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Biomedical subjects

Alberto Ortiz

Publications and source records attributed to Alberto Ortiz.

At least 19 recordsLinked to original sources
PubMed2006

Fn14 is upregulated in cytokine-stimulated vascular smooth muscle cells and is expressed in human carotid atherosclerotic plaques: modulation by atorvastatin.

BACKGROUND AND PURPOSE: Interaction between different members of the tumor necrosis factor superfamily and their receptors elicits diverse biologic actions that are implicated in the pathogenesis of atherosclerosis. We have analyzed the expression of Fn14 and its ligand TWEAK in carotid atherosclerotic plaques and its potential modulation by atorvastatin in vivo. Furthermore, we have studied whether proinflammatory cytokines regulate Fn14 expression in human aortic smooth muscle cells (hASMCs) in culture as well as the potential regulation by atorvastatin treatment. METHODS: Fn14 and TWEAK expression was analyzed in human carotid atherosclerotic plaques. Furthermore, Fn14 expression was studied in hASMCs in culture. RESULTS: Fn14 and TWEAK are expressed in macrophages and smooth muscle cells in carotid atherosclerotic plaques. Proinflammatory cytokines (interleukin-1beta and interferon-gamma) upregulate Fn14 expression in hASMCs. This effect was prevented by atorvastatin treatment and reversed by mevalonate and geranylgeranyl pyrophosphate. Geranylgeranyl transferase inhibitor, toxin B (Rac and Rho inhibitor), C3 exoenzyme (Rho inhibitor), and Y-27632 (Rho kinase inhibitor) also decreased Fn14 expression, implicating the Rho/Rho kinase pathway in the regulation of Fn14 expression. Finally, atorvastatin treatment reduced Fn14 expression in vivo. CONCLUSIONS: TWEAK and Fn14 are expressed in atherosclerotic plaques and could be novel mediators of atherosclerosis. Atorvastatin diminishes Fn14 expression in vitro and in vivo providing novel information of the beneficial properties of statins.

Aged↗
PubMed2006

Peritoneal defence--lessons learned which apply to diabetes complications.

Peritoneal dialysis (PD) and diabetes mellitus share the high glucose concentration in the cell microenvironment. This has led to the suggestion that they may also share pathogenic pathways of cell and tissue injury. Hypotheses have been formulated on the pathogenesis of peritoneal injury in the course of PD that take into account knowledge of the mechanisms of tissue injury in diabetes patients. More recently, research on the pathways of PD complications has uncovered potentially novel mediators of diabetes complications. Accelerated leucocyte apoptosis has been identified as a cause of impaired peritoneal antibacterial defence in PD, which may lead to new therapeutic interventions. In this regard, interference with leucocyte apoptosis by the use of caspase inhibitors may accelerate the clearance of bacteria such as Staphylococcus aureus, which cause significant morbidity in both PD and diabetes patients. Evidence suggests that glucose degradation products in PD solutions accelerate leucocyte apoptosis. In particular, 3,4-di-deoxyglucosone-3-ene (3,4-DGE) accounted for most, if not all, the cytotoxicity of PD fluids against neutrophils and lymphocytes. Interestingly, 3,4-DGE also induces apoptosis in cells, such as renal epithelium, from organs that are targets of diabetes complications. This raises the possibility that apoptosis induction by glucose metabolites that are the key participants in PD complications may underlie the pathogenesis of some features of diabetic tissue injury.

Animals↗
PubMed2006

Impact of end-stage renal disease care in planned dialysis start and type of renal replacement therapy--a Spanish multicentre experience.

BACKGROUND: Timely referral, preparation and initiation of dialysis remain problematic issues. The purpose of this study is to analyse the effect of chronic renal disease care and education on the mode of dialysis start (planned vs non-planned) and on the modality of renal replacement therapy (RRT). METHODS: A total of 1504 patients from 35 hospitals started RRT in 2003. Out-patient, scheduled initiation of dialysis with a permanent vascular or peritoneal access was considered planned. RESULTS: About 46% of the patients started non-planned dialysis. Of all the patients, 75% had > or =3 months of nephrological follow-up, but nearly half were never educated on dialysis options. Haemodialysis (HD) occurred in 82% and peritoneal dialysis (PD) in 18%. Planned starts were associated (all P < 0.001) with many factors: younger age, longer renal and pre-dialysis follow-up, more education on RRT and general care, more medical visits, more PD (27 vs 8%), more follow-up by specific end-stage renal disease (ESRD) units, more permanent access and better biochemical status at the start of dialysis. Some global differences were found between patients: planned vs non-planned with > or =3 months of follow-up, vs non-planned <3 months follow-up or acute non-planned and <3 months of follow-up or acute patients. HD occurred in a similar rate (92%) in patients with non-planned start, no previous follow-up or who were never educated in dialysis modality options. CONCLUSION: Although a high prevalence of nephrologic care and follow-up was provided among incident patients in dialysis, nearly half the patients did not have a planned dialysis start nor dialysis modality education. Planned start was associated with better analytical and multidisciplinary status. PD was more prevalent in planned starts and when education was given. Specific ESRD units were more likely to provide an optimal care.

Diabetes Mellitus↗
PubMed2006

[Assessment of the invasiveness of rapidly-growing nonpigmented mycobacteria with the fibroblast microcolony assay].

OBJECTIVE: The invasive capacity of rapidly-growing nonpigmented mycobacteria strains was evaluated by means of a fibroblast microcolony assay and related to the colony phenotype on Middlebrook 7H11 and to the clinical significance of the isolates. METHODS: Twenty-nine strains [Mycobacterium chelonae (8), M. fortuitum (6), M. peregrinum (5), M. abscessus (5), M. mucogenicum (4) and M. septicum (1)], proceeding from a bacterial collection and clinical isolates, were evaluated. The smooth or rough phenotype of the colonies was assessed in Middlebrook 7H11 medium. Intracellular invasiveness was determined by the fibroblast-microcolony assay described by Shepard. Quantitative culture characteristics were compared with Student's t-test, and qualitative characteristics with Fisher's exact test. RESULTS: No significant differences were found between colonies with different phenotypes or strains having a different clinical significance, except for two strains of Mycobacterium chelonae isolated from cases of catheter-related bacteremia, which showed elongated microcolonies. M. fortuitum and M. peregrinum strains showed larger microcolonies than M. chelonae, M. abscessus and M. mucogenicum, and displayed a fluffy appearance, while the latter two strains showed rounded colonies. CONCLUSION: Very few strains of mycobacteria had invasive capacity and the majority of strains isolated from human infections do not show this characteristic; hence this trait is not essential for mycobacteria to cause infection in humans.

Bacteriological Techniques↗
PubMed2006

3,4-DGE is important for side effects in peritoneal dialysis what about its role in diabetes.

Breakdown of glucose under physiological conditions gives rise to glucose degradation products (GDPs). GDPs are also formed during heat sterilization of glucose-containing peritoneal dialysis fluids (PD-fluids). In PD-fluids GDPs have been shown in many different in vitro assays to be responsible for adverse effects such as growth inhibition, and impaired leukocyte function and impaired wound healing of peritoneal mesothelial cells. They have been linked to changes in the peritoneal membrane as well as to the decline in residual renal function of PD-patients. In diabetes one of the GDPs, 3-deoxyglucosone (3-DG), has been proposed as responsible for side-effects rather the glucose itself. 3,4-dideoxyglucosone-3-ene (3,4-DGE) was recently identified as the most bio-reactive GDP in PD-fluids. It exists in equilibrium with a pool of precursors, consisting of 3-DG but also of other hitherto unidentified GDPs. In PD-fluids the concentration of GDPs in this pool is 10-20 times as high as that of 3,4-DGE. In vitro 3,4-DGE induces caspase-dependent apoptosis of neutrophils and peripheral blood mononuclear cells. Such induction may explain immunosuppressive properties of 3,4-DGE and contribute to an impaired peritoneal antibacterial defense. 3,4-DGE also induces renal cell apoptosis. This may explain the better preservation of residual renal function in PD patients not exposed to GDPs. The concentration of 3-DG increases with worsening glycemic control and has been implicated in the genesis of diabetic microangiopathy. As 3,4-DGE is much more bio-reactive than 3-DG and as it may be easily recruited from the pool, it seems probable that 3,4-DGE is the molecule involved in the diabetic lesions rather than 3-DG itself. Thus, 3,4-DGE might contribute to diabetic nephropathy and to the impaired antibacterial defenses in diabetics. Unraveling of the pool dynamics of the GDPs and the molecular mechanisms of GDP-mediated cell injury may provide new therapeutic insights in PD and diabetes.

Apoptosis↗
PubMed2005

Erythromelalgia with subsequent digital necrosis, glomerulonephritis, and antiphospholipid antibodies.

Erythromelalgia is a condition of extremities characterized by redness, increased temperature, and burning pain. We describe the first reported case of erythromelalgia in a young woman with digital necrosis and mesangial nephritis associated with antiphospholipid antibodies. The symptoms and necrosis completely resolved with treatment with corticosteroids. We discuss the differential diagnosis of this entity and highlight the importance of a follow up of these patients, because erythromelalgia may precede a myeloproliferative disorder or systemic lupus erythematosus by months or years.

Adolescent↗
PubMed2005

3,4-di-deoxyglucosone-3-ene promotes leukocyte apoptosis.

BACKGROUND: Heat-sterilized, single-chambered, glucose-containing peritoneal dialysis solutions promote neutrophil apoptosis and impair the peritoneal antibacterial response. It has been proposed that glucose degradation products may be responsible for this effect. However, the precise contribution of individual glucose degradation products had not been addressed. METHODS: The effect of individual glucose degradation products on apoptosis in cultured human neutrophils and peripheral blood mononuclear cells was studied. RESULTS: Peritoneal dialysis solutions with a high content of both glucose and glucose degradation products accelerated neutrophil and mononuclear cell apoptosis. Among the different glucose degradation products, 3,4-di-deoxyglucosone-3-ene (3,4-DGE) accelerated apoptosis in neutrophils and peripheral blood mononuclear cells at concentrations (25 micromol/L) in the range found in heat-sterilized, single-chambered, 4.25% glucose peritoneal dialysis fluids. Apoptosis induced by 3,4-DGE was caspase-dependent and could be prevented by the broad-spectrum caspase inhibitor benzyloxycarbonyl-Val-Ala-DL-Asp-fluoromethylketone (zVAD-fmk). By contrast, no cytotoxicity was observed following the addition of methylglyoxal, acetaldehyde, formaldehyde, or 3-deoxyglucosone at concentrations found in peritoneal dialysis solutions. CONCLUSION: 3,4-DGE appears to be the main proapoptotic factor in high glucose peritoneal dialysis solutions. 3,4-DGE may impair peritoneal defenses by accelerating leukocyte apoptosis.

Apoptosis↗
PubMed2005

3,4-Dideoxyglucosone-3-ene induces apoptosis in renal tubular epithelial cells.

Diabetes complications are caused by hyperglycemia. Hyperglycemia results in increased concentrations of glucose degradation products. The study of peritoneal dialysis solution biocompatibility has highlighted the adverse effects of glucose degradation products. Recently, 3,4-dideoxyglucosone-3-ene (3,4-DGE) has been identified as the most toxic glucose degradation product in peritoneal dialysis fluids. Its role in renal pathophysiology has not been addressed. 3,4-DGE induces apoptosis in murine renal tubular epithelial cells in a dose- and time-dependent manner. Peak apoptosis is observed after 72 h of culture. The lethal concentration range is 25-50 micromol/l. 3,4-DGE results in Bax oligomerization, release of cytochrome c from mitochondria, activation of caspases-9 and -3, and Bid proteolysis. Apoptosis induced by 3,4-DGE is caspase dependent and could be prevented by the broad-spectrum caspase inhibitor zVAD-fmk (Z-Val-Ala-DL-Asp-fluoromethylketone) and by specific inhibitors of caspases-2, -8, and -9. However, caspase inhibition did not prevent eventual cell death. In contrast, antagonism of Bax by a Ku-70-derived peptide or antisense oligonucleotides prevented both apoptosis and cell death. In conclusion, 3,4-DGE promotes apoptosis of cultured renal parenchymal cells by a Bax- and caspase-dependent mechanism. A role for 3,4-DGE in diabetes complications in the kidney and in the modulation of residual renal function in peritoneal dialysis should be further explored.

Animals↗
PubMed2005

Tubular cell apoptosis and cidofovir-induced acute renal failure.

Cidofovir is an antiviral drug with activity against a wide array of DNA viruses including poxvirus. The therapeutic use of cidofovir is marred by a dose-limiting side effect, nephrotoxicity, leading to proximal tubular cell injury and acute renal failure. Treatment with cidofovir requires the routine use of prophylactic measures. A correct knowledge of the cellular and molecular mechanisms of cidofovir toxicity may lead to the development of alternative prophylactic strategies. We recently cared for a patient with irreversible acute renal failure due to cidofovir. Renal biopsy showed tubular cell apoptosis. Cidofovir induced apoptosis in primary cultures of human proximal tubular cells in a temporal (peak apoptosis at 7 days) and concentration (10-40 microg/ml) pattern consistent with that of clinical toxicity. Apoptosis was identified by the presence of hypodiploid cells, by the exposure of annexin V binding sites and by morphological features and was associated with the appearance of active caspase-3 fragments. Cell death was specific as it was also present in a human proximal tubular epithelial cell line (HK-2), but not in a human kidney fibroblast cell line, and was prevented by probenecid. An inhibitor of caspase-3 (DEVD) prevented cidofovir apoptosis. The survival factors present in serum, insulin-like growth factor-1 and hepatocyte growth factor, were also protective. The present data suggest that apoptosis induction is a mechanism contributing to cidofovir nephrotoxicity. The prophylactic administration of factors with survival activity for tubular epithelium should be further explored in cidofovir renal injury.

Acute Kidney Injury↗
PubMed2004

Persistent proteinuria up-regulates angiotensin II type 2 receptor and induces apoptosis in proximal tubular cells.

Apoptosis is implicated in the progressive cell loss and fibrosis both at glomerular and tubulointerstitial level. In this study, we examined the potential mechanisms by which persistent proteinuria (protein-overload model) could induce apoptosis. After uninephrectomy (UNX), Wistar rats received daily injections of 0.5 g of bovine serum albumin (BSA)/100 g body weight or saline. Both at day 8 and day 28, rats receiving BSA had proteinuria and renal lesions characterized by tubular atrophy and/or dilation and mononuclear cell infiltration. In relation to control-UNX rats, renal cortex of nephritic rats showed an increment in AT2 mRNA (reverse transcriptase-polymerase chain reaction) and protein (Western blot) expression. In both groups, AT2 receptor immunostaining was mainly localized in proximal tubular cells. Rats with persistent proteinuria showed a significantly increased number of terminal dUTP nick-end labeling positive apoptotic cells compared with UNX-controls, both in glomeruli and tubulointerstitium. Double staining for apoptosis and AT2 receptor showed that most terminal dUTP nick-end labeling positive cells were found in tubules expressing AT2 receptor. Using an antibody that recognizes the active form caspase-3, we observed an increment in caspase-3 activation in rats receiving BSA with respect to those receiving saline. Rats with persistent proteinuria showed a diminution in the phosphorylation of Bcl-2 with respect to UNX-controls both at day 8 and day 28. By contrast, no changes were observed either in the Bax or in the Bcl-2 protein levels. The administration of BSA to UNX rats induced a diminution in the phosphorylation of ERK with respect to UNX-control at all times studied. The changes observed in ERK activities took place without alterations of ERK1/2 protein levels. In summary, our data suggest that persistent proteinuria causes apoptosis in tubular cells through the activation of AT2 receptor, which can, in turn, inhibit MAP kinase (ERK1/2) activation and Bcl-2 phosphorylation.

Animals↗
PubMed2004

Paracetamol-induced renal tubular injury: a role for ER stress.

Paracetamol (also known as acetaminophen) causes acute and chronic renal failure. While the mechanisms leading to hepatic injury have been extensively studied, the molecular mechanisms of paracetamol-induced nephrotoxicity are poorly defined. Paracetamol induced cell death with features of apoptosis in murine proximal tubular epithelial cells. While paracetamol increased the expression of the death receptor Fas on the cell surface, the Fas pathway was not involved in the paracetamol-induced apoptosis of tubular cells. The mitochondrial pathway was not activated during paracetamol-induced apoptosis; there was no dissipation of mitochondrial potential or release of apoptogenic factors such as cytochrome c or Smac/DIABLO. However, paracetamol-induced apoptosis is a caspase-dependent process that involves activation of caspase-9 and caspase-3 in the absence of cytosolic cytochrome c or Smac/DIABLO. The authors also detected induction of endoplasmic reticulum (ER) stress, characterized by GADD153 upregulation and translocation to the nucleus, as well as caspase-12 cleavage. Interestingly, after treatment of murine tubular cells with paracetamol and calpain inhibitors, the caspase-12 cleavage product was still detectable, and calpain inhibitors were unable to protect tubular cells from paracetamol-induced apoptosis. The results suggest that induction of apoptosis may underlie the nephrotoxic potential of paracetamol and identify ER stress as a therapeutic target in nephrotoxicity.

Acetaminophen↗
PubMed2004

Tight blood pressure control decreases apoptosis during renal damage.

BACKGROUND: An excess rate of apoptosis could lead to the gradual loss of renal mass. In this study, we investigated the role of apoptosis in the renal damage secondary to hypertension. METHODS: Spontaneously hypertensive rats with 5/6 renal mass reduction (subtotal nephrectomy) were distributed to receive no-treatment, 200 mg/L quinapril, 360 mg/L losartan, or triple therapy (200 mg/L hydralazine, 4 mg/L reserpine, and 100 mg/L hydrochlorothiazide) for 5 weeks. Sham-operated spontaneously hypertensive rats served as controls. Age-matched Wistar-Kyoto (WKY) rats, with or without subtotal nephrectomy, were also studied. RESULTS: Nontreated spontaneously hypertensive rats + subtotal nephrectomy developed proteinuria, glomerular sclerosis, and tubulointerstitial lesions. In comparison to spontaneously hypertensive rats, an increment in the number of [proliferating cell nuclear antigen (PCNA)]-positive and apoptotic [terminal deoxynucleotidyl transferase (Tdt)-mediated deoxyuridine triphosphate biotin nick end labeling (TUNEL)]-positive tubular and glomerular cells was observed. By contrast, WKY + subtotal nephrectomy rats showed less severe morphologic lesions, and only the number of proliferating cells increased. By Western blot, an up-regulation of renal Bax (apoptosis inducer) was noted both in spontaneously hypertensive rats + subtotal nephrectomy and WKY + subtotal nephrectomy rats. By contrast, Bcl-xL (apoptosis protector) was up-regulated in WKY + subtotal nephrectomy rats but not in spontaneously hypertensive rats + subtotal nephrectomy. The administration of appropriate doses of quinapril, losartan, or triple therapy to spontaneously hypertensive rats + subtotal nephrectomy normalized systolic blood pressure, partially prevented proteinuria, renal lesions and apoptosis, and decreased Bax, but no changes were noted in Bcl-xL. The Bax/Bcl-xL index was significantly increased in spontaneously hypertensive rats + subtotal nephrectomy compared to sham-operated spontaneously hypertensive rats and decreased in treated groups. CONCLUSION: The combination of renal mass reduction and hypertension caused severe renal lesions associated to an increment of apoptosis rate, mainly in tubular epithelial cells. Tight blood pressure control decreased the apoptosis rate and morphologic lesions. These studies suggest that changes in the expression of apoptosis-regulatory genes contribute to the progressive damage in hypertensive rats with renal mass reduction.

Animals↗
PubMed2003

Targeting apoptosis in acute tubular injury.

Recent research has shown that apoptosis and its regulatory mechanisms contribute to cell number regulation in acute renal failure. Acute tubular necrosis is the most frequent form of parenchymal acute renal failure. The main causes are ischemia-reperfusion, sepsis and nephrotoxic drugs. Exogenous factors such as nephrotoxic drugs and bacterial products, and endogenous factors such as lethal cytokines promote tubular cell apoptosis. Such diverse stimuli engage intracellular death pathways that in some cases are stimulus-specific. We now review the role of apoptosis in acute renal failure, the potential molecular targets of therapeutic intervention, the therapeutic weapons to modulate the activity of these targets and the few examples of therapeutic intervention on apoptosis.

Acute Disease↗
PubMed2003

Is word recognition different in central and peripheral vision?

Peripheral vision plays an important role in normal reading, but its role becomes larger for visually impaired people with central-field loss. This experiment studied whether lexical processing differs in central and peripheral vision through the analysis of word-frequency effects in lexical decisions. We asked two main questions: (1) Do central and peripheral vision differ in the time course of lexical processing? and (2) do central and peripheral vision differ in the quality of lexical processing? To address the first question, we examined the time course of frequency effects in central and peripheral vision over a range from 25 to 500 ms. We found that significant frequency effects occurred for the shortest exposures, 25-50 ms, in central vision, whereas significant frequency effects did not occur in peripheral vision until 100 ms. To address the second question, we used word-frequency effects as a marker for the nature of lexical processing. We compared frequency effects in central and peripheral vision for data within matched ranges of percent accuracy (0-20%, 20-40%, 40-60%, 60-80%, and 80-100%). We found that there was no difference in the pattern of frequency effects in central and peripheral vision at equivalent performance levels. We conclude that lexical processing is slower in peripheral vision, but the quality of lexical processing is similar in central and peripheral vision.

Adolescent↗
PubMed2003

Regulation of apoptosis by lethal cytokines in human mesothelial cells.

BACKGROUND: Dysregulation of peritoneal cell death may contribute to the complications of peritoneal dialysis (PD). Chronic peritoneal dialysis and acute peritonitis are both associated with loss of mesothelial cells. In addition, acute peritonitis is characterized by sudden changes in the number of peritoneal leukocytes. However, the factors regulating peritoneal cell survival are poorly understood. METHODS: Peritoneal effluent cells and mesothelial cells cultured from peritoneal dialysis patients were studied. Reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometry were used to assess the expression of FasL and Fas mRNA and protein. Western blot was used to assess FasL and tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL). RT-PCR was used to study TRAIL and TRAIL receptor mRNA. Apoptosis was quantified by flow cytometry of DNA content and confirmed by morphology. RESULTS: Apoptotic cells, including apoptotic mesothelial cells, were present in the peritoneal effluent of stable peritoneal dialysis patients and patients with bacterial peritonitis. The lethal cytokines FasL and TRAIL were expressed by peritoneal effluent cells, while cultured mesothelial cells expressed FasL, Fas, and TRAIL receptors. Cultured mesothelial cells were sensitive to FasL-induced apoptosis. IFNgamma increased the cell surface expression of Fas and the sensitivity of mesothelial cells to FasL-induced apoptosis. In contrast to the effect of FasL, TNFalpha and TRAIL did not induce apoptosis in human mesothelial cells from peritoneal dialysis patients. CONCLUSION: Lethal cytokines, such as FasL, may contribute to peritoneal cell turnover and the loss of mesothelium in peritoneal dialysis. The role of other cytokines, such as TRAIL, remains undefined. Approaches in limiting mesothelial cell injury that interferes with apoptosis should be considered.

Aged↗
PubMed2003

Bcl-xL overexpression protects from apoptosis induced by HMG-CoA reductase inhibitors in murine tubular cells.

BACKGROUND: Hyperplasia is attributed to enhanced tubular cell proliferation with unbalanced cell death. The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors induce apoptosis in a variety of cell lines, including proximal tubular cells. However, the mechanisms by which statins induce apoptosis in tubular cells have not been fully addressed. METHODS: Apoptosis induced by simvastatin was measured in murine tubular cells with and without overexpressing Bcl-xL. Expression of genes implicated in cell death was studied by Northern and Western blot. RESULTS: The treatment of proliferating murine tubular cells (MCT) with simvastatin induced apoptosis in a time- and dose-dependent manner (0.1 to 1 micromol/L). Apoptosis was correlated with Bcl-xL mRNA and protein down-regulation. By contrast, the treatment with simvastatin did not modify the expression of the proapoptotic protein Bax. Simvastatin treatment was associated with cytochrome C release from the mitochondria to the cytosol. We also observed the presence of active caspase 9 and 3 during apoptosis induced by simvastatin. These effects were reversed by mevalonate, farnesylpyrophosphate (FPP), and geranylgeranylpyrophosphate (GGPP), suggesting the involvement of protein prenylation. Simvastatin appears to alter the balance between cell-life and death-promoting genes, as reflected by the decreased Bcl-xL/Bax ratio. Supporting this hypothesis, overexpression of Bcl-xL reduced the amount of apoptosis induced by simvastatin by 80% when compared with control vector-expressing cells. The overexpression of Bcl-xL also prevented the activation of caspase 9 and 3. CONCLUSION: Our results indicate that down-regulation of Bcl-xL expression mediates apoptosis induced by statins in tubular cells. These results may be relevant to the treatment of disorders characterized by altered tubular proliferation.

Acute-Phase Proteins↗
PubMed2003

Expression of Smac/Diablo in tubular epithelial cells and during acute renal failure.

BACKGROUND: Apoptosis contributes to tubular cell loss in the course of renal injury. However, the mechanisms regulating tubular cell apoptosis are not well understood. Smac/Diablo is a mitochondrial protein that is released to the cytosol during apoptosis, where it blocks the antiapoptotic activity of inhibitor of apoptosis proteins (IAPs). METHODS: We have studied the regulation of Smac/Diablo mRNA and protein expression in murine toxic acute tubular necrosis, and in cultured tubular epithelial cells exposed to the lethal cytokine tumor necrosis factor (TNF). RESULTS: Folic acid-induced acute renal failure was associated with tubular cell apoptosis. Smac/Diablo mRNA and protein levels increased by 50% at 24 hours. TNF, a cytokine whose renal expression increases in folic acid nephropathy, induced apoptosis in cultured tubular epithelial cells in a time-dependent manner. In addition, TNF increased the mRNA and protein expression of Smac/Diablo. CONCLUSION: These findings support the concept that regulation of Smac/Diablo mRNA and protein expression is a mechanism by which lethal stimuli amplify their lethal potential in renal cells.

Acute Kidney Injury↗