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Xia Cao

Publications and source records attributed to Xia Cao.

At least 19 recordsLinked to original sources
PubMed2007

CCR7, CCR8, CCR9 and CCR10 in the mouse hippocampal CA1 area and the dentate gyrus during and after pilocarpine-induced status epilepticus.

The present study showed CCR7, CCR8, CCR9 and CCR10 in the normal Swiss mouse hippocampus at both protein and mRNA levels. CCR7, CCR9 and CCR10 were mainly localized in hippocampal principal cells and some interneurons. CCR9 was also found in the mossy fibres and/or terminals, suggesting an axonal or presynaptic localization, and CCR10 in apical dendrites of pyramidal neurons in the CA1 area. CCR8 was observed in interneurons. Double-labelling immunocytochemistry revealed that most of calbindin (CB)-, calretinin (CR)- and parvalbumin (PV)-immunopositive neurons expressed CCR7-10, except CR-immunopositive cells in which only 10 to 12% expressed CCR8. During and after pilocarpine-induced status epilepticus, progressive changes of each of CCR7, CCR8, CCR9 and CCR10 proteins occurred in different patterns at various time points. Sensitive real-time PCR showed similar change patterns at mRNA level. At the chronic stage, i.e. at 2 months after pilocarpine-induced status epilepticus, significant reduction of CCR7-10 expression in CB-, CR- and PV-immunpositive interneurons may suggest the phenotype change of surviving interneurons. Double labelling of CCR7, CCR8 and CCR9 with glial fibrillary acidic protein (GFAP) at the chronic stage may suggest an induced expression in reactive astrocytes. The present study may, therefore, for the first time, provide evidence that CCR7-10 may be involved in normal hippocampal activity. The demonstration of the progressive changes of CCR7-10 during and after status epilepticus may open a new area to reveal the mechanism of neuronal loss after status epilepticus and of epileptogenesis.

Animals↗
PubMed2007

Mesenteric desmoid tumors in Singapore familial adenomatous polyposis patients: clinical course and genetic profile in a predominantly Chinese population.

PURPOSE: This study examined the mutational profile of the adenomatous polyposis coli gene in relation to the development of desmoid tumors in familial adenomatous polyposis patients from a predominantly Chinese population. METHODS: This is a retrospective review of all patients with familial adenomatous polyposis coli from the Singapore Polyposis Registry. Identification of specific adenomatous polyposis coli gene mutation was performed and clinical course of associated desmoid disease obtained from case records and a computerized database. RESULTS: Two hundred five patients from 75 families afflicted with familial adenomatous polyposis coli were reviewed, with gene mutations identified in 107 patients. Of these, 23 (11.2 percent) developed desmoids. The male-to-female ratio was 1:1.3 and the ethnic distribution was Chinese (n=17) and Malay (n=6). Of the 92 patients with mutations 5' to codon 1444, 11 patients (12 percent) developed desmoids compared with 6 of 15 (40 percent) patients with adenomatous polyposis coli gene mutations 3' to codon 1444 (P<0.01). The clinical course of desmoid tumors can be divided into stable (n=11), variable (n=3), progressive (n=6), and aggressive growth (n=3). Only 3 (13 percent) patients with aggressive tumor growth required chemotherapy. There was no correlation between the site of mutation and the clinical progression of the desmoids. Seventy-four percent of these desmoids (17/23) developed at a mean interval of 2.98 years after restorative proctocolectomy, while only 30 percent (7/23) were diagnosed preoperatively or discovered during the initial surgery. The most common complications related to the mesenteric desmoids were intestinal obstruction (21.7 percent), ureteric obstruction (17.4 percent), and encasement of superior mesenteric vessels (13 percent). CONCLUSION: The clinical course of desmoids in an individual familial adenomatous polyposis patient remains unpredictable and no reliable genetic marker is available for prognostication in desmoid disease.

Adenomatous Polyposis Coli↗
PubMed2006

Parathyroid hormone activates phosphoinositide 3-kinase-Akt-Bad cascade in osteoblast-like cells.

To understand the molecular basis underlying the anabolic action of parathyroid hormone (PTH) on bone, the anti-apoptotic action of PTH on osteoblast-like cells was investigated. Since Akt is a key protein kinase for cell survival, we focused on a possible involvement of Akt in the anti-apoptotic action of PTH. Human osteoblast-like MG-63 cells cultured without serum were treated with PTH. Western blot analysis revealed that PTH rapidly phosphorylated Akt and induced its nuclear translocation. The phosphorylation of pro-apoptotic protein Bad was also increased by PTH, leading to its inactivation. The PTH-dependent activation of Akt was also detected in other osteoblastic cell lines, SaOS-2 and ROS 17/2.8. The pretreatment of MG-63 cells with either one of inhibitors for phosphoinositide 3-kinase (PI3K), wortmannin or LY294002 prevented Akt and Bad phosphorylation. Furthermore, co-immunoprecipitation analysis revealed that PTH receptor (PTH-1R) directly interacted with p85, a regulatory subunit of PI3K, in a PTH-dependent manner. Serum withdrawal induced the apoptosis of MG-63 cells, and PTH prevented the apoptosis, which was inhibited by PI3K inhibitors. These results demonstrate the presence of a novel PTH/PTH receptor signaling cascade consisting of PTH-1R, PI3K, Akt and Bad and that this cascade can work as an anti-apoptotic signaling pathway in osteoblast-like cells.

Androstadienes↗
PubMed2006

Singapore familial adenomatous polyposis (FAP) patients with classical adenomatous polyposis but undetectable APC mutations have accelerated cancer progression.

OBJECTIVES: Germline mutation in adenomatous polyposis coli (APC) is detected in up to 80% of familial adenomatous polyposis (FAP) patients worldwide. In this study, we evaluated clinical features and APC mutations of Singapore FAP patients and contrasted genotype-phenotype correlation with Caucasians from other regions of the world and between FAP patients with and without detectable APC mutations. METHODS: We screened 242 members from 57 unrelated FAP families using a combination of cDNA protein truncation test, multiplex ligation-dependent probe amplification, and differential expression techniques. RESULTS: APC germline mutations were detected in 50 families. In contrast to Caucasians, fundic gland polyposis in Singapore patients was associated with APC mutations throughout the coding region and osteomas were also not confined to codon 767-1573. There was also no FAP-associated hepatoblastoma or medullablastoma. APC mutation-negative patients from four families with mixed (adenomatous/hyperplastic/atypical juvenile) polyps were subsequently reclassified as hereditary mixed polyposis syndrome (HMPS) patients. APC mutation-negative patients with classical adenomatous polyposis were negative for MYH, beta-catenin, and Axin 1 mutations. These patients had a significantly older age at diagnosis (P < 0.001) and more colorectal cancers (P= 0.017) than patients with APC mutations. CONCLUSIONS: We achieved a 94% (50/53) APC mutation detection rate via a combination of techniques, suggesting that the current detection rate is probably not exhaustive. Singapore patients have some features similar to and other features distinct from Caucasians. Furthermore, APC mutation-negative patients have accelerated cancer progression that merits closer surveillance.

Adenomatous Polyposis Coli↗
PubMed2006

Plasma serotonin levels in young violent offenders: Aggressive responding and personality correlates.

70 young male violent offenders and 30 normal controls in Hunan, China were interviewed and assessed by the Minnesota Multiphasic Personality Inventory (MMPI), Point Subtraction Aggression Paradigm (PSAP) and plasma serotonin (5-HT) level. Compared to the normal controls, the violent offenders had significantly higher plasma 5-HT levels; higher scores on the MMPI subscale Pd (P < 0.01), Pa (P < 0.05); and higher PSAP-B responding and lower PSAP-C responding (P < 0.05). There was a positive correlation between the MMPI Pd score and the PSAP B response, but no significant correlation was found between Pd score and plasma 5-HT level, or between PSAP B response and plasma 5-HT level. Our data suggest that the young violent offenders are more aggressive than the normal control. But this study did not demonstrate that the plasma 5-HT level had a correlation with the PSAP aggressive response. The relationship between the aggressiveness and impulsivity in the violent behavior needs further study.

Adolescent↗
PubMed2006

Thyroid hormone mediated changes in gene expression can be initiated by cytosolic action of the thyroid hormone receptor beta through the phosphatidylinositol 3-kinase pathway.

Thyroid hormone (TH) action is mediated principally through binding of the hormone ligand, 3,3,5-triiodothyronine (T3), to TH receptors (TRs). This hormone-receptor interaction recruits other proteins to form complexes that regulate gene expression by binding to DNA sequences in the promoter of target genes. We recently described an extranuclear mechanism of TH action that consists of the association of TH-liganded TRbeta with p85alpha [regulatory subunit of phosphatidylinositol 3-kinase (PI3K)] in the cytosol and subsequent activation of the PI3K, generating phosphatidylinositol 3,4,5-triphosphate [PtdIns(3,4,5)P3]. This initiates the activation of a signaling cascade by phosphorylation of Akt, mammalian target of rapamycin (mTOR) and its substrate p70(S6K), leading to the stimulation of ZAKI-4alpha synthesis, a calcineurin inhibitor. Furthermore, we found that this same mechanism leads to induction of the transcription factor hypoxia-inducible factor (HIF-1alpha), and its target genes, glucose transporter (GLUT)1, platelet-type phosphofructokinase (PFKP), and monocarboxylate transporter (MCT) 4. These genes are of special interest, because their products have important roles in cellular glucose metabolism, from glucose uptake (GLUT1) to glycolysis (PFKP) and lactate export (MCT4). These results demonstrate that the TH-TRbeta complex can exert a non-genomic action in the cytosol leading to changes in gene expression by direct (HIF-1alpha) and indirect (ZAKI-4alpha, GLUT1, PFKP) means.

Journal Article↗
PubMed2006

DHCR24-knockout embryonic fibroblasts are susceptible to serum withdrawal-induced apoptosis because of dysfunction of caveolae and insulin-Akt-Bad signaling.

The DHCR24 gene encodes an enzyme catalyzing the last step of cholesterol biosynthesis, the conversion of desmosterol to cholesterol. To elucidate the physiological significance of cholesterol biosynthesis in mammalian cells, we investigated proliferation of mouse embryonic fibroblasts (MEFs) prepared from DHCR24(-/-) mice. Both DHCR24(-/-) and wild-type MEFs proliferated in the presence of serum in culture media. However, the inhibition of external cholesterol supply by serum withdrawal induced apoptosis of DHCR24(-/-) MEFs, which was associated with a marked decrease in the intracellular and plasma membrane cholesterol levels, Akt inactivation, and Bad dephosphorylation. Insulin is an antiapoptotic factor capable of stimulating the Akt-Bad cascade, and its receptor (IR) is enriched in caveolae, cholesterol-rich microdomains of plasma membrane. We thus analyzed the association of IR and caveolae in the cholesterol-depleted MEFs. Subcellular fractionation and immunocytochemical analyses revealed that the IR and caveolin-1 contents were markedly reduced in the caveolae fraction of the MEFs, suggesting the disruption of caveolae, and that large amounts of IR were present apart from caveolin-1 on plasma membrane, indicating the uncoupling of IR with caveolae. Consistent with these findings, insulin-dependent phosphorylations of insulin receptor substrate-1, Akt, and Bad were impaired in the cholesterol-depleted MEFs. However, this impairment was partial because treatment of the MEFs with insulin restored Akt activation and prevented apoptosis. Cholesterol supply also prevented apoptosis. These results demonstrate that the cellular cholesterol biosynthesis is critical for the activation and maintenance of the Akt-Bad cell survival cascade in response to growth factors such as insulin.

Animals↗
PubMed2006

Fenofibrate activates AMPK and increases eNOS phosphorylation in HUVEC.

Fenofibrate improves endothelial function by lipid-lowering and anti-inflammatory effects. Additionally, fenofibrate has been demonstrated to upregulate endothelial nitric oxide synthase (eNOS). AMP-activated protein kinase (AMPK) has been reported to phosphorylate eNOS at Ser-1177 and stimulate vascular endothelium-derived nitric oxide (NO) production. We report here that fenofibrate activates AMPK and increases eNOS phosphorylation and NO production in human umbilical vein endothelial cells (HUVEC). Incubation of HUVEC with fenofibrate increased the phosphorylation of AMPK and acetyl-CoA carboxylase. Fenofibrate simultaneously increased eNOS phosphorylation and NO production. Inhibitors of protein kinase A and phosphatidylinositol 3-kinase failed to suppress the fenofibrate-induced eNOS phosphorylation. Neither bezafibrate nor WY-14643 activated AMPK in HUVEC. Furthermore, fenofibrate activated AMPK without requiring any transcriptional activities. These results indicate that fenofibrate stimulates eNOS phosphorylation and NO production through AMPK activation, which is suggested to be a novel characteristic of this agonist and unrelated to its effects on peroxisome proliferator-activated receptor alpha.

AMP-Activated Protein Kinases↗
PubMed2005

Glutathionylation of two cysteine residues in paired domain regulates DNA binding activity of Pax-8.

We reported that the first two cysteine residues out of three present in paired domain (PD), a DNA-binding domain, are responsible for redox regulation of Pax-8 DNA binding activity. We show that glutathionylation of these cysteines has a regulatory role in PD binding. Wild-type PD and its mutants with substitution of cysteine to serine were synthesized and named CCC, CSS, SCS, SSC, and SSS according to the positions of substituted cysteines. They were incubated in a buffer containing various ratios of GSH/GSSG and subjected to gel shift assay. Binding of CCC, CSS, and SCS was impaired with decreasing GSH/GSSG ratio, whereas that of SSC and SSS was not affected. Because [3H]glutathione was incorporated into CCC, CSS, and SCS, but not into SSC and SSS, the binding impairment was ascribed to glutathionylation of the redox-reactive cysteines. This oxidative inactivation of PD binding was reversed by a reductant dithiothreitol and by redox factor (Ref)-1 in vitro. To explore the glutathionylation in cells, Chinese hamster ovary cells overexpressing CSS and SCS were labeled with [35S]cysteine in the presence of cycloheximide. Immunoprecipitation with an antibody against PD revealed that treatment of the cells with an oxidant diamide induced the 35S incorporation into both mutants, suggesting the PD glutathionylation in cells. Since the two cysteine residues in PD are conserved in all Pax members, this novel posttranslational modification of PD would provide a new insight into molecular basis for modulation of Pax function.

Animals↗
PubMed2005

Requirement of thyrotropin-dependent complex formation of protein kinase A catalytic subunit with inhibitor of {kappa}B proteins for activation of p65 nuclear factor-{kappa}B by tumor necrosis factor-{alpha}.

We previously demonstrated that TNF-alpha-dependent activation of p65 nuclear factor kappaB in rat thyroid FRTL-5 cells requires TSH. In the present study, we investigated the mechanism of this TSH action. Western blot analysis revealed that, in both the presence and absence of TSH, degradation of a cytosolic kappaB inhibitor (IkappaBalpha) occurred in response to TNF-alpha, resulting in nuclear translocation of p65 in both conditions. However, no DNA binding of p65 was detected in the absence of TSH, suggesting that posttranslational modification of p65 by TSH is required for its binding. Treatment of the cells cultured in the presence of TSH with a protein kinase A (PKA) inhibitor, H89, markedly reduced p65 binding and its transcriptional activity. However, transient block of TSH/cAMP-dependent activation of PKA catalytic subunit (PKAc) by adenylate cyclase inhibitor, SQ22536, had no effects on the p65 activation. Interestingly, it was found that PKAc formed a complex with IkappaBalpha and beta only in the presence of TSH, and this PKAc could be activated by TNF-alpha. TNF-alpha-dependent p65 activation was temporally associated with PKAc/IkappaBalpha complex formation. More than 3 h exposure of TSH was required for the complex formation and p65 activation. These results demonstrate that TSH induces the formation of PKAc/IkappaB complex in FRTL-5 cells and that this PKAc bound with IkappaB plays a critical role in TNF-alpha-dependent activation of p65.

Active Transport, Cell Nucleus↗
PubMed2005

Effect of beta radiation on TGF-beta1 and bFGF expression in hyperplastic prostatic tissues.

AIM: To investigate the transforming growth factor beta1 (TGF-beta1) and basic fibroblast growth factor (bFGF) expressions in benign prostatic hyperplasia (BPH) and the effect of beta-radiation. METHODS: TGF-beta1 and bFGF expression was studied by means of an immunohistochemical method in nine normal prostatic (NP) tissues, 15 hyperplastic prostatic tissues and 35 hyperplastic prostatic tissues treated with 90Sr/90Y. RESULTS: The TGF-beta1 expression in the epithelium and stroma of normal prostatic tissues was 68.2 % +/- 10.5 % and 29.7 % +/- 4.6 %, respectively, while it was 64.8 % +/- 9.3 % and 28.6 % +/- 4.1 %, respectively, in hyperplastic prostatic tissues. Compared with the controls, TGF-beta1 expression in the epithelia and stroma of BPH treated with 90Sr/90Y increased significantly (P <0.01). The bFGF expression in epithelia and stroma of normal prostatic tissues was 17.4 % +/- 3.7 % and 42.5 % +/- 6.8 %, respectively, and was 46.3 % +/- 8.2 % and 73.2 % +/- 12.1 %, respectively, in hyperplastic prostatic tissues. Compared with the controls, expressions of bFGF in the epithelia and stroma of BPH treated with a 90Sr/90Y prostatic hyperplasia applicator decreased significantly (P <0.01). CONCLUSION: Exposure of beta-rays had noticeable effects on BPH tissues, enhancing TGF-beta1 expression and inhibiting bFGF expression.

Aged↗
PubMed2005

[Haplotype and linkage analysis in Chinese hereditary mixed polyposis syndrome].

OBJECTIVE: To investigate if hereditary mixed polyposis syndrome (HMPS) locus of two Singapore Chinese HMPS families is identical with the Ashkenazi families. METHODS: Genomic DNA was extracted, multiplex polymerase chain reaction (PCR) was used to amplify 4 microsatellite markers D15S1010, D15S1007, ACTC and D15S118 in 31 individuals from two families. The HMPS locus cosecretion of the markers on 15q13 over a region of 2.8 cM was confirmed by Haplotype and linkage analysis. RESULTS: The disease of haplotype identified in one pedigree was not co-segregated with an affected individual while no definitive disease haplotype could be assigned for the second pedigree. The maximum two-point and multi-point LOD scores at ACTC for the two Chinese families are 0.20 (theta = 0.3) and -5.0 respectively. CONCLUSIONS: Haplotype and linkage analysis indicate that the Ashkenazi haplotypes is not associated with HMPS in Singapore Chinese families, which suggests genetic heterogeneity.

Adenomatous Polyposis Coli↗
PubMed2004

Thyroid hormone induces rapid activation of Akt/protein kinase B-mammalian target of rapamycin-p70S6K cascade through phosphatidylinositol 3-kinase in human fibroblasts.

We have demonstrated that T3 increases the expression of ZAKI-4alpha, an endogenous calcineurin inhibitor. In this study we characterized a T3-dependent signaling cascade leading to ZAKI-4alpha expression in human skin fibroblasts. We found that T3-dependent increase in ZAKI-4alpha was greatly attenuated by rapamycin, a specific inhibitor of a protein kinase, mammalian target of rapamycin (mTOR), suggesting the requirement of mTOR activation by T3. Indeed, T3 activated mTOR rapidly through S2448 phosphorylation, leading to the phosphorylation of p70(S6K), a substrate of mTOR. This mTOR activation is mediated through phosphatidylinositol 3-kinase (PI3K)-Akt/protein kinase B (PKB) signaling cascade because T3 induced Akt/PKB phosphorylation more rapidly than that of mTOR, and these T3-dependent phosphorylations were blocked by both PI3K inhibitors and by expression of a dominant negative PI3K (Deltap85alpha). Furthermore, the association between thyroid hormone receptor beta1 (TRbeta1) and PI3K-regulatory subunit p85alpha, and the inhibition of T3-induced PI3K activation and mTOR phosphorylation by a dominant negative TR (G345R) demonstrated the involvement of TR in this T3 action. The liganded TR induces the activation of PI3K and Akt/PKB, leading to the nuclear translocation of the latter, which subsequently phosphorylates nuclear mTOR. The rapid activation of PI3K-Akt/PKB-mTOR-p70(S6K) cascade by T3 provides a new molecular mechanism for thyroid hormone action.

Active Transport, Cell Nucleus↗
PubMed2004

Inhibitory effects of cyclosporin A on calcium mobilization-dependent interleukin-8 expression and invasive potential of human glioblastoma U251MG cells.

Interleukin (IL)-8 produced from glioblastoma is suggested to contribute to its own proliferation and progression. Since various external stimuli have been shown to increase intracellular Ca(2+) in glioma cells, we investigated Ca(2+) mobilization-dependent IL-8 expression and effect of cyclosporin A (CsA), an inhibitor of calcineurin (Cn), on the expression and invasive potential of human glioblastoma U251MG cells. Combined treatment with Ca(2+)-ionophore and phorbol-myristate-acetate (A23187/PMA) increased IL-8 mRNA and protein levels. This increase was suppressed by CsA and by another Cn inhibitor FK506. Luciferase reporter gene assay and electrophoretic mobility shift assay revealed that activation of p65-containing nuclear factor-kappaB was essential for A23187/PMA-dependent activation of IL-8 promoter. CsA suppressed the promoter activity by attenuating IkappaB-alpha degradation. U251MG cells expressed IL-8 receptors CXCR-1 and -2, and Matrigel invasion assay revealed that CsA attenuated A23187/PMA-dependent stimulation of invasive potential, probably by inhibiting IL-8 production. In addition, IL-8-dependent proliferation was also suppressed by CsA. Taken together, these results demonstrate the novel inhibitory effects of CsA on glioblastoma cell functions, suggesting CsA as a potential therapeutic adjuvant for glioma treatment.

Calcimycin↗
PubMed2004

Design of a novel hydrogel-based intelligent system for controlled drug release.

The present work focused on the design of an assembled drug delivery system (DDS) to provide multifunctions, such as drug protection, self-regulated oscillatory release, and targeted uni-directional delivery by a bilayered self-folding gate and simple surface mucoadhesion. In this device, a pH-sensitive hydrogel together with a poly(hydroxyethyl methacrylate) (HEMA) barrier was used as a gate to control drug release. In addition, poly(HEMA) coated with poly(ethylene oxide)/poly(propylene oxide)/poly(ethylene oxide) (PEO-PPO-PEO) surfactant was utilized to enhance mucoadhesion on the device surface. The release profiles of two model drugs, acid orange 8 (AO8) and bovine serum albumin (BSA) were studied in this assembled system, which compared with the conventional drug-entrapped carriers and enteric-coating systems. Furthermore, targeted uni-directional release was demonstrated in a side-by-side diffusion cell. In conclusion, for such an assembled device, the poly(HEMA) layer not only affects the folding direction but also serves as a barrier to protect the model drugs. The release time can be controlled by the thickness of the bilayered gate and the drug reservoir. Due to the reversible swelling behavior of poly(methyacrylic acid-g-ethylene glycol) (p(MAA-g-EG)) gels, the bilayered gate can sense the environmental pH change and achieve an oscillatory release pattern. Moreover, the local targeting and uni-directional release have been successfully demonstrated in vitro.

Coloring Agents↗
PubMed2004

A packaging technique for polymer microfluidic platforms.

A new technique, resin-gas injection, has been developed for bonding and surface modification of polymer microfluidic devices. This method can easily bond biochips with complex flow patterns. A cascade micromixer and a multichannel DNA sequencing chip were demonstrated experimentally. By adding surface modification agents, the interfacial free energy of the substrate with water can be controlled. Local modification of the channel surface can also be achieved through sequential resin-gas injection in conjunction with a masking technique. For application, this technique is used to form a layer of dry monolithic stationary hydrogel on the walls of a microchannel, serving as a sieving material for electrophoresis separation of DNA fragments. The reagent loading and the electrophoresis separation efficiency of this technique were compared experimentally with the conventional linear polymer solution method used in the microchannel-based DNA sequencing process. It is found that our method has the advantages of more user-friendly operation, easier and faster sample loading, but slightly less separation efficiency.

DNA↗
PubMed2004

Resistance to ischemic acute renal failure in the Brown Norway rat: a new model to study cytoprotection.

BACKGROUND: An in vivo model of intrinsic resistance to ischemia could be invaluable to define how specific pathways to injury or putative protectors from injury affect the severity of acute renal failure (ARF). The purpose of this study was to determine whether separate rat strains had differential sensitivity to renal ischemia, characterize the extent of protection, and begin to define differences in gene expression that might impact on the severity of ARF. METHODS: The sensitivity to 45 minutes of renal ischemia in Sprague-Dawley rat (SD) was compared with 2 lines of Brown-Norway rats (BN/Mcw, BN/Hsd). Constitutive and inducible stress protein expression was compared between strains. RESULTS: At 24 hours' reperfusion, SD rats had higher creatinine (3.4 mg/dL), elevated Na and water excretion, and proximal tubule necrosis. Both strains of BN rats were resistant to loss of renal function (Scr = 0.9 mg/dL at 24 hours' reflow) and had preserved renal morphology. BN rats had no redistribution of Na,K-ATPase into detergent-soluble cortical extracts found early (15 minutes) after ischemia in SD rats. Hsc73 expression did not differ between strains and was not induced by ischemia. Compared with SD, induction of Hsp25 and 72 by renal ischemia was blunted in both BN strains. Constitutive Hsp25 was higher in both BN-Mcw and BN-Hsd compared with SD rat kidney. Constitutive Hsp72 was significantly higher only in BN-Mcw kidneys. Immunohistochemistry showed baseline Hsp72 and 25 expression was increased in proximal tubules of BN-Mcw versus SD. CONCLUSION: BN rat kidney is resistant to ischemic injury and provides a new model for studying cytoprotective mechanisms. Initial study of strain-specific gene expression suggests particular stress proteins are among the potential mechanisms contributing to protection against ARF.

Acute Kidney Injury↗