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1.
Eur J Neurosci ; 58(3): 2807-2823, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37452644

RESUMEN

The bed nucleus of the stria terminalis (BNST) is a neuropeptide-enriched brain region that modulates a wide variety of emotional behaviours and states, including stress, anxiety, reward and social interaction. The BNST consists of diverse subregions and neuronal ensembles; however, because of the high molecular heterogeneity within BNST neurons, the mechanisms through which the BNST regulates distinct emotional behaviours remain largely unclear. Prior studies have identified BNST calretinin (CR)-expressing neurons, which lack neuropeptides. Here, employing virus-based cell-type-specific retrograde and anterograde tracing systems, we mapped the whole-brain monosynaptic inputs and axonal projections of BNST CR-expressing neurons in male mice. We found that BNST CR-expressing neurons received inputs mainly from the amygdalopiriform transition area, central amygdala and hippocampus and moderately from the medial preoptic area, basolateral amygdala, paraventricular thalamus and lateral hypothalamus. Within the BNST, plenty of input neurons were primarily located in the oval and interfascicular subregions. Furthermore, numerous BNST CR-expressing neuronal boutons were observed within the BNST but not in other brain regions, thus suggesting that these neurons are a type of interneuron. These results will help further elucidate the neuronal circuits underlying the elaborate and distinct functions of the BNST.


Asunto(s)
Neuropéptidos , Núcleos Septales , Ratones , Masculino , Animales , Núcleos Septales/metabolismo , Calbindina 2 , Encéfalo/metabolismo , Neuropéptidos/metabolismo , Interneuronas/metabolismo
2.
Biochem Biophys Res Commun ; 468(4): 617-21, 2015 Dec 25.
Artículo en Inglés | MEDLINE | ID: mdl-26546817

RESUMEN

Previous studies have shown that Apelin-13 upregulates early growth response factor-1 (Egr-1) via the extracellular signal-regulated protein kinase (ERK) signaling pathway. Apelin-13 induces proliferation and migration of vascular smooth muscle cells (VSMCs) as well as the upregulation of osteopontin (OPN) via the upregulation of Egr-1. This study was designed to further explore the activity of Apelin-13 in VSMCs by investigating members of the mitogen-activated protein kinase (MAPK) family, in particular Jun kinase (JNK) and p38 mitogen-activated protein kinase (P38). We also examined whether the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) and protein kinase C (PKC) signaling pathways were involved in the regulation of Egr-1 by Apelin-13. We treated rat aortic VSMCs with Apelin-13 and examined the expression of JNK, p-JNK, P38, and p-P38 to investigate whether Apelin-13-mediated increases in Egr-1 occurred through the JNK and P38 signaling pathways. We then pretreated VSMCs with the Gi protein inhibitor pertussis toxin (PTX) and the Gq inhibitor YM254890, added Apelin-13 and looked for changes in Egr-1 expression. Finally, we pretreated with the PI3K inhibitor LY294002 and the PKC inhibitor GF109203X, and treated with Apelin-13. Our results showed that JNK and P38 did not participate in Apelin-13-mediated increase in Egr-1. Instead, Apelin-13 upregulation of Egr-1 was mediated by a PTX-sensitive Gi protein. Apelin-13 did increase ERK phosphorylation through the PI3K/Akt and PKC signaling pathways, resulting in changes in Egr-1 expression. These data provide important targets for future studies to modulate vascular remodeling.


Asunto(s)
Proteína 1 de la Respuesta de Crecimiento Precoz/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Músculo Liso Vascular/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteína Quinasa C/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Animales , Células Cultivadas , Músculo Liso Vascular/citología , Miocitos del Músculo Liso/citología , Miocitos del Músculo Liso/metabolismo , Ratas , Transducción de Señal/fisiología , Regulación hacia Arriba/fisiología
3.
CNS Neurosci Ther ; 30(2): e14637, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38380702

RESUMEN

AIMS: Sleep disorders are prevalent among stroke survivors and impede stroke recovery, yet they are still insufficiently considered in the management of stroke patients, and the mechanisms by which they occur remain unclear. There is evidence that boosting phasic GABA signaling with zolpidem during the repair phase improves stroke recovery by enhancing neural plasticity; however, as a non-benzodiazepine hypnotic, the effects of zolpidem on post-stroke sleep disorders remain unclear. METHOD: Transient ischemic stroke in male rats was induced with a 30-minute middle cerebral artery occlusion. Zolpidem or vehicle was intraperitoneally delivered once daily from 2 to 7 days after the stroke, and the electroencephalogram and electromyogram were recorded simultaneously. At 24 h after ischemia, c-Fos immunostaining was used to assess the effect of transient ischemic stroke and acute zolpidem treatment on neuronal activity. RESULTS: In addition to the effects on reducing brain damage and mitigating behavioral deficits, repeated zolpidem treatment during the subacute phase of stroke quickly ameliorated circadian rhythm disruption, alleviated sleep fragmentation, and increased sleep depth in ischemic rats. Immunohistochemical staining showed that in contrast to robust activation in para-infarct and some remote areas by 24 h after the onset of focal ischemia, the activity of the ipsilateral suprachiasmatic nucleus, the biological rhythm center, was strongly suppressed. A single dose of zolpidem significantly upregulated c-Fos expression in the ipsilateral suprachiasmatic nucleus to levels comparable to the contralateral side. CONCLUSION: Stroke leads to suprachiasmatic nucleus dysfunction. Zolpidem restores suprachiasmatic nucleus activity and effectively alleviates post-stroke sleep disturbances, indicating its potential to promote stroke recovery.


Asunto(s)
Accidente Cerebrovascular Isquémico , Trastornos del Sueño-Vigilia , Accidente Cerebrovascular , Humanos , Masculino , Ratas , Animales , Zolpidem/farmacología , Zolpidem/uso terapéutico , Piridinas/farmacología , Piridinas/uso terapéutico , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/tratamiento farmacológico , Trastornos del Sueño-Vigilia/tratamiento farmacológico , Trastornos del Sueño-Vigilia/etiología , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Sueño , Accidente Cerebrovascular Isquémico/tratamiento farmacológico
4.
Biochem Biophys Res Commun ; 439(2): 235-40, 2013 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-23973488

RESUMEN

Apelin-13 plays an important role in the migration and proliferation of vascular smooth muscle cells (VSMCs); however, the underlying mechanisms are still unclear. Egr-1 is a nuclear transcription factor, which is considered to be the critical initiating factor of the processes of VSMC proliferation and migration. Egr-1 is known to regulate the expression of osteopontin (OPN), which is a marker of the phenotypic modulation that is a necessary condition of VSMC proliferation and migration. We hypothesized that the role of Apelin-13 is mediated via upregulation of Egr-1. To test this hypothesis, we analyzed the effects of Apelin-13 treatment on Egr-1 mRNA and protein expression in A10 rat aortic VSMCs by RT-PCR and Western blotting, respectively. Results showed that, Apelin-13 upregulated the expression of Egr-1. Furthermore, treatment with the extracellular-regulated protein kinase (ERK) inhibitor, PD98059, inhibited the upregulation of Egr-1 by Apelin-13. In addition, this upregulation was inhibited by treatment of VSMCs with the Egr-1 specific deoxyribozyme ED5 (DNAenzyme/10-23 DRz). Furthermore, ED5 treatment was found to significantly inhibit Apelin-13-induced migration and proliferation of VSMCs using transwell and MTT assays, respectively. The evaluation of OPN mRNA and protein expression levels by RT-PCR and Western blot analyses revealed that ED5 treatment also inhibited Apelin-13-induced OPN upregulation. The results of this study indicated that Apelin-13 upregulates Egr-1 via ERK. Furthermore, Apelin-13 induced the proliferation and migration of VSMCs as well as the upregulation of OPN via the upregulation of Egr-1. These results will provide an important theoretical and experimental basis for the control of inappropriate remodeling of vessel walls, and will hopefully lead to the prevention and treatment of vascular remodeling diseases.


Asunto(s)
Proteína 1 de la Respuesta de Crecimiento Precoz/genética , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Miocitos del Músculo Liso/citología , Miocitos del Músculo Liso/metabolismo , Regulación hacia Arriba , Animales , Línea Celular , Movimiento Celular , Proliferación Celular , Proteína 1 de la Respuesta de Crecimiento Precoz/metabolismo , Sistema de Señalización de MAP Quinasas , Osteopontina/genética , Ratas
5.
Zhonghua Yi Xue Za Zhi ; 93(30): 2388-91, 2013 Aug 13.
Artículo en Zh | MEDLINE | ID: mdl-24300209

RESUMEN

OBJECTIVE: To evaluate the efficacy and safety of submucosal tunneling endoscopic resection (STER) in the treatment of middle and lower esophagus submucosal tumors (SMT) originating from muscularis propria (MP) layer. METHODS: A total number of 33 esophagus submucosal tumor (SMT) originating from MP layer underwent tumor resection by STER after endoscopic ultrasonography (EUS) and CT examination at Endoscopy Center, Department of Gastroenterology, First Affiliated Hospital, Nanjing Medical University from March 2012 to March 2013. There were 17 males and 16 females with an age range of (50 ± 10) years. Their lesion size, lesion origin, pathology, operative duration and complication rate were analyzed. RESULTS: Among them, the origins were of submucosal (n = 4, 12.1%), superficial muscularis propria layer (SMP) (n = 18, 54.6%), deep muscularis layer (DMP) (n = 10, 30.3%) and serosa (n = 1, 3.0%). There were single tumor (n = 30, 90.9%), double tumors (n = 2, 6.1%) and triple tumors (n = 1, 3.0%). Except for 1 case of non-resected hemangioma, 36 operative specimens were examined pathologically, including 30 leiomyomas tumors (83.3%), 5 stromal tumors (GIST) (13.9%) and 1 lipoma tumor (2.8%). Thirty-two lesions were successfully resected by STER with a complete resection rate of 97.0%. Average lesion size was (1.7 ± 1.0) cm and average operative duration (49 ± 26) min. A number of (7.8 ± 2.5) hemostatic clips were used to close the mucosal incision site. Subcutaneous emphysema occurred in 3 patients (9.1%) while puncture and pneumothorax developed in one case (3.0%). All of them recovered uneventfully through conservative treatments. CONCLUSIONS: As a new safe, efficacious and feasible treatment for middle and lower esophagus submucosal tumors, STER may completely resect SMT and provide accurate histopathological evaluations. And it is feasible to regain the mucosal integrity of GI tract and prevent the occurrences of leakage and secondary infections.


Asunto(s)
Endoscopía del Sistema Digestivo/métodos , Neoplasias Esofágicas/cirugía , Membrana Mucosa/cirugía , Adulto , Anciano , Neoplasias Esofágicas/patología , Esófago/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Membrana Mucosa/patología , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
6.
Commun Biol ; 6(1): 372, 2023 04 05.
Artículo en Inglés | MEDLINE | ID: mdl-37020138

RESUMEN

Cuttage propagation involves adventitious root formation induced by auxin. In our previous study, Larix kaempferi BABY BOOM 1 (LkBBM1), which is known to regulate adventitious root formation, was affected by auxin. However, the relationship between LkBBM1 and auxin remains unclear. Auxin response factors (ARFs) are a class of important transcription factors in the auxin signaling pathway and modulate the expression of early auxin-responsive genes by binding to auxin response elements. In the present study, we identified 14 L. kaempferi ARFs (LkARFs), and found LkARF7 and LkARF19 bound to LkBBM1 promoter and enhanced its transcription using yeast one-hybrid, ChIP-qPCR, and dual-luciferase assays. In addition, the treatment with naphthalene acetic acid promoted the expression of LkARF7 and LkARF19. We also found that overexpression of these two genes in poplar promoted adventitious root formation. Furthermore, LkARF19 interacted with the DEAD-box ATP-dependent RNA helicase 53-like protein to form a heterodimer to regulate adventitious root formation. Altogether, our results reveal an additional regulatory mechanism underlying the control of adventitious root formation by auxin.


Asunto(s)
Larix , Larix/genética , Larix/metabolismo , Raíces de Plantas/metabolismo , Crecimiento Demográfico , Ácidos Indolacéticos/metabolismo , Regiones Promotoras Genéticas
7.
Nat Commun ; 14(1): 610, 2023 02 04.
Artículo en Inglés | MEDLINE | ID: mdl-36739462

RESUMEN

It is critical to understand factors associated with nasopharyngeal carcinoma (NPC) metastasis. To track the evolutionary route of metastasis, here we perform an integrative genomic analysis of 163 matched blood and primary, regional lymph node metastasis and distant metastasis tumour samples, combined with single-cell RNA-seq on 11 samples from two patients. The mutation burden, gene mutation frequency, mutation signature, and copy number frequency are similar between metastatic tumours and primary and regional lymph node tumours. There are two distinct evolutionary routes of metastasis, including metastases evolved from regional lymph nodes (lymphatic route, 61.5%, 8/13) and from primary tumours (hematogenous route, 38.5%, 5/13). The hematogenous route is characterised by higher IFN-γ response gene expression and a higher fraction of exhausted CD8+ T cells. Based on a radiomics model, we find that the hematogenous group has significantly better progression-free survival and PD-1 immunotherapy response, while the lymphatic group has a better response to locoregional radiotherapy.


Asunto(s)
Carcinoma , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/patología , Relevancia Clínica , Linfocitos T CD8-positivos/patología , Metástasis Linfática/patología , Carcinoma/genética , Carcinoma/patología , Ganglios Linfáticos/patología
8.
Sci Rep ; 12(1): 258, 2022 01 07.
Artículo en Inglés | MEDLINE | ID: mdl-34997161

RESUMEN

The radial change (RC) of tree stem is the process of heartwood formation involved in complex molecular mechanism. Chinese fir (Cunninghamia lanceolata (Lamb.) Hook.), an evergreen species, is an important fast-growing timber tree in southern China. In this study, the top four stable genes (IDH, UBC2, RCA and H2B) were selected in RC tissues of 15 years old Chinese fir stem (RC15) and the genes (H2B, 18S, TIP41 and GAPDH) were selected in RC tissues of 30 years old Chinese fir stem (RC30). The stability of the reference genes is higher in RC30 than in RC15. Sixty-one MYB transcripts were obtained on the PacBio Sequel platform from woody tissues of one 30 years old Chinese fir stem. Based on the number of MYB DNA-binding domain and phylogenetic relationships, the ClMYB transcripts contained 21 transcripts of MYB-related proteins (1R-MYB), 39 transcripts of R2R3-MYB proteins (2R-MYB), one transcript of R1R2R3-MYB protein (3R-MYB) belonged to 18 function-annotated clades and two function-unknown clades. In RC woody tissues of 30 years old Chinese fir stem, ClMYB22 was the transcript with the greatest fold change detected by both RNA-seq and qRT-PCR. Reference genes selected in this study will be helpful for further verification of transcript abundance patterns during the heartwood formation of Chinese fir.


Asunto(s)
Cunninghamia/genética , Genes de Plantas , Genes myb , Proteínas Proto-Oncogénicas c-myb/genética , Transcriptoma , Xilema/genética , Cunninghamia/crecimiento & desarrollo , Cunninghamia/metabolismo , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Filogenia , Proteínas Proto-Oncogénicas c-myb/metabolismo , RNA-Seq , Xilema/crecimiento & desarrollo , Xilema/metabolismo
9.
Ying Yong Sheng Tai Xue Bao ; 31(8): 2804-2816, 2020 Aug.
Artículo en Zh | MEDLINE | ID: mdl-34494804

RESUMEN

The regulative function of green quantity in urban thermal environment is an important topic in urban studies. Here, we reviewed the concepts and developments of green quantity, the measurements of green quantity and urban thermal environment, the relevance between green quantity and urban thermal environment, and its implications for urban planning. After summarizing domestic and international research processes, we put forward four prospective directions: 1) improving the methods for three-dimensional investigation of green quantity, 2) developing means for urban thermal environment monitoring and forecasting, 3) establishing an index system for three-dimensional pattern of urban green quantity, and 4) creating three-dimensional analytical methods to quantify the relationship between green quantity and urban thermal environment. It was expected to provide a three-dimensional spatial perspective for exploring the relevance between green quantity and urban thermal environment. It was proposed to deeply examine three-dimensional patterns of urban green quantity, in order to balance urban thermal environment and multiple ecological benefits, and to provide scientific basis for urban green space planning and design, as well as to form theoretical supports for adaptation to climate change and regulation of urban thermal environments.


Asunto(s)
Planificación de Ciudades , Parques Recreativos , Aclimatación , Ciudades , Cambio Climático , Estudios Prospectivos
10.
Tree Physiol ; 40(11): 1487-1508, 2020 10 29.
Artículo en Inglés | MEDLINE | ID: mdl-32705116

RESUMEN

Moso bamboo (Phyllostachys edulis (Carriere) J. Houzeau) is a rapidly growing grass of industrial and ecological importance. However, the molecular mechanisms of its remarkable growth are not well understood. In this study, we investigated the early-stage growth of moso bamboo shoots and defined three different growth stages based on histological and biochemical analyses, namely, starting of cell division (SD), rapid division (RD) and rapid elongation (RE). Further analyses on potentially relevant cellular pathways in these growth stages using multi-omics approaches such as transcriptomics and proteomics revealed the involvement of multiple cellular pathways, including DNA replication, repair and ribosome biogenesis. A total of 8045 differentially expressed genes (DEGs) and 1053 differentially expressed proteins (DEPs) were identified in our analyses. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of detected DEGs identified several key biological pathways such as phytohormone metabolism, signal transduction, cell wall development and carbohydrate metabolism. The comparative analysis of proteins displayed that a total of 213 DEPs corresponded with DEGs and 3 significant expression profiles that could be promoting the fast growth of bamboo internodes. Moreover, protein-protein interaction network prediction analysis is suggestive of the involvement of five major proteins of signal transduction, DNA synthesis and RNA transcription, and may act as key elements responsible for the rapid shoot growth. Our work exploits multi-omics and bioinformatic approaches to unfurl the complexity of molecular networks involved in the rapid growth of moso bamboo and opens up questions related to the interactions between the functions played by individual molecular pathway.


Asunto(s)
Regulación de la Expresión Génica de las Plantas , Poaceae , Pared Celular , Reguladores del Crecimiento de las Plantas
11.
World J Gastroenterol ; 22(48): 10625-10630, 2016 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-28082815

RESUMEN

AIM: To evaluate diagnostic yields of capsule endoscopy (CE) and/or single-balloon enteroscopy (SBE) in patients with suspected small bowel diseases. METHODS: We retrospectively analyzed 700 patients with suspected small bowel diseases from September 2010 to March 2016. CE, SBE, or SBE with prior CE was performed in 401, 353, and 47 patients, respectively. Data from clinical and endoscopy records were collected for analysis. Indications, procedure times, diagnostic yields, and complications were summarized and evaluated. RESULTS: The overall diagnostic yield for the CE group was 57.6%. The diagnostic yield of CE in patients with obscure gastrointestinal bleeding (OGIB) was significantly greater than that in patients with no bleeding (70.5% vs 43.8%, P < 0.01). The overall diagnostic yield of SBE was 69.7%. There was no difference in the diagnostic yield of SBE between patients with OGIB and those with no bleeding (72.5% vs 68.9%, P = 0.534). Forty-seven patients underwent CE prior to SBE. Among them, the diagnostic yield of SBE with positive findings on prior CE was 93.3%. In addition, SBE detected two cases with superficial ulcer and erosive lesions in the small bowel, which were missed by CE. However, one case with lymphoma and two with Crohn's disease were not confirmed by SBE. The rate of capsule retention was 2.0%. There were no significant complications during or after SBE examinations. CONCLUSION: SBE is a safe and effective technique for diagnosing small bowel diseases. SBE with prior CE seemed to improve the diagnostic yield of small bowel diseases.


Asunto(s)
Endoscopía Capsular , Hemorragia Gastrointestinal/diagnóstico , Enfermedades Intestinales/diagnóstico , Enteroscopia de Balón Individual , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad de Crohn/diagnóstico , Úlcera Duodenal/diagnóstico , Femenino , Humanos , Neoplasias Intestinales/diagnóstico , Intestino Delgado/patología , Linfoma/diagnóstico , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto Joven
12.
Chin Med J (Engl) ; 128(6): 784-9, 2015 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-25758273

RESUMEN

BACKGROUND: Current randomized trials have demonstrated the effects of short-term rosuvastatin therapy in preventing contrast-induced acute kidney injury (CIAKI). However, the consistency of these effects on patients administered different volumes of contrast media is unknown. METHODS: In the TRACK-D trial, 2998 patients with type 2 diabetes and concomitant chronic kidney disease (CKD) who underwent coronary/peripheral arterial angiography with or without percutaneous intervention were randomized to short-term (2 days before and 3 days after procedure) rosuvastatin therapy or standard-of-care. This prespecified analysis compared the effects of rosuvastatin versus standard therapy in patients exposed to (moderate contrast volume [MCV], 200-300 ml, n = 712) or (high contrast volume [HCV], ≥ 300 ml, n = 220). The primary outcome was the incidence of CIAKI. The secondary outcome was a composite of death, dialysis/hemofiltration or worsened heart failure at 30 days. RESULTS: Rosuvastatin treatment was associated with a significant reduction in CIAKI compared with the controls (2.1% vs. 4.4%, P = 0.050) in the overall cohort and in patients with MCV (1.7% vs. 4.5%, P = 0.029), whereas no benefit was observed in patients with HCV (3.4% vs. 3.9%, P = 0.834). The incidence of secondary outcomes was significantly lower in the rosuvastatin group compared with control group (2.7% vs. 5.3%, P = 0.049) in the overall cohort, but it was similar between the patients with MCV (2.0% vs. 4.2%, P = 0.081) or HCV (5.1% vs. 8.8%, P = 0.273). CONCLUSIONS: Periprocedural short-term rosuvastatin treatment is effective in reducing CIAKI and adverse clinical events for patients with diabetes and CKD after their exposure to a moderate volume of contrast medium.


Asunto(s)
Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/prevención & control , Medios de Contraste/efectos adversos , Fluorobencenos/uso terapéutico , Pirimidinas/uso terapéutico , Sulfonamidas/uso terapéutico , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Rosuvastatina Cálcica , Resultado del Tratamiento
13.
Chem Biol Interact ; 147(2): 119-27, 2004 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-15013814

RESUMEN

A natural polypeptide from marine Chlamys farreri (a kind of scallop) (PCF), has been recently been found to be an effective photoprotective agent against ultraviolet rays B (UVB)-induced mitochondria damage in normal human fibroblasts. To investigate whether PCF has the antiapoptotic effect on human keratinocytes, in the present study, we established an apoptotic model on HaCaT cell line by means of UVB radiance of 30 mJ/cm(2) and compared the effect of different PCF treatments on UVB-radiated cells. Flow cytometry analyses showed that PCF treatment before UVB-irradiation inhibited UVB-induced apoptosis, the loss of mitochondrial membrane potential (Deltapsim) and the increase of free Ca(2+) level in HaCaT cells. In parallel with these results, UVB-irradiation enhanced activities of caspases-3, 8, 9, while this enhancement was inhibited by PCF treatment prior to irradiation. PCF added after irradiation neither reduced UVB-induced activities of the three caspases nor synergized the effect of pre-added PCF. Cellular ultrastructural features obtained from transmission electron microscopy further confirmed the antiapoptotic effect of PCF pre-treatment. It is concluded that the antiapoptotic effect of PCF is not therapeutic but prophylactic. Caspases-3, 8, 9, Deltapsim and calcium are involved in UVB-induced apoptosis, while prophylactic PCF inhibits apoptosis of UVB-irradiated HaCaT cells by blocking the caspases activities, the Deltapsim lost and the elevation of intracellular free Ca(2+) level.


Asunto(s)
Apoptosis/efectos de los fármacos , Queratinocitos/efectos de los fármacos , Moluscos/química , Péptidos/farmacología , Protectores Solares/farmacología , Animales , Apoptosis/efectos de la radiación , Calcio/metabolismo , Caspasas/biosíntesis , Línea Celular Transformada , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Citometría de Flujo , Humanos , Queratinocitos/efectos de la radiación , Queratinocitos/ultraestructura , Potenciales de la Membrana/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/fisiología , Mitocondrias/efectos de la radiación , Péptidos/aislamiento & purificación , Protectores Solares/aislamiento & purificación , Rayos Ultravioleta
14.
J Geriatr Cardiol ; 10(1): 52-8, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23610574

RESUMEN

OBJECTIVE: To investigate the effects of tirofiban on the no-reflow phenomenon of acute myocardial infarction (AMI) rats received reperfusion, as well as the underlying mechanisms. METHODS: Fifty-six male Sprague-Dawley rats were randomly divided into four groups: Sham operation group (Sham), AMI/reperfusion group (AMI/R), Tirofiban group (Tiro) and Tiro+N-nitro-L-arginine group (L-NNA; an endothelial nitric oxide synthase inhibitor). To generate the animal model mimicking the no-reflow phenomenon, the rats first received occlusion of the left anterior descending coronary artery for 60 min and then followed by reperfusion for 120 min. Area of no-reflow, area at risk and area of necrosis were measured by thioflavine S, Evans blue and triphenyl tetrazolium chloride staining, respectively. Haemodynamic function was measured at the end. In the meantime, nitric oxide synthase (NOS) activity was determined by a NOS assay kit. The expression of myocardial endothelial nitric oxide synthase (eNOS) was determined by an enzyme-linked immunosorbent assay (ELISA). The expression of phosphorylated eNOS at Ser(1177) (p-eNOS Ser(1177)) and vascular endothelial-cadherin (VE-cadherin) were determined by western blot. RESULTS: Compared with AMI/R group, tirofiban significantly reduced the no-reflow area and infarct size (all P < 0.05). Tirofiban elevated eNOS activity, lessen inducible nitric oxide synthase (iNOS) activity and increased the expression of Ser(1177) phosphorylated eNOS and VE-cadherin in the ischemic myocardium (all P < 0.05). No statistical differences were found in the expression of eNOS among the four groups. Also, tirofiban improved cardiac function with significantly higher levels of left ventricular end systolic pressure, maximum change rate of left ventricular pressure rise and fall, heart rate, and lower level of left ventricular end diastolic pressure than those of the AMI/R group (all P < 0.05). Whereas, these effects of tirofiban were partially abolished by L-NNA. CONCLUSIONS: Tirofiban could reduce the size of no-reflow and infarct. A possible mechanism underlying this effect is that tirofiban could protect the structural and functional integrity of microvascular endothelium which is partially regulated by eNOS activity.

15.
Chin Med J (Engl) ; 122(19): 2360-5, 2009 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-20079140

RESUMEN

BACKGROUND: Apoptosis is a major cause of ischemic heart dysfunction. Apelin, the endogenous ligand for the G-protein-coupled APJ receptor, has been reported to exert cardioprotective effects during myocardial injury. The aim of this study was to investigate the effects of apelin on apoptosis of rat cardiomyocytes induced by glucose deprivation (GD) and study the related signaling pathway. METHODS: Apelin and APJ mRNA expression were determined by RT-PCR in neonatal rat cardiomyocytes during different durations of GD. Cardiomyocyte apoptosis was detected by annexin V-FITC/propidium iodide (PI) staining after GD for 12 hours with or without apelin-13 (10 and 100 nmol/L) pretreatment. Protein levels of Akt and the mammalian target of rapamycin (mTOR) as well as cell apoptosis were detected in the presence or absence of LY294002 (a phosphatidylinositol 3-kinases (PI3K) inhibitor) or rapamycin (a mTOR inhibitor). RESULTS: Apelin mRNA expression was up-regulated when cardiomyocytes were exposed to GD for 6, 12, 18, and 24 hours compared with the base level (P > 0.05, P < 0.01, P < 0.01, P < 0.01). However, when cardiomyocytes were exposed to GD for up to 36 hours, apelin mRNA expression was 17% lower than the base level (P < 0.05). APJ mRNA expression paralleled that of apelin. Apelin-13 pretreatment at 100 nmol/L significantly inhibited GD-induced cardiomyocyte apoptosis (P < 0.05) and increased Akt and mTOR phosphorylation (P < 0.01, P < 0.01). At the same time apelin-13 (100 nmol/L) up-regulated Bcl-2 protein expression and down-regulated Bax and cleaved caspase-3 expression (P < 0.01, P < 0.05, P < 0.05). The anti-apoptotic effect of apelin-13 was blocked by LY294002 (P < 0.01) but not by rapamycin. CONCLUSIONS: The endogenous apelin-APJ system is compensatorily up-regulated and ultimately down-regulated following sustained myocardial ischemia. Apelin protects against ischemic cardiomyocyte apoptosis via activation of the PI3K/Akt pathway.


Asunto(s)
Apoptosis , Proteínas Portadoras/fisiología , Glucosa/deficiencia , Miocitos Cardíacos/fisiología , Animales , Apelina , Receptores de Apelina , Proteínas Portadoras/genética , Caspasa 3/análisis , Supervivencia Celular , Células Cultivadas , Péptidos y Proteínas de Señalización Intercelular , Fosfatidilinositol 3-Quinasas/fisiología , Proteínas Proto-Oncogénicas c-akt/fisiología , Proteínas Proto-Oncogénicas c-bcl-2/análisis , ARN Mensajero/análisis , Ratas , Ratas Sprague-Dawley , Receptores Acoplados a Proteínas G/fisiología , Transducción de Señal , Proteína X Asociada a bcl-2/análisis
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