This study reports the consequences of knocking out NADPH oxidase 4 (Nox4) upon the development of hypertension and kidney injury in the Dahl salt-sensitive (SS) rat. Zinc finger nuclease injection of single cell SS embryos was used to create an 8 base-pair frame-shift deletion of Nox4 resulting in a loss of the ~68 kD band in Western blot analysis of renal cortical tissue of the SSNox4−/− rats. SSNox4−/− rats exhibited a significant reduction of salt-induced hypertension compared to SS rats after 21 days of 4.0% NaCl diet (134±5 vs 151±3 mmHg in SS) and a significant reduction of albuminuria, tubular casts, and glomerular injury. Optical fluorescence 3D cryoimaging revealed significantly higher redox ratios (NADH/FAD) in the kidneys of SSNox4−/− rats even when fed the 0.4% NaCl diet indicating greater levels of mitochondrial electron transport chain metabolic activity and reduced oxidative stress compared to SS rats. Prior to the development of hypertension, RNA expression levels of NADPH oxidase subunits Nox2, p67phox, and p22phox were found to be significantly lower (p<0.05) in SSNox4−/− compared to SS rats in the renal cortex. Thus the mutation of Nox4 appears to modify transcription of a number of genes in ways that contribute to the protective effects observed in the SSNox4−/− rats. We conclude that the reduced renal injury and attenuated blood pressure response to high salt in the SSNox4−/− rat could be the result of multiple pathways including gene transcription, mitochondrial energetics, oxidative stress, and protein matrix production impacted by the knock out of Nox4.
Most of the physiological processes are controlled by the small RNAs in several organisms including plants. A huge database exists on one type of small RNA, i.e., microRNAs (miRs) identified from diverse species. However, the processes of data-mining of miRs in most of the species are still incomplete. Rice feeds the hungry trillions and hence understanding its developmental processes as well as its stress biology, which might be largely controlled by the small RNA pathways, is certainly a worthwhile task. Here, we report the cloning and identification of approximately 40 new putative miRs from local basmati rice variety in accordance to the annotation suggested by Meyers et al. (Plant Cell 20:3186-3190, 2008). About 23 sequences were derived from rice exposed to salt stress while 18 were derived from rice infected with tungro virus. A few of these putative miRs were common to both. Our data showed that at least two of these miRs were up-regulated in response to both abiotic and biotic stresses. The miR target predictions indicate that most of the putative miRs target specific metabolic processes. The up-regulation of similar miRs in response to two entirely different types of stresses suggests a converging functional role of miRs in managing various stresses. Our findings suggest that more rice miRs need to be identified and a thorough understanding of the function of such miRs will help unravel the mysteries of rice stress biology.
A 1.37 Mbp region of chromosome 13 previously identified by exclusion mapping was consistently associated with a reduction of salt-induced hypertension in the Dahl salt-sensitive (SS) rat. This region contained five genes that were introgressed from the salt-insensitive Brown Norway (BN) rat. The goal of the present study was to further narrow that region to identify the gene(s) most likely to protect from salt-induced hypertension. The studies yielded a subcongenic SS rat strain containing a 0.71 Mbp insert from BN (26-P strain) in which salt-induced hypertension was reduced by 24 mmHg. The region contained two protein-coding genes (Astn1 and Pappa2) and a microRNA (miR-488). Pappa2 mRNA in the renal cortex of the protected 26-P was 6- to 10-fold greater than in SS fed a 0.4% NaCl diet but was reduced to levels observed in SS when fed 8.0% NaCl diet for 7 days. Compared with brain nuclei (NTS, RVLM, CVLM) and the adrenal gland, Pappa2 in the renal cortex was the only gene found to be differentially expressed between SS and 26-P and that responded to changes of salt diet. Immunohistochemistry studies found Pappa2 localized in the cytosol of the epithelial cells of the cortical thick ascending limbs. In more distal segments of the renal tubules, it was observed within tubular lumens and most notably bound to the apical membranes of the intercalated cells of collecting ducts. We conclude that we have identified a variant form of Pappa2 that can protect against salt-induced hypertension in the Dahl S rat.
In addition to their encapsidation function, viral coat proteins (CP) contribute to viral life cycle in many different ways. The CPs of the geminiviruses are responsible for intra- as well as inter-plant virus transmission and might determine the yield of viral DNA inside the infected tissues by either packaging the viral DNA or interfering with the viral replicative machinery. Since the cognate Rep largely controls the rolling circle replication of geminiviral DNA, the interaction between Rep and CP might be worthwhile to examine for elucidation of CP-mediated control of the viral DNA copy number. Here a reasonably strong interaction between Rep and CP of the geminivirus Mung bean yellow mosaic India virus is reported. The domain of interaction has been mapped to a central region of Rep. The replication initiation activity of Rep, i.e., its nicking and closing function, is down regulated by CP. This report highlights how CP could be important in controlling geminiviral DNA replication.
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