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111.
Manganese porphyrin reduces renal injury and mitochondrial damage during ischemia/reperfusion 总被引:2,自引:2,他引:0
Saba H Batinic-Haberle I Munusamy S Mitchell T Lichti C Megyesi J MacMillan-Crow LA 《Free radical biology & medicine》2007,42(10):1571-1578
Renal ischemia/reperfusion (I/R) injury often occurs as a result of vascular surgery, organ procurement, or transplantation. We previously showed that renal I/R results in ATP depletion, oxidant production, and manganese superoxide dismutase (MnSOD) inactivation. There have been several reports that overexpression of MnSOD protects tissues/organs from I/R-related damage, thus a loss of MnSOD activity during I/R likely contributes to tissue injury. The present study examined the therapeutic benefit of a catalytic antioxidant, Mn(III) meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin (MnTnHex-2-PyP(5+)), using the rat renal I/R model. This was the first study to examine the effects of MnTnHex-2-PyP(5+) in an animal model of oxidative stress injury. Our results showed that porphyrin pretreatment of rats for 24 h protected against ATP depletion, MnSOD inactivation, nitrotyrosine formation, and renal dysfunction. The dose (50 microg/kg) used in this study is lower than doses of various types of antioxidants commonly used in animal models of oxidative stress injuries. In addition, using novel proteomic techniques, we identified the ATP synthase-beta subunit as a key protein induced by MnTnHex-2-PyP(5+) treatment alone and complex V (ATP synthase) as a target of injury during renal I/R. These results showed that MnTnHex-2-PyP(5+) protected against renal I/R injury via induction of key mitochondrial proteins that may be capable of blunting oxidative injury. 相似文献
112.
Guz G Oz E Lortlar N Ulusu NN Nurlu N Demirogullari B Omeroglu S Sert S Karasu C 《Amino acids》2007,32(3):405-411
Summary. Ischemia-reperfusion (I/R) injury is one of the most common causes of renal dysfunction. Taurine is an endogenous antioxidant
and a membrane-stabilizing, intracellular, free beta-amino acid. It has been demonstrated to have protective effects against
I/R injuries to tissues other than kidney. The aim of this study was to determine whether taurine has a beneficial role in
renal I/R injury. Forty Wistar-Albino rats were allocated into four groups as follows: sham, taurine, I/R, and I/R + taurine.
Taurine 7.5 mg/kg was given intra-peritoneally to rats in the groups taurine and I/R + taurine. Renal I/R was achieved by
occluding the renal arteries bilaterally for 40 min, followed by 6 h of reperfusion. Immediately thereafter, blood was drawn
and tissue samples were harvested to measure 1) serum levels of BUN and creatinine; 2) serum and/or tissue levels of malondialdehyde
(MDA), glutathione (GSH), glucose 6-phosphate dehydrogenase (G-6PD), 6-phosphogluconate dehydrogenase (6-PGD) and glutathione
reductase (GSH-red); 3) renal morphology; and 4) immunohistochemical staining for P-selectin. Taurine administration reduced
I/R-induced increases in serum BUN and creatinine, and serum and tissue MDA levels (p < 0.05). Additionally, taurine lessened
the reductions in serum and tissue glutathione levels secondary to I/R (p < 0.05). Taurine also attenuated histopathologic
evidence of renal injury, and reduced I/R-induced P-selectin immunoreactivity (p < 0.05). Overall, then, taurine administration
appears to reduce the injurious effects of I/R on kidney. 相似文献
113.
Distribution of anticancer antibiotic daunomycin in the rat heart and kidney revealed by immunocytochemistry using monoclonal antibodies 总被引:3,自引:3,他引:0
Two monoclonal antibodies (ADM-1-11 and 79-31 mAbs) were raised against daunomycin (DM) conjugated to bovine serum albumin
via the cross-linker N-(gamma-maleimidobutyryloxy)succinimide. The monoclonal antibodies (mAbs) specifically detected DM as well as its analogs
doxorubicin and epirubicin, but did not react with other anticancer antibiotics, including pepleomycin, mitomycin C, and actinomycin
D. The mAbs reacted strongly with glutaraldehyde-conjugated DM in an enzyme linked immunosorbent assay (ELISA) used as a model
system for immunocytochemistry as well as in appropriately pretreated sections of tissues from animals injected with DM. No
staining occurred in tissues from uninjected animals. In order to perform DM ICC a number of tissue treatment conditions critical
to the detection of low molecular weight substances were employed. Uptake of DM was studied in rats after a single i.v. or
i.p. administration of the drug. In the heart, accumulation of DM occurred in nuclei and in the cytoplasm. In the kidney,
DM immunoreactivity accumulated in all segments of the nephron except for the proximal tubules. Since the proximal tubules
are known to be where a variety of transport systems including P-glycoprotein (Pgp) and organic anion-transporting polypeptides
(OATPs) in drug interactions occur, the absence of DM accumulation in these segments may reflect a transport phenomenon depending
upon such transporters. The availability of methods to study sites of accumulation of DM offers possibilities for understanding
toxic side effects of this drug on the heart and kidney. Moreover, the immunocytochemical methodology developed may prove
useful for the localization of other low molecular weight drugs that can be fixed in situ by glutaraldehyde. 相似文献
114.
《Journal of molecular biology》2022,434(4):167290
In the last several decades, apoptosis interference has been considered clinically irrelevant in the context of renal injury. Recent discovery of programmed necrotic cell death, including necroptosis, ferroptosis, and pyroptosis refreshed our understanding of the role of cell death in kidney disease. Pyroptosis is characterized by a lytic pro- inflammatory type of cell death resulting from gasdermin-induced membrane permeabilization via activation of inflammatory caspases and inflammasomes. The danger-associated molecular patterns (DAMPs), alarmins and pro-inflammatory cytokines are released from pyroptotic cells in an uncontrolled manner, which provoke inflammation, resulting in secondary organ or tissue injuries. The caspases and inflammasome activation-related proteins and pore-forming effector proteins known as GSDMD and GSDME have been implicated in a variety of acute and chronic microbial and non-microbial kidney diseases. Here, we review the recent advances in pathological mechanisms of pyroptosis in kidney disease and highlight the potential therapeutic strategies in future. 相似文献
115.
The kidney is vulnerable to hypoxia, and substantial efforts have been made to ameliorate renal ischemic injury secondary to pathological conditions. Stimulation of the nitrate–nitrite–nitric oxide pathway is associated with renal and cardiovascular protection in disease models, but less is known about the vascular effects during renal ischemia. This study was aimed at investigating the vascular effects of nitrite in the kidney during normoxic and ischemic conditions. Using a multiwire myograph system, we assessed nitrite-mediated relaxation (10−9–10−4 mol/L) in isolated and preconstricted renal interlobar arteries from C57BL/6 mice under normal conditions (pO2 13 kPa; pH 7.4) and with low oxygen tension and low pH to mimic ischemia (pO2 3 kPa; pH 6.6). Xanthine oxidoreductase expression was analyzed by quantitative PCR, and production of reactive nitrogen species was measured by DAF-FM DA fluorescence. During normoxia significant vasodilatation (15±3%) was observed only at the highest concentration of nitrite, which was dependent on NO–sGC–cGMP signaling. The vasodilatory responses to nitrite were greatly sensitized and enhanced during hypoxia with low pH, demonstrating significant dilatation (11±1%) already in the physiological range (10−8 mol/L), with a maximum response of 27±2% at 10−4 mol/L. In contrast to normoxia, and to that observed with a classical NO donor (DEA NONOate), this sensitization was independent of sGC–cGMP signaling. Moreover, inhibition of various enzymatic systems reported to reduce nitrite in other vascular beds, i.e., aldehyde oxidase (raloxifene), aldehyde dehydrogenase (cyanamide), and NO synthase (L-NAME), had no effect on the nitrite response. However, inhibition of xanthine oxidoreductase (XOR; febuxostat or allopurinol) abolished the sensitized response to nitrite during hypoxia and acidosis. In conclusion, in contrast to normoxia, nitrite exerted potent vasorelaxation during ischemic conditions already at physiological concentrations. This effect was dependent on functional XOR but independent of classical downstream signaling by sGC–cGMP. 相似文献
116.
117.
Layton AT 《Mathematical biosciences》2005,197(2):211-230
The organization of tubules and blood vessels in the quail medullary cone is highly structured. This structural organization may result in preferential interactions among tubules and vessels, interactions that may enhance urine concentrating capability. In this study, we formulate a model framework for the urine concentrating mechanism of the quail kidney. The model simulates preferential interactions among renal tubules by representing two concentric cores and by specifying the fractions of tubules assigned to each of the concentric cores. The model equations are based on standard expressions for transmural transport and on solute and water conservation. Model results suggest that the preferential interactions among tubules enhance the urine concentration capacity of short medullary cones by reducing the diluting effect of the descending limbs on the region of the interstitium where the collecting ducts are located; however, the effects on longer cones are unclear. 相似文献
118.
The purpose of this work was to assess the effect of oligomycin on the mitochondrial membrane permeability transition. The antibiotic was found to strengthen cyclosporin A (CSA)-induced protection of non-specific permeability, which is triggered by a matrix Ca2+ load in the absence of ADP. Oligomycin also reinforced the protective effect of CSA on carboxyatractyloside-induced pore opening in the absence of ADP, but failed to do so in mitochondria incubated under anaerobic conditions or after addition of CCCP. Analyzing the efflux of matrix Ca2+, we found that mitochondrial swelling and the collapse of the transmembrane electric gradient coincided with membrane leakage. The effects of the antibiotic were observed in phosphate-containing media but not in the presence of acetate. Furthermore, N-ethylmaleimide hindered the protective effect of oligomycin-CSA. In addition, the matrix phosphate concentration increased concurrently with a diminution in the matrix-free fraction of Ca2+. We concluded that oligomycin increases phosphate uptake by stimulating the phosphate-/OH- exchange reaction. 相似文献
119.
Zaochang?LiuEmail author Byong-Jin?Park Akira?Kanno Toshiaki?Kameya 《Molecular breeding : new strategies in plant improvement》2005,16(3):189-197
An efficient gene transfer system without tissue culture steps was developed for kidney bean by using sonication and vacuum
infiltration assisted, Agrobacterium-mediated transformation. Transgenic kidney bean with a group 3 lea (late embryogenesis abundant) protein gene from Brassica napus was produced through this approach. Among 18 combinations of transformation methods, Agrobacterium-mediated transformation combined with 5 min sonication and 5 min vacuum infiltration turned to be optimal, resulting in the
highest transformation efficiency. Transgenic kidney bean plants demonstrated enhanced growth ability under salt and water
deficit stress conditions. The increased tolerance was also reflected by delayed development of damage symptoms caused by
drought stress. Transgenic lines with high level of lea gene expression showed higher stress tolerance than lines with lower expression level. Stress tolerance of transgenic kidney
bean correlated much better with lea gene expression levels than with gene integration results. There is no prior report on the production of transgenic kidney
bean using both ultrasonic and vacuum infiltration assisted, Agrobacterium-mediated transformation. 相似文献
120.
Cao Y Baig MR Hamm LL Wu K Simon EE 《Biochemical and biophysical research communications》2005,328(2):560-566
Migration of human proximal tubule cells (HKC-5) was stimulated by epidermal growth factor (EGF), hepatocyte growth factor (HGF), and insulin-like growth factor-1 (IGF-1). Integrin signaling via phosphorylation of focal adhesion kinase (FAK) appears to play a central role in cell migration. Once stimulated, FAK undergoes autophosphorylation at tyrosine (Y) 397, followed by phosphorylation of several sites including Y576/Y577 which increases FAK's kinase activity, as well as at Y407, Y861, and Y925. EGF, HGF, and IGF-1 stimulate FAK phosphorylation in various cells. We showed that endothelin stimulated phosphorylation of Y397 in fibroblasts but not HKC-5 cells. After EGF stimulation, HKC-5 cells showed no change in tyrosine phosphorylation at FAK Y397, 407, 576, 861, or 925. Similarly, HGF and IGF-1 did not stimulate the phosphorylation of FAK Y397 in HKC-5 cells. Further, after inhibition of FAK expression by siRNA, cell migration was similar to cells treated with non-target siRNA and responded to EGF with increased migration. Thus, in proximal tubule cells, stimulation of cell migration by growth factors was independent of augmented FAK tyrosine phosphorylation. 相似文献