Sistema Solar: Planetas Clássicos

O conhecimento curricular de Astronomia para surdos, não pode ser empobrecido, subtraído, fragmentado, mas sim formulado para corresponder a sua identidade de cognição, sem distanciar-se, porém, do direito inalienável a tudo que devem conhecer. Métodos de ensino não podem ser únicos para todos e, um sistema educacional que não revela estas diferenças está fadado em provocar a exclusão destes educandos por considerá-los inaptos, intelectualmente. Sendo assim, ao organizar o conteúdo que será trabalhado em sala de aula, o professor terá sempre em mente o tema Sistema Solar /Planetas Clássicos. Este tema está diretamente ligado a outros temas, permitindo ao aluno surdo fazer parte desse todo tão complexo que é o Universo em que vivemo

Nicotine Induces Podocyte Apoptosis through Increasing Oxidative Stress

Cigarette smoking plays an important role in the progression of chronic kidney disease (CKD). Nicotine, one of the major components of cigarette smoking, has been demonstrated to increase proliferation of renal mesangial cells. In this study, we examined the effect of nicotine on podocyte injury.To determine the expression of nicotinic acetylcholine receptors (nAChR subunits) in podocytes, cDNAs and cell lysate of cultured human podocytes were used for the expression of nAChR mRNAs and proteins, respectively; and mouse renal cortical sections were subjected to immunofluorescant staining. We also studied the effect of nicotine on podocyte nephrin expression, reactive oxygen species (ROS) generation (via DCFDA loading followed by fluorometric analysis), proliferation, and apoptosis (morphologic assays). We evaluated the effect of nicotine on podocyte downstream signaling including phosphorylation of ERK1/2, JNK, and p38 and established causal relationships by using respective inhibitors. We used nAChR antagonists to confirm the role of nicotine on podocyte injury.Human podocytes displayed robust mRNA and protein expression of nAChR in vitro studies. In vivo studies, mice renal cortical sections revealed co-localization of nAChRs along with synaptopodin. In vitro studies, nephrin expression in podocyte was decreased by nicotine. Nicotine stimulated podocyte ROS generation; nonetheless, antioxidants such as N-acetyl cysteine (NAC) and TEMPOL (superoxide dismutase mimetic agent) inhibited this effect of nicotine. Nicotine did not modulate proliferation but promoted apoptosis in podocytes. Nicotine enhanced podocyte phosphorylation of ERK1/2, JNK, and p38, and their specific inhibitors attenuated nicotine-induced apoptosis. nAChR antagonists significantly suppressed the effects of nicotine on podocyte.Nicotine induces podocyte apoptosis through ROS generation and associated downstream MAPKs signaling. The present study provides insight into molecular mechanisms involved in smoking associated progression of chronic kidney disease

Modulation of renin angiotensin system predominantly alters sclerotic phenotype of glomeruli in HIVAN

HIV-associated nephropathy (HIVAN) is a common complication of HIV-1 infection in patients with African ancestry in general and with APOL1 gene risk variants in particular. Although collapsing glomerulopathy is considered a hallmark of HIVAN, significant numbers of glomeruli in patients with HIVAN also display other variants of focal segmental glomerulosclerosis (FSGS). We propose that collapsed glomeruli as well as glomeruli with other variants of FSGS are manifestations of HIVAN and their prevalence depends on associated host factors. We explored the role of the renin-angiotensin system (RAS) in the manifestation of any specific glomerular phenotype in HIVAN. To evaluate the role of the RAS we have used a genetically engineered mouse model of HIVAN (Tg26) with two and four copies of angiotensinogen (Agt) gene (Tg26/Agt2 and Tg26/Agt4). In Tg26/Agt2, 1 out of 6 glomeruli exhibited sclerosed phenotype, whereas 1 out of 25 glomeruli displayed collapsed phenotype; on the other hand, in Tg26/Agt4, 1 out of 3 glomeruli exhibited sclerotic phenotype and only 1 out of 7 glomeruli showed collapsed phenotype. To inhibit the effect of RAS, Tg26/Agt2 were administered captopril, aliskiren, aliskiren plus captopril or aliskiren plus telmisartan by miniosmotic pumps for 4 weeks. In all experimental groups there was a significant reduction in percentage of sclerosed glomeruli and only minimal reduction in collapsed glomeruli compared to normal saline receiving Tg26/Agt2. These findings suggest that the manifestation of the sclerosed phenotype in HIVAN is predominantly dependent on activation of the RAS

Hyperglycemia enhances kidney cell injury in HIVAN through down-regulation of vitamin D receptors

In the present study, we evaluated the effect of short term hyperglycemia on renal lesions in a mouse model (Tg26) of HIV-associated nephropathy (HIVAN). Control and Tg26 mice in groups (n=6) were administered either normal saline (FVBN or Tg) or streptozotocin (FVBN+STZ or Tg26 + STZ). After two weeks, biomarkers were collected and kidneys were harvested. FVBN+ STZ and Tg26 + STZ displayed elevated serum glucose levels when compared to FVBN and Tg26 respectively. Tg26 +STZ displayed elevated (P<0.05) blood urea nitrogen (BUN) levels (P<0.05) and enhanced (P<0.01) proteinuria when compared to Tg26. Tg26 + STZ displayed enhanced (P<0.001) number of sclerotic glomeruli and microcysts vs. Tg26. Renal tissues of Tg26 displayed down regulation of vitamin D receptor (VDR) expression and enhanced Ang II production when compared to FVBN mice. Hyperglycemia exacerbated down regulation of VDR and production of Ang II in FVBN and Tg mice. Hyperglycemia increased kidney cell reactive oxygen species (ROS) production and oxidative DNA damage in both FVBN and Tg26 mice. In in vitro studies, HIV down regulated podocyte VDR expression and also enhanced renin angiotensin system activation. In addition, both glucose and HIV stimulated kidney cell ROS generation and DNA damage and compromised DNA repair; however, tempol (superoxide dismutase mimetic), losartan (Ang II blocker) and EB1089 (VDR agonist) provided protection against DNA damaging effects of glucose and HIV. These findings indicated that glucose activated the RAS and inflicted oxidative stress-mediated DNA damage via down regulation of kidney cell VDR expression in HIV milieu both in vivo and in vitro

Epigenetic Modulation of Human Podocyte Vitamin D Receptor in HIV Milieu

HIV has been reported to induce podocyte injury through down regulation of vitamin D receptor (VDR) and activation of renin angiotensin system (RAS); however, the involved mechanism is not clear. Since HIV has been reported to modulate gene expression via epigenetic phenomena, we asked whether epigenetic factors are contributing to down regulation of VDR. Kidney cells in HIV transgenic mice as well as HIV-infected podocytes (HIV/HPs) displayed enhanced expression of SNAIL, a repressor of VDR. To elucidate the mechanism, we studied the effect of HIV on expression of molecules involved in SNAIL repressor complex formation and demonstrated that HIV enhancesexpression of histone deacetylase (HDAC) 1, DNA methyl transferase (DNMT) 3b and DNMT1. 293T cells, when stably transfected with SNAIL (SNAIL/293T), displayed suppressed transcription and translation of VDR. In SNAIL/293T cells, co-immunoprecipitation studies revealed the association of HDAC1, DNMT3b, DNMT1, and mSin3A with SNAIL. Chromatin immunoprecipitation (ChIP) experiments confirmed the presence of the SNAIL repressor complex at the VDR promoter. Consistent with the enhanced DNA methyl transferase expression in HIV/HPs, there was an increased CpG methylation at the VDR promoter. ChIP assay confirmed occurrence of H3K4 trimethylation on SNAIL promoter. Neither VDR agonist (VDA) nor an HDAC inhibitor (HDACI) nor demethylating agent (DAC) individually could optimally upregulate VDR in HIV milieu. However, VDA and HDACI when combined were successful in de-repressing VDR expression. Our findings demonstrate that SNAIL recruits multiple chromatin enzymes to form a repressor complex in HIV milieu which down regulates VDR expression

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Nicotine decrease nephrin expression in podocyte.

<p>Differentiated human podocytes were treated with nicotine (1 and10 μM) for 48 h. Cell lysates were then collected and subjected for Western blotting to detect nephrin expression. A. Representative gels are displayed. B. Quantification of the expression of nephrin in <b>A,</b> and the results (mean ± SD) represent three independent samples. * p < 0.05 compared with control (0 μM).</p

MAPKs regulated nicotine-induced podocyte apoptosis.

<p>A. Differentiated Human podocytes were starved in serum free medium for 12 h, and then 0.1 μM nicotine was added. Cell lysates were collected at different time points, and Western blotting was performed to detect the phosphor-ERK1/2, JNK, and p38. Total proteins and actin were used as loading control. <b>B</b>. Human podocytes were pretreated with of PD98059 (PD, 5 μM), SB203580 (SB, 3 μM), or SP600125 (SP, 5 μM) for 1 h before 10 μM nicotine was added. After incubation at 37°C for another 48 h, apoptotic cells were then determined and counted by using Hoechst staining. Results (mean ± SD) were calculated from 20 pictures of each treatment. * p < 0.05 compared with blank control, while # p < 0.05 compared with morphine treatment alone.</p

Nicotine treatment affects apoptosis related proteins in podocyte.

<p>Differentiated human podocytes were treated with nicotine (0.1–10 μM) for 24 h. Cell lysates were then collect and were subjected for Western blotting. A. Representative results were selected to show the Western blottings. B-D. Quantification of the expression of Bcl-2 (<b>B</b>), Bax (<b>C</b>), and Cleaved caspase-3 (<b>D</b>) in <b>A,</b> and the results (mean ± SD) represent three independent samples. * p < 0.05 compared with control (0 μM).</p

Nicotine increases ROS generation in podocyte.

<p>A. Differentiated human podocytes were treated with 0.01 to 10 μM nicotine for 12 h, and were labeled with DCFH for 30 min. After washing with PBS, the cells were incubated at room temperature, and the ROS generation was determined after different periods of time. * p < 0.05, ** p < 0.01, and *** p < 0.001 compared with control (0 μM). B. Differentiated human podocytes were pre-treated with VAS2870 (10 μM) for 1 h, followed by treatment with 10 μM nicotine for another 12 h. Subsequently, the cells were labeled with DCFH and the ROS generation was determined at 1 hour as described above. *p< 0.05 compared with control (0 μM) while #p<0.05 compared with nicotine treatment alone.</p