 833-843, 2015.
Article Dans Anglais | WPRIM | ID: wpr-757189

Résumé

The protein apoptotic protease activating factor 1 (Apaf1) is the central component of the apoptosome, a multiprotein complex that activates procaspase-9 after cytochrome c release from the mitochondria in the intrinsic pathway of apoptosis. We have developed a vital method that allows fluorescence-activated cell sorting of cells at different stages of the apoptotic pathway and demonstrated that upon pharmacological inhibition of Apaf1, cells recover from doxorubicin- or hypoxia-induced early apoptosis to normal healthy cell. Inhibiting Apaf1 not only prevents procaspase-9 activation but delays massive mitochondrial damage allowing cell recovery.


Sujets)
Humains , Adénosine triphosphate , Métabolisme , Apoptose , Facteur-1 activateur des protéases apoptotiques , Génétique , Métabolisme , Hypoxie cellulaire , Lignée cellulaire tumorale , Doxorubicine , Pharmacologie , Cellules HeLa , Microscopie électronique à transmission
6.
Journal of Experimental Hematology ; (6): 251-254, 2009.
Article Dans Chinois | WPRIM | ID: wpr-302154

Résumé

Apoptotic protease activating factor-1 (Apaf1) is an essential factor in intrinsic mitochondrial pathway of apoptosis activation. Apaf1 leads to the formation of apoptosome, which then proteolytically activates caspase-9. The activated caspase-9 opens the downstream signal of caspases to execute programmed cell death. Apaf-1 is important for tumor suppression and drug resistance because it plays a central role in DNA damage-induced apoptosis. Inactivation of the Apaf-1 gene is implicated in disease progression and chemoresistance of some malignancies. Further research on the Apaf-1 will contribute to develop a new type of approach to anti-cancer drugs, which might have good prospect in clinical practice. In this paper, the structure and function of Apaf-1, the mechanism involved in Apaf-1 signaling pathway, and application of Apaf-1 in tumor therapy were reviewed.


Sujets)
Humains , Apoptose , Facteur-1 activateur des protéases apoptotiques , Métabolisme , Caspase-9 , Métabolisme , Tumeurs , Thérapeutique , Transduction du signal
7.
Braz. j. med. biol. res ; 41(7): 571-578, July 2008. ilus, tab, graf
Article Dans Anglais | LILACS | ID: lil-489516

Résumé

Apoptotic protease activating factor 1 (APAF-1) has a critical role in the regulation of apoptosis. In the present study, the mRNA expression analysis of different APAF-1 transcripts (APAF-1S, APAF-1LC, APAF-1LN, and APAF-1XL) was analyzed in bone marrow samples from 37 patients with acute myeloid leukemia (newly diagnosed, with no previous treatment). APAF-1XL and APAF-1LN transcripts (with and without an extra WD-40 repeat region, respectively) were detected in all samples, although the major form expressed was APAF-1XL in 65 percent of the samples (group 1), while 35 percent of the samples expressed primarily APAF-1LN (group 2). Only 46 percent of the patients presented complete remission in response to remission induction therapy (represented by less than 5 percent marrow blasts and hematological recovery), all but 2 cases being from group 1, 21.6 percent did not attain complete remission (only 1 case from group 1), and 32.4 percent of the patients died early. Lower expression of APAF-1XL (APAF-1XL/APAF-1LN ratio <1.2) was associated with a poor response to therapy (P = 0.0005, Fisher exact test). Both groups showed similar characteristics regarding white blood cell counts, cytogenetic data or presence of gene rearrangements associated with good prognosis as AML1-ETO, CBFB-MYH11 and PML/RARA. Since it has been shown that only the isoforms with the extra WD-40 repeat region activate procaspase-9, we suggest that low procaspase-9 activation may also be involved in the deregulation of apoptosis and chemotherapy resistance in acute myeloid leukemia.


Sujets)
Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Femelle , Humains , Mâle , Adulte d'âge moyen , Jeune adulte , Facteur-1 activateur des protéases apoptotiques/génétique , Leucémie aigüe myéloïde/génétique , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Cellules de la moelle osseuse/composition chimique , Études cas-témoins , Densitométrie , ADN complémentaire/génétique , Régulation de l'expression des gènes tumoraux , Leucémie aigüe myéloïde/traitement médicamenteux , RT-PCR , ARN messager/génétique , Facteurs de transcription , Échec thérapeutique , Transcription génétique/génétique , Marqueurs biologiques tumoraux/génétique , Jeune adulte
8.
J Biosci ; 2007 Mar; 32(2): 261-70
Article Dans Anglais | IMSEAR | ID: sea-110746

Résumé

We report here the isolation of a homologue of the potential anti-apoptotic gene, defender against apoptotic death (dad1 )from Chlamydomonas reinhardtii cells.Using polymerase chain reaction (PCR),we investigated its expression in the execution process of programmed cell death (PCD)in UV-C exposed dying C.reinhardtii cells.Reverse- transcriptase (RT)-PCR showed that C.reinhardtii dad1 amplification was drastically reduced in UV-C exposed dying C.reinhardtii cells.We connect the downregulation of dad1 with the upregulation of apoptosis protease activating factor-1 (APAF-1)and the physiological changes that occur in C.reinhardtii cells upon exposure to 12 J/m 2 UV-C in order to show a reciprocal relationship between proapoptotic and inhibitor of apoptosis factors.The temporal changes indicate a correlation between the onset of cell death and dad1 downregulation.The sequence of the PCR product of the cDNA encoding the dad1 homologue was aligned with the annotated dad1 (C_20215)from the Chlamydomonas database (http://genome.jgi-psf.org:8080/annotator/servlet/jgi.annotation.Annotation?pDb=chlre2); Annotation?pDb=chlre2 );this sequence was found to show 100% identity,both at the nucleotide and amino acid level. The 327 bp transcript showed an open reading frame of 87 amino acid residues.The deduced amino acid sequence of the putative C.reinhardtii DAD1 homologue showed 54% identity with Oryza sativa, 56 identity with Drosophila melanogaster, 66% identity with Xenopus laevis, and 64% identity with Homo sapiens,Sus scrofa,Gallus gallus,Rattus norvegicus and Mus musculus.


Sujets)
Séquence d'acides aminés , Animaux , Apoptose/effets des radiations , Protéines régulatrices de l'apoptose/métabolisme , Facteur-1 activateur des protéases apoptotiques/métabolisme , Séquence nucléotidique , Technique de Western , Chlamydomonas reinhardtii/génétique , Amorces ADN/génétique , Régulation négative/effets des radiations , Données de séquences moléculaires , RT-PCR , Alignement de séquences , Analyse de séquence d'ADN , Rayons ultraviolets
9.
Journal of Veterinary Science ; : 369-378, 2004.
Article Dans Anglais | WPRIM | ID: wpr-79776

Résumé

Evidences show that eukaryotic mRNAs can perform protein translation through internal ribosome entry sites (IRES). 5'-Untranslated region of the mRNA encoding apoptotic protease-activating factor 1 (Apaf-1) contains IRES, and, thus, can be translated in a cap-independent manner. Effects of changes in protein translation pattern through rapamycin pretreatment on 4-(methylnitrosamino)-1-(3-pyridyl)-butanone(NNK, tobacco-specific lung carcinogen)-induced apoptosis in human bronchial epithelial cells were examined by caspase assay, FACS analysis, Western blotting, and transient transfection. Results showed that NNK induced apoptosis in concentration- and time-dependent manners. NNK-induced apoptosis occurred initially through cap-independent protein translation, which during later stage was replaced by cap-dependent protein translation. Our data may be pplicable as the mechanical basis of lung cancer treatment.


Sujets)
Humains , Antibiotiques antinéoplasiques/pharmacologie , Apoptose/effets des médicaments et des substances chimiques , Facteur-1 activateur des protéases apoptotiques , Protéine Bid , Technique de Western , Bronches/métabolisme , Cancérogènes/pharmacologie , Protéines de transport/métabolisme , Caspases/métabolisme , Cytochromes c/métabolisme , Relation dose-effet des médicaments , Cellules épithéliales/métabolisme , Facteur-4E d'initiation eucaryote/métabolisme , Cytométrie en flux , Nitrosamines/pharmacologie , Biosynthèse des protéines , Protéines/métabolisme , Protéines proto-oncogènes c-bcl-2/métabolisme , Protéines de liaison à la coiffe de l'ARN/physiologie , Sirolimus/pharmacologie , Facteurs temps , Protéine Bax
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