RESUMO
Endometrial and cervical cancer are among the most frequently diagnosed malignancies globally. Nitric oxide receptor-soluble guanylyl cyclase (sGC) is a heterodimeric enzyme composed of two subunits, α1 and ß1. Previously we showed that sGCα1 subunit promotes cell survival, proliferation, and migration, but the role of sGCß1 subunit has not been addressed. The aim of the present work was to study the impact of sGCß1 restoration in proliferation, survival, migration, and cell signaling in endometrial and cervical cancer cells. We found that sGCß1 transcript levels are reduced in endometrial and cervical tumors vs normal tissues. We confirmed nuclear enrichment of sGCß1, unlike sGCα1. Overexpression of sGCß1 reduced cell viability and augmented apoptotic index. Cell migration and invasion were also negatively affected. All these sGCß1-driven effects were independent of sGC enzymatic activity. sGCß1 reduced the expression of epithelial-to-mesenchymal transition factors such as N-cadherin and ß-catenin and increased the expression of E-cadherin. sGCß1 impacted signaling in endometrial and cervical cancer cells through significant downregulation of Akt pathway affecting some of its main targets such as GSK-3ß and c-Raf. Our results show for the first time that sGCß1 exerts several antiproliferative actions in ECC-1 and HeLa cell lines by targeting key regulatory pathways.
RESUMO
Aquaporin-9 (AQP9) expression is significantly increased in preeclamptic placentas. Since feto-maternal water transfer is not altered in preeclampsia, the main role of AQP9 in human placenta is unclear. Given that AQP9 is also a metabolite channel, we aimed to evaluate the participation of AQP9 in lactate transfer across the human placenta. Explants from normal term placentas were cultured in low glucose medium with or without L-lactic acid and in the presence and absence of AQP9 blockers (0.3 mM HgCl2 or 0.5 mM Phloretin). Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and lactate dehydrogenase release. Apoptotic indexes were analyzed by Bax/Bcl-2 ratio and Terminal Deoxynucleotidyltransferase-Mediated dUTP Nick-End Labeling assay. Heavy/large and light/small mitochondrial subpopulations were obtained by differential centrifugation, and AQP9 expression was detected by Western blot. We found that apoptosis was induced when placental explants were cultured in low glucose medium while the addition of L-lactic acid prevented cell death. In this condition, AQP9 blocking increased the apoptotic indexes. We also confirmed the presence of two mitochondrial subpopulations which exhibit different morphologic and metabolic states. Western blot revealed AQP9 expression only in the heavy/large mitochondrial subpopulation. This is the first report that shows that AQP9 is expressed in the heavy/large mitochondrial subpopulation of trophoblasts. Thus, AQP9 may mediate not only the lactic acid entrance into the cytosol but also into the mitochondria. Consequently, its lack of functionality in preeclamptic placentas may impair lactic acid utilization by the placenta, adversely affecting the survival of the trophoblast cells and enhancing the systemic endothelial dysfunction.
RESUMO
The effect of plant extracts (PE; artichoke, celery, beet, onion, garlic, spinach, avocado, oats, and parsley) in the diet of growing pigs under heat stress was investigated. Parameters included growth performance, blood constituents, carcass characteristics, organ percentage, quality and sensory appraisal of the pork. The study was performed during the Mexican summer, using 60 pigs. Treatments included the control, to which 0.1% PE, and 0.15% PE were added. The use of PE (0.1 and 0.15%) generated an increase in the average daily gain (ADG, by 10.0% for both treatments), and final live weight (LW, by 6.3% and 6.8%) (p < 0.05). The level of blood albumin at 95 kg was higher when supplementing with 0.1% PE (p < 0.05). At 120 kg LW, creatine kinase values showed a tendency to be different (p = 0.07). Carcass weight increased (p < 0.05) when adding PE. Supplementation with 0.1% PE decreased (p < 0.05) the red/green (a *) hue of the meat, whereas supplementation with 0.1% and 0.15% PE increased the yellow/blue (b *) hue (p < 0.05). The addition of PE improves pig growth performance, and carcass weight by reducing the negative effects of heat stress, without markedly modifying blood constituents, meat quality, and sensory attributes of the pork.