VEGF inhibition alters neurotrophin signalling pathways and induces caspase‐3 activation and autophagy in rabbit retina

2019 ◽  
Vol 234 (10) ◽  
pp. 18297-18307 ◽  
Author(s):  
Marco Segatto ◽  
Elena Fico ◽  
Magda Gharbiya ◽  
Pamela Rosso ◽  
Valentina Carito ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Signalling Pathways ◽  
Rabbit Retina ◽  
Vegf Inhibition

scholarly journals The Effect of Intravitreal Azithromycin on the Albino Newborn Rabbit Retina

2016 ◽  
Vol 10 (1) ◽  
pp. 12-16
Author(s):  
Duygu Cam ◽  
Ali Osman Saatci ◽  
Serap Cilaker Micili ◽  
Bekir Ugur Ergur ◽  
Revan Yildirim Karabag ◽  
...  
Keyword(s):  
Light Microscopy ◽  
Caspase 3 ◽  
Rabbit Model ◽  
Study Groups ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Control Group ◽  
Tunel Staining ◽  
Rabbit Retina ◽  
Newborn Rabbit ◽  
The Right

Purpose: To evaluate the effect of intravitreal azithromycin on the retina in a newborn rabbit model. Methods: Twelve, two-week old New Zealand albino rabbits were divided into two groups (six in each). The right eyes of six rabbits received 0.75 mg (0.05 mL) azithromycin and the right eyes of the remaining six rabbits 1.5 mg (0.1 mL) azithromycin intravitreally. Left eyes were served as the control and received the same volume of saline. All eyes were enucleated at the third postinjection week. Retinal histology was examined by light microscopy. Apoptosis of the retinal cells was further evaluated by immunohistochemical staining for caspase-3 and in situ terminal deoxynucleotidyl transferase-mediated biotin-deoxyuridine triphosphate nick-end labeling (TUNEL) of DNA fragments. Results: Light microscopy demonstrated no retinal abnormalities in all eyes. However, retinal nuclear DNA fragmentation was evident in both study groups (33.6% with 1.5 mg and 21.4% with 0.75 mg azithromycin) with the TUNEL method. TUNEL staining ratio was statistically higher only in the second group treated with 1.5 mg azithromycin when compared to the control group (p=0.01 Mann Whitney U test). The ratio of caspase-3 positive cells in the two study groups was 21.5% and 20.2%, respectively. Caspase-3 staining ratio was statistically higher in both study groups when compared to the control eyes (p=0.00, p=0.00 respectively). The difference of TUNEL staining ratio between the two study groups was statistically significant (p=0.028), but there were no statistically significant differences in the two study groups by caspase-3 staining (p=0.247). Conclusion: In newborn rabbits, intravitreal azithromycin injection resulted in an apoptotic activity in the photoreceptor, bipolar and ganglion cells. Immunohistochemical analysis suggested that doses of 0.75 mg and 1.5 mg azithromycin, administered intravitreally might be toxic to the newborn rabbit retina.

scholarly journals Baicalein inhibits neuroapoptosis via pathways in sevoflurane induced rats

2018 ◽  
Vol 9 (1) ◽  
pp. 88-98 ◽  
Author(s):  
Si Wang ◽  
Yu Zhou
Keyword(s):  
Neuronal Apoptosis ◽  
Caspase 3 ◽  
Cognitive Impairments ◽  
Survivin Expression ◽  
Signalling Pathways ◽  
Akt Pathway ◽  
Memory Retention ◽  
Neonatal Rats ◽  
Improved Learning ◽  
Gsk 3Β

Abstract Background Baicalein, a bioactive flavonoid was explored for its capability to attenuate sevoflurane induced neuronal apoptosis and to improve behavioural and cognitive impairments. Sevoflurane is a frequently used inhalation anesthetic in neonates and children. Neonatal sevoflurane exposure causes widespread neurodegeneration and cognitive impairments. Development of compounds that could effectively prevent/reduce the adverse effects is of tremendous medical value. Methods Isolated groups of neonatal rats were regulated with baicalein (25, 50 or 100 mg/kg b.wt) from postnatal day 3 (P3) to P21 and were exposed to sevoflurane (3%; 6 h) on P7. Results: Baicalein inhibited sevoflurane induced neuroapoptosis significantly as assessed by TUNEL assay. The raised levels of cleaved caspase-3, Bad and Bax were down-regulated by baicalein with enhanced Bcl-2, Bcl-xL, xIAP, c-IAP-1, c-IAP-2 and survivin expression. Baicalein regulated JNK/ERK signalling and also activated the PI3K/Akt pathway effectively as evident from the increased Akt, phospho-Akt, GSK-3β, phospho-GSK-3β levels. Baicalein, also improved the behaviour of animals in open filed and olfactory tests. The freezing responses and the performance in Morris Water Maze tests were enhanced. Conclusion Baicalein reduced neurodegeneration and improved learning and memory retention of rats and as well modulated PI3/Akt/GSK-3β and JNK/ERK signalling pathways.

Early inhaled nitric oxide treatment decreases apoptosis of endothelial cells in neonatal rat lungs after vascular endothelial growth factor inhibition

2007 ◽  
Vol 293 (5) ◽  
pp. L1271-L1280 ◽  
Author(s):  
Jen-Ruey Tang ◽  
Gregory Seedorf ◽  
Vivek Balasubramaniam ◽  
Anne Maxey ◽  
Neil Markham ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Caspase 3 ◽  
Neonatal Rat ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Lung Growth ◽  
Vegf Inhibition ◽  
Endothelial Growth Factor ◽  
Active Caspase

Vascular endothelial growth factor (VEGF) receptor blockade impairs lung growth and decreases nitric oxide (NO) production in neonatal rat lungs. Inhaled NO (iNO) treatment after VEGF inhibition preserves lung growth in infant rats by unknown mechanisms. We hypothesized that neonatal VEGF inhibition disrupts lung growth by causing apoptosis in endothelial cells, which is attenuated by early iNO treatment. Three-day-old rats received SU-5416, an inhibitor of VEGF receptor, or its vehicle and were raised in room air with or without iNO (10 ppm). SU-5416 reduced alveolar counts and lung vessel density by 28% ( P < 0.005) and 21% ( P < 0.05), respectively, as early as at 7 days of age. SU-5416 increased lung active caspase-3 protein by 60% at 5 days of age ( P < 0.05), which subsided by 7 days of age, suggesting a transient increase in lung apoptosis after VEGF blockade. Apoptosis primarily colocalized to lung vascular endothelial cells, and SU-5416 increased endothelial cell apoptotic index by eightfold at 5 days of age ( P <0.0001). iNO treatment after SU-5416 prevented the increases in lung active caspase-3 and in endothelial cell apoptotic index. There was no difference in alveolar type 2 cell number between control and SU-5416-treated rats. We conclude that neonatal VEGF receptor inhibition causes transient apoptosis in pulmonary endothelium, which is followed by persistently impaired lung growth. Early iNO treatment after VEGF inhibition reduces endothelial cell apoptosis in neonatal lungs. We speculate that enhancing endothelial cell survival after lung injury may preserve neonatal lung growth in bronchopulmonary dysplasia.

scholarly journals Effect of N-acetyl cysteine on enterocyte apoptosis and intracellular signalling pathways' response to oxidative stress in weaned piglets

2013 ◽  
Vol 110 (11) ◽  
pp. 1938-1947 ◽  
Author(s):  
Lihui Zhu ◽  
Xuan Cai ◽  
Qi Guo ◽  
Xiaolian Chen ◽  
Suwen Zhu ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Intracellular Signalling ◽  
Signalling Pathways ◽  
Caspase 8 ◽  
Weaned Piglets ◽  
Caspase 9 ◽  
Gene Expressions ◽  
Intracellular Signalling Pathways ◽  
Enterocyte Apoptosis ◽  
Acetyl Cysteine

N-acetyl cysteine (NAC) has been widely used for preventing reactive oxygen species-induced damage. However, little is known as to whether dietary NAC supplementation would alleviate intestinal injury in weaned piglets. The present study evaluated the effect of NAC on enterocyte apoptosis and intracellular signalling pathways' response to weaning stress. The control piglets were normally suckling, and piglets in the weaning and NAC groups were fed the basal diet and basal+NAC diet from 14 to 25 d of age, respectively. Compared with the control piglets, weaning increased cortisol concentrations (P< 0·05), decreased superoxide dismutase and glutathione peroxidase activities (P< 0·05), increased malondialdehyde content (P< 0·05) in serum and enhanced enterocyte apoptosis index (AI) and concentrations of caspase-3, caspase-8 and caspase-9 (P< 0·05). Gene expression analyses indicated that weaning induced apoptosis via Fas signalling and mitochondrial pathways in weaned piglets. Dietary NAC supplementation decreased (P< 0·05) cortisol concentrations and the AI, increased (P< 0·05) antioxidant status in serum and alleviated histopathological changes in the intestine. It also inhibited Fas, caspase-3, caspase-8 and integrin αvβ6 (αvβ6) gene expressions in the NAC-treated piglets. However, no significant decrease (P>0·10) in caspase-3, caspase-8 and caspase-9 concentrations was observed in the NAC group compared with the weaning group. In conclusion, weaning may induce enterocyte apoptosis via the activation of Fas-dependent and mitochondria-dependent apoptosis. Although NAC had no effect on caspase concentrations, it was clearly beneficial for preserving morphological integrity in weaned piglets via the regulation of cell apoptosis and the inhibition of Fas-dependent apoptosis and αvβ6 expression.

scholarly journals HIF-1α Is Associated with Resistance to Hypoxia-Induced Apoptosis in Ameloblastoma

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Katherine Julissa Palma Valladares ◽  
Karolyny Martins Balbinot ◽  
Antonia Taiane Lopes de Moraes ◽  
Maria Sueli da Silva Kataoka ◽  
Aline Maria Pereira Cruz Ramos ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Genetic Interaction ◽  
Direct Interaction ◽  
High Rate ◽  
Signalling Pathways ◽  
Local Behaviour ◽  
Direct Association ◽  
Factor Alpha ◽  
Significant Expression ◽  
Induced Apoptosis

Background. Ameloblastoma (AMB) is a benign odontogenic tumour, with an aggressive local behaviour and a high rate of recurrence. Previous studies have demonstrated that hypoxia-induced factor alpha 1 (HIF-1α) and activated caspase-3 contribute to tumour invasiveness and cytogenesis in ameloblastoma. Hypoxia increases HIF-1α levels, which triggers a number of signalling pathways. This paper aimed to present data in the study of hypoxia-activated signalling pathways that modulate proapoptotic and antiapoptotic events in AMB. Methods. Twenty cases of AMB and ten cases of dental follicle (DF) were used to analyse the immunoexpression of HIF-1α, p53, BNIP3, Bcl-2, IAP-2, GLUT1, and Bax. To contribute to the study, an analysis of expression and genetic interaction was performed using the cell line AME-1. Results. AMB and DF expressed the studied proteins. These proteins showed significantly greater immunoexpression in AMB compared with the DF ( p < 0.05 ). HIF-1α showed an important association with GLUT1, and a positive correlation was observed among p53, Bcl-2, and IAP-2. Transcriptomic analysis showed the significant expression of the studied proteins, and the network generated showed a direct association of HIF-1αF with GLUT1 (SLC2A1), TP53, and LDHA. Interestingly, GLUT1 also exhibited direct interaction with TP53 and LDHA. Conclusion. In AMB tumorigenesis, hypoxia is possibly related to antiapoptotic events, which suggests an important role for HIF-1α, GLUT1, Bcl-2, IAP-2, and possibly p53.

scholarly journals Effect of Supracervical Apposition and Spontaneous Labour on Apoptosis and Matrix Metalloproteinases in Human Fetal Membranes

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Mahalia Chai ◽  
Susan P. Walker ◽  
Clyde Riley ◽  
Gregory E. Rice ◽  
Michael Permezel ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Caspase 3 ◽  
Signalling Pathways ◽  
Fetal Membranes ◽  
Biochemical Characteristics ◽  
Spontaneous Labour ◽  
Distal Site ◽  
Labour Onset ◽  
Expression And Activity ◽  
Human Parturition

Background. Apoptosis and matrix metalloproteinase (MMP-9) are capable of hydrolysing components of the extracellular matrix and weakening the fetal membranes which leads to eventual rupture, a key process of human parturition. The aim of this study was to determine the effect of supracervical apposition and spontaneous labour on apoptosis and MMP-9 in human fetal membranes at term.Methods. Fetal membranes were obtained from term non-labouring supracervical site (SCS) and compared to (i) a paired distal site (DS) or (ii) site of rupture (SOR) after spontaneous labour onset.Results. The expression of the proapoptotic markers Bax, Smac, Fas, FasL, caspase-3, and PARP, was significantly higher in the non-labouring SCS chorion compared to paired DS. Bax, Smac, FasL, caspase-3, and PARP staining was higher in the non-labouring SCS fetal membranes than that in the post-labour SOR. MMP-9 expression and activity were higher in the post-labour SOR fetal membranes compared to non-labouring SCS fetal membranes.Conclusion. Components of the apoptotic signalling pathways and MMP-9 may play a role in rupture and labour. Non-labouring SCS fetal membranes display altered morphology and altered apoptotic biochemical characteristics in preparation for labour, while the laboured SOR displays unique MMP characteristics.

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