Luminal Alkalinization Attenuates Proteinuria-Induced Oxidative Damage in Proximal Tubular Cells

Souma, Tomokazu; Abe, Michiaki; Moriguchi, Takashi; Takai, Jun; Yanagisawa-Miyazawa, Noriko; Shibata, Etsuro; Akiyama, Yasutoshi; Toyohara, Takafumi; Suzuki, Takehiro; Tanemoto, Masayuki; Abe, Takaaki; Sato, Hiroshi; Yamamoto, Masayuki; Ito, Sadayoshi

doi:10.1681/asn.2009111130

Cited by 31 publications

(25 citation statements)

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“…SB probably through correcting metabolic acidosis, then indirectly decreased the oxidative stress level. 17 The present study found in the field of lowering AOPP content, NAC was superior to PDTC and SB, PDTC and SB was superior to TH ( Figure 1C). AOPP is the product of plasma albumin and chlorine oxide, and is regarded as a novel marker of protein oxidative damage.…”

Section: Discussionsupporting

confidence: 54%

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Antioxidant therapy improves non-thyroidal illness syndrome in uremic rats

Yang

2016

Renal Failure

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Background The roles of antioxidant therapy on non-thyroidal illness syndrome (NTIS) in uremic rats is still unclear. Materials and methods Twenty-four Sprague-Dawley (SD) rats were randomly divided into blank, 5/6 nephrectomy (Nx), pyrrolidine dithiocarbamate (PDTC, 10 mg/100 g), sodium bicarbonate (SB, 0.1 g/100 g), N-acetylcysteine (NAC, 80 mg/100 g) and thyroid hormones (TH, levothyroxine 2 mg/100 g) groups. The serum levels of malondialdehyde (MDA), superoxide dismutase (SOD), advanced oxidation protein products (AOPP), interleukin (IL)-1b, free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) were detected in the sixth week. The expressions of IL-1b and deiodinase type 1 (DIO1) were assessed by western blotting. The nuclear factor kappa B (NF-kB) inflammatory signal pathway was confirmed by electrophoretic mobility shift assay (EMSA). Results Compared with 5/6 Nx group, PDTC and NAC significantly reduced the levels (p50.01, respectively) of serum MDA, AOPP, TSH, and elevated levels of serum SOD (p50.01, respectively) and FT3 (p ¼ 0.016 and p50.01). Neither had significant effects on serum IL-1b content (p ¼ 0.612 and p ¼ 0.582). PDTC and NAC markedly decreased the protein expression of IL-1b (p50.01) and increased the protein expression of DIO1 (p50.01), respectively. Both had been considerably blunted NF-kB activity (p50.01). Conclusions In uremic rat model, PDTC and NAC can effectively improve oxidative stress level and NTIS. In terms of improving oxidative stress level, NAC is probably superior to PDTC.

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Section: Discussionsupporting

confidence: 54%

“…13,14,[17][18][19] At present, there is no study that explores the effects of PDTC and NAC on NTIS in uremic rats. Firstly, the present study showed the impact of PDTC and NAC on NTIS in 5/6 Nx rats.…”

Section: Discussionmentioning

confidence: 99%

Antioxidant therapy improves non-thyroidal illness syndrome in uremic rats

Yang

2016

Renal Failure

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“…In view of the above findings, it appears that PUS is a condition where OS increases in the RPTs due to obesity and other factors (Ogawa et al 2015b), and where Nrf2 activity is increased to counteract such increased OS. A lower UpH itself increases OS in the RPTs (Souma et al 2011), indicating a possibility that lowered UpH and increased OS in the RPTs may create a vicious cycle. In diabetes, moreover, a reduction in UpH is related to persistent renovascular disorders (Ogawa et al 2015a).…”

Section: Discussionmentioning

confidence: 99%

The Reduction in Urinary Glutamate Excretion Is Responsible for Lowering Urinary pH in Pink Urine Syndrome

Ogawa

Takiguchi

Shimizu

et al. 2016

Tohoku J. Exp. Med.

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We frequently encounter brownish-red, cloudy urine in some obese subjects, which occurs due to pink urine syndrome (PUS). PUS is a phenomenon in which uric acid precipitates into the urine due to reduced urinary pH (UpH). The mechanism underlying urinary acidification has not been elucidated so far. UpH level is adjusted by urinary excretion of ammonia synthesized from glutamate or glutamine, suggesting that renal synthesis of ammonia from glutamate or glutamine is decreased in PUS. However, this hypothesis has not been examined yet. We therefore examined the changes in the urinary excretion of these amino acids in PUS. One-hundred-fifty male students who had undergone a physical examination were enrolled. To determine the presence [PUS (+), n = 72] or absence [PUS (−), n = 78] of PUS, urinary amino acid excretion and UpH were evaluated. Independent risk factors of lower UpH were determined using multiple regression analyses. The PUS (+) subjects, who had lower UpH values than PUS (-) subjects, showed lower urinary excretion of glutamate and some other glucogenic amino acids. Thus, UpH correlated positively with the urinary excretion of glutamate in the PUS (+) subjects. A reduction in urinary glutamate but not in glutamine excretion proved to be an independent risk factor for reduced UpH. In conclusion, PUS appears to occur when a reduction in the synthesis of ammonia from glutamate causes a decrease in UpH. Our results showed that urinary glutamate excretion was reduced in PUS because renal glutamate was consumed by a reaction different from ammonia production.

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“…12 It has been demonstrated that the oleic acidbound albumin enhances the production of superoxide through the activation of NADPH oxidase in renal proximal tubular cells. 13 Oleic acid-bound albumin is a major component of FFA-albumin in the serum and urine of patients with CKD. 14 Importantly, ROS such as H 2 O 2 and ONOO 2 are independents activator of AMPK.…”

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confidence: 99%

“…11 Increased peritoneal glucose absorption could also lead to adverse outcomes through weight gain and worsening of lipid abnormalities; however, evidence evaluating these potential mechanisms is inconsistent. [12][13][14] Moreover, the only study to examine the relationship between the magnitude of glucose absorption and patient outcomes was unable to demonstrate any association with either risk for death or a need for transfer to hemodialysis. 15 It also remains uncertain whether the higher risk for death or transfer to hemodialysis in individuals with a higher prescribed PD glucose concentration is a consequence of systemic glucose absorption or a reflection of low residual renal function or inadequate ultrafiltration capacity.…”

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confidence: 99%

Proximal Tubules Forget “Self-Eating” When They Meet Western Meals

Inoki

2013

Journal of the American Society of Nephrology

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Autophagy is an evolutionarily conserved cellular catabolic process in which cytoplasmic components are isolated from the rest of the cell within double-membrane structures (autophagosomes) and degraded through lysosomal degradation. Autophagy is activated under conditions of metabolic stress in which there is a shortage of energy for cells to maintain cellular homeostasis. 1 A number of recent studies demonstrated that the induction of autophagy serves a crucial role in protecting renal proximal tubular cells from many stresses, including ischemia/ reperfusion and nephrotoxic agents. 2-4 However, few studies have examined the role of proteinuria in the regulation of autophagy and the conditions that impair the activity of autophagy in the course of renal dysfunction. By characterizing an albumin-overload mice model and tissues from obese patients with proteinuria, Yamahara and coworkers, as described in this issue of JASN, 5 present evidence that autophagy plays an important role in protecting renal proximal tubular cells from harmful proteinuria. They demonstrated that proteinuria is a strong cue for autophagy induction in the proximal tubular cells of mice with albumin overload. Furthermore, high-fat diet and obesity blunt proteinuria-induced autophagy induction in the proximal tubules and thereby exacerbate tubular cell damage by proteinuria.The term "autophagy" is derived from the Greek words "phagy," meaning eat, and "auto," meaning self. Interestingly, this "self-eating" behavior was first discovered in renal proximal tubular cells of newborn mice in 1957. 6 Dr. Clark described the observations of autophagy in his paper:The large round bodies in the proximal tubules consist of an amorphous material and contain concentrically lamellar structures and mitochondria. They resemble the cytoplasmic droplets produced in the proximal tubules of adult rats and mice by the administration of proteins. The large round bodies disappear from the proximal tubules of infant mice during the first week after birth, but the concentric lamellar structure may be found in adult mice.From these observations, Clark hypothesized that the formation of the large round bodies (autophagosome) in the proximal tubules was likely due to the absorption of proteins that passed through immature newborn glomeruli. Now, Yamahara and coworkers have re-evaluated the process of renal tubular autophagy first described more than a half-century ago using their modern technologies under clinically relevant conditions.Compared with control mice, mice lacking autophagy activity in the renal proximal tubular cells displayed more severe damage of their tubular cells in response to free fatty acid (FFA)-albumin-induced proteinuria. Furthermore, the renoprotective activity of proteinuria-induced autophagy in proximal tubular cells was suppressed in obese mice and humans. Yamahara and coworkers found that the activation of 59AMP-activating protein kinase (AMPK) but not the enhanced endoplasmic reticulum stress played a critical role in the induction of aut...

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Luminal Alkalinization Attenuates Proteinuria-Induced Oxidative Damage in Proximal Tubular Cells

Cited by 31 publications

References 54 publications

Antioxidant therapy improves non-thyroidal illness syndrome in uremic rats

Antioxidant therapy improves non-thyroidal illness syndrome in uremic rats

The Reduction in Urinary Glutamate Excretion Is Responsible for Lowering Urinary pH in Pink Urine Syndrome

Proximal Tubules Forget “Self-Eating” When They Meet Western Meals

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