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11.
Na,K-ATPase inhibition alters tight junction structure and permeability in human retinal pigment epithelial cells 总被引:2,自引:0,他引:2
Rajasekaran SA Hu J Gopal J Gallemore R Ryazantsev S Bok D Rajasekaran AK 《American journal of physiology. Cell physiology》2003,284(6):C1497-C1507
Na,K-ATPase regulates avariety of transport functions in epithelial cells. In cultures ofhuman retinal pigment epithelial (RPE) cells, inhibition of Na,K-ATPaseby ouabain and K+ depletion decreased transepithelialelectrical resistance (TER) and increased permeability of tightjunctions to mannitol and inulin. Electrophysiological studiesdemonstrated that the decrease in TER was due to an increase inparacellular shunt conductance. At the light microscopy level, thisincreased permeability was not accompanied by changes in thelocalization of the tight junction proteins ZO-1, occludin, andclaudin-3. At the ultrastructural level, increased tight junctionpermeability correlated with a decrease in tight junction membranecontact points. Decreased tight junction membrane contact points andincreased tight junction permeability were reversible inK+-repletion experiments. Confocal microscopy revealed thatin control cells, Na,K-ATPase was localized at both apical andbasolateral plasma membranes. K+ depletion resulted in alarge reduction of apical Na,K-ATPase, and after K+repletion the apical Na,K-ATPase recovered to control levels. Theseresults suggest a functional link exists between Na,K-ATPase and tightjunction function in human RPE cells. 相似文献
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Conventional reversed sural flaps have been used to cover heel defects; however, the experience of the authors indicates that the reach of these flaps falls just short of the critical area to be covered. With the limitation being the location of the flap (the middle third of the leg), the authors thought that if the flap territory were extended proximally, they would have a super flap with immense potential. Nevertheless, the critical question remained, "How far?" The massive earthquake in January of 2001 in Gujarat, India, made medical personnel pressed for time, manpower, resources, and other ancillary supports. The authors were forced to make some innovations in their management of extensive heel defects. On the basis of preexisting anatomic studies, they developed the possibility of using distally based neuroskin flaps of huge dimensions that extend well beyond the conventional confines. The versatility of this extended, reversed, neuro-fasciocutaneous flap in regard to its reliability and safety, despite its huge dimensions, is commendable. The hallmarks of this successful extended sural flap, which the authors used to cover large heel defects, were basically accurate understanding of the anatomy and the use of Doppler to map the perforators and the lesser saphenous vein for inclusion in the lie of the pedicle. The authors share their experience of five cases of difficult heel reconstructions salvaged with this flap, which made them attempt to define maximum flap dimensions that can be harvested. The authors learned that the flap can be extended proximally to include the entire upper one-third of the leg posteriorly, drastically improving its reach and size, without compromising safety. The largest flap used measured 17 x 16 cm, far more than ever reported in the literature. The flaps truly deserve the classification of "super," which is usually reserved for Ponten's flaps. 相似文献
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Is prostate-specific membrane antigen a multifunctional protein? 总被引:5,自引:0,他引:5
Rajasekaran AK Anilkumar G Christiansen JJ 《American journal of physiology. Cell physiology》2005,288(5):C975-C981
Prostate-specific membrane antigen (PSMA) is a metallopeptidase expressed predominantly in prostate cancer (PCa) cells. PSMA is considered a biomarker for PCa and is under intense investigation for use as an imaging and therapeutic target. Although the clinical utility of PSMA in the detection and treatment of PCa is evident and is being pursued, very little is known about its basic biological function in PCa cells. The purpose of this review is to highlight the possibility that PSMA might be a multifunctional protein. We suggest that PSMA may function as a receptor internalizing a putative ligand, an enzyme playing a role in nutrient uptake, and a peptidase involved in signal transduction in prostate epithelial cells. Insights into the possible functions of PSMA should improve the diagnostic and therapeutic values of this clinically important molecule. prostate cancer; receptor; peptidase; endocytosis 相似文献
14.
Das PC Ayyappan S Das BK Jena JK 《Comparative biochemistry and physiology. Toxicology & pharmacology : CBP》2004,138(1):3-10
The effects of 96-h sublethal exposure of nitrite (1, 2, 4, 8 and 10.4 mg l(-1)) on selected enzymatic activities in serum and tissues of fingerlings of catla (Catla catla), rohu (Labeo rohita) and mrigal (Cirrhinus mrigala) were studied for the first time in these species. All three species responded almost identically to nitrite exposure. With increasing nitrite concentration, reduction in activities was observed in acetylcholinesterase (AChE) in brain and liver; alkaline phosphatase (ALP) in serum, brain and gill; and acid phosphatase (ACP) in gill, while progressive increase in alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) activities in brain, gill and serum, and ACP activity in serum and brain was observed. Lactate dehydrogenase (LDH) activity increased in gill, liver, kidney, brain and serum of all three species with increasing nitrite concentration up to 8 mg l(-1) followed by reduction at 10.4 mg l(-1). The study revealed nitrite stress causing alteration in activities of all measured tissue and serum enzymes in the fingerlings, and so stresses the need for proper management of this particular nutrient in water during carp culture. 相似文献
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Ponniah Selvakumar Tori A Owens Justin M David Nicholas J Petrelli Brock C Christensen Ashakumary Lakshmikuttyamma Ayyappan K Rajasekaran 《Epigenetics》2014,9(4):579-586
The Na,K-ATPase or sodium pump carries out the coupled extrusion of Na+ and uptake of K+ across the plasma membranes of cells of most higher eukaryotes. We have shown earlier that Na,K-ATPase-β1 (NaK-β) protein levels are highly reduced in poorly differentiated kidney carcinoma cells in culture and in patients' tumor samples. The mechanism(s) regulating the expression of NaK-β in tumor tissues has yet to be explored. We hypothesized that DNA methylation plays a role in silencing the NaK-β gene (ATP1B1) expression in kidney cancers. In this study, to the best of our knowledge we provide the first evidence that ATP1B1 is epigenetically silenced by promoter methylation in both renal cell carcinoma (RCC) patients’ tissues and cell lines. We also show that knockdown of the von Hippel-Lindau (VHL) tumor suppressor gene in RCC cell lines results in enhanced ATP1B1 promoter AT hypermethylation, which is accompanied by reduced expression of NaK-β. Furthermore, treatment with 5-Aza-2′-deoxycytidine rescued the expression of ATP1B1 mRNA as well as NaK-β protein in these cells. These data demonstrate that promoter hypermethylation is associated with reduced NaK-β expression, which might contribute to RCC initiation and/or disease progression. 相似文献
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Kezia Lizardo Janeesh Plakkal Ayyappan Min-Hui Cui Rashmi Balasubramanya Linda A. Jelicks Jyothi F. Nagajyothi 《Microbes and infection / Institut Pasteur》2019,21(1):63-71
Infection with Trypanosoma cruzi, the etiologic agent in Chagas disease, may result in heart disease. Over the last decades, Chagas disease endemic areas in Latin America have seen a dietary transition from the traditional regional diet to a Western style, fat rich diet. Previously, we demonstrated that during acute infection high fat diet (HFD) protects mice from the consequences of infection-induced myocardial damage through effects on adipogenesis in adipose tissue and reduced cardiac lipidopathy. However, the effect of HFD on the subsequent stages of infection – the indeterminate and chronic stages – has not been investigated. To address this gap in knowledge, we studied the effect of HFD during indeterminate and chronic stages of Chagas disease in the mouse model. We report, for the first time, the effect of HFD on myocardial inflammation, vasculopathy, and other types of dysfunction observed during chronic T. cruzi infection. Our results show that HFD perturbs lipid metabolism and induces oxidative stress to exacerbate late chronic Chagas disease cardiac pathology. 相似文献
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Postnatal ethanol exposure alters levels of 2‐arachidonylglycerol‐metabolizing enzymes and pharmacological inhibition of monoacylglycerol lipase does not cause neurodegeneration in neonatal mice 下载免费PDF全文
Shivakumar Subbanna Delphine Psychoyos Shan Xie Balapal S. Basavarajappa 《Journal of neurochemistry》2015,134(2):276-287
The consumption of ethanol by pregnant women may cause neurological abnormalities, affecting learning and memory processes in children, and are collectively described as fetal alcohol spectrum disorders. However, the molecular mechanisms underlying these changes are still poorly understood. In our previous studies, we found that ethanol treatment of postnatal day 7 (P7) mice significantly enhances the anandamide levels but not the 2‐arachidonylglycerol (2‐AG) levels and induces widespread neurodegeneration, but the reason for the lack of significant effects of ethanol on the 2‐AG level is unknown. In this study, we examined developmental changes in diacylglycerol lipase‐α, β (DAGL‐α and β) and monoacylglycerol lipase (MAGL). We found that the levels of these proteins were significantly higher in adult brains compared to those detected early in brain development. Next, we examined the influence of P7 ethanol treatment on these enzymes, finding that it differentially altered the DAGL‐α protein and mRNA levels but consistently enhanced those of the DAGL‐β. Interestingly, the ethanol treatment enhanced MAGL protein and mRNA levels. Inhibition of MAGL with KML29 failed to induce neurodegeneration in P7 mice. Collectively, these findings suggest that ethanol significantly activates DAGL‐β and MAGL in the neonatal brain, resulting in no net change in 2‐AG levels.
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CB1‐receptor knockout neonatal mice are protected against ethanol‐induced impairments of DNMT1, DNMT3A,and DNA methylation 下载免费PDF全文
Nagaraja N. Nagre Shivakumar Subbanna Madhu Shivakumar Delphine Psychoyos Balapal S. Basavarajappa 《Journal of neurochemistry》2015,132(4):429-442
The significant consequences of ethanol use during pregnancy are neurobehavioral abnormalities involving hippocampal and neocortex malfunctions that cause learning and memory deficits collectively named fetal alcohol spectrum disorder. However, the molecular mechanisms underlying these abnormalities are still poorly understood and therefore warrant systematic research. Here, we document novel epigenetic abnormalities in the mouse model of fetal alcohol spectrum disorder. Ethanol treatment of P7 mice, which induces activation of caspase 3, impaired DNA methylation through reduced DNA methyltransferases (DNMT1 and DNMT3A) levels. Inhibition of caspase 3 activity, before ethanol treatment, rescued DNMT1, DNMT3A proteins as well as DNA methylation levels. Blockade of histone methyltransferase (G9a) activity or cannabinoid receptor type‐1 (CB1R), prior to ethanol treatment, which, respectively, inhibits or prevents activation of caspase 3, rescued the DNMT1 and DNMT3A proteins and DNA methylation. No reduction of DNMT1 and DNMT3A proteins and DNA methylation was found in P7 CB1R null mice, which exhibit no ethanol‐induced activation of caspase 3. Together, these data demonstrate that ethanol‐induced activation of caspase 3 impairs DNA methylation through DNMT1 and DNMT3A in the neonatal mouse brain, and such impairments are absent in CB1R null mice. Epigenetic events mediated by DNA methylation may be one of the essential mechanisms of ethanol teratogenesis.