Glutamine attenuates tubular cell apoptosis in acute kidney injury via inhibition of the c-Jun N-terminal kinase phosphorylation of 14-3-3*

Kim, Yoon Sook; Jung, Myeong Hee; Choi, Mee Young; Kim, Young Hee; Sheverdin, Vadim; Kim, Jin Hyun; Ha, H.; Park, Dong Jun; Kang, Sang Soo; Cho, Gyeong Jae; Choi, Wan Sung; Chang, Se-Ho

doi:10.1097/ccm.0b013e3181a005ba

Cited by 49 publications

(39 citation statements)

References 70 publications

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“…Low serum prealbumin levels, a marker of nutritional status, were correlated with increased mortality in adults with AKI (44), and sustained improvement in prealbumin levels was associated with improved survival in adult hemodialysis patients (45). Systemic administration of protein in the form of amino acids early in the course of experimental AKI in small animal models of nephrotoxic and septic AKI had antiinflammatory and antiapoptotic effects in the renal tubular epithelium and may reverse AKI (46,47). Adults with oliguric AKI who were given intravenous amino acid infusions have a faster rate of renal recovery and higher survival than patients who were given isocaloric carbohydrates alone (48).…”

Section: Discussionmentioning

confidence: 99%

Nutrition Support among Critically Ill Children with AKI

Kyle

Akcan-Arikan

Orellana

et al. 2013

Clinical Journal of the American Society of Nephrology

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SummaryBackground Critically ill children are at high risk of underfeeding and AKI, which may lead to further nutritional deficiencies. This study aimed to determine the adequacy of nutrition support during the first 5 days of intensive care unit (ICU) stay. Results Of the 167 patients, 102 were male and 65 were female (median age 1.4 years). Using the RIFLE criteria, 102 (61%) patients had no AKI, whereas 44 (26%) were classified as category R (risk), 12 (7%) as category I (injury), and 9 (5%) as category F (failure). The median 5-day energy intake was lower relative to estimated BMR. Overall protein provision (19%) was lower than energy provision (55%) compared with estimated needs (P,0.001). I/F patients were more likely to be fasted versus receiving enteral/parenteral nutrition (n=813 patient days) and to receive ,90% of BMR (n=832 patient days) than No AKI/R patients.Conclusions Underfeeding, common in critically ill children, was accentuated in AKI. Protein underfeeding was greater than energy underfeeding in the first 5 days of PICU stay. Efforts should be made to provide adequate nutrition in ICU patients with AKI.

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Section: Discussionmentioning

confidence: 99%

Nutrition Support among Critically Ill Children with AKI

Kyle

Akcan-Arikan

Orellana

et al. 2013

Clinical Journal of the American Society of Nephrology

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“…The previous studies have shown that Gln improves the antioxidant defenses in patients [3][4][5]127] and attenuates apoptosis in experimental rat [6][7][8]128]. The enterocytes in the small intestine convert the most of Gln in diet and plasma to Ala, Cit and Pro that are released into the blood circulation in Gln-supplementation mammalian [9][10][11][12].…”

Section: Effects Of the Combination Of Ala Cit And Pro On • Oh-inducmentioning

confidence: 99%

“…Studies demonstrated that Gln improves clinical antioxidant outcome in patients [3][4][5] and attenuates apoptosis in experimental rat [6][7][8]. The anti-oxidative and anti-apoptotic effects of Gln may be closely associated with its metabolites in mammalian.…”

Section: Introductionmentioning

confidence: 99%

The metabolites of glutamine prevent hydroxyl radical-induced apoptosis through inhibiting mitochondria and calcium ion involved pathways in fish erythrocytes

Jiang

Liu

et al. 2016

Free Radical Biology and Medicine

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a b s t r a c tThe present study explored the apoptosis pathways in hydroxyl radicals ( • OH)-induced carp erythrocytes. Carp erythrocytes were treated with the caspase inhibitors in physiological carp saline (PCS) or Ca 2 þ -free PCS in the presence of 40 μM FeSO 4 /20 μM H 2 O 2 . The results showed that the generation of reactive oxygen species (ROS), the release of cytochrome c and DNA fragmentation were caspase-dependent, and Ca 2 þ was involved in calpain activation and phosphatidylserine (PS) exposure in • OH-induced carp erythrocytes. Moreover, the results suggested that caspases were involved in PS exposure, and Ca 2 þ was involved in DNA fragmentation in • OH-induced fish erythrocytes. These results demonstrated that there might be two apoptosis pathways in fish erythrocytes, one is the caspase and cytochrome c-dependent apoptosis that is similar to that in mammal nucleated cells, the other is the Ca 2 þ -involved apoptosis that was similar to that in mammal non-nucleated erythrocytes. So, fish erythrocytes may be used as a model for studying oxidative stress and apoptosis in mammal cells. Furthermore, the present study investigated the effects of glutamine (Gln)'s metabolites [alanine (Ala), citrulline (Cit), proline (Pro) and their combination (Ala 10 Pro 4 Cit 1 )] on the pathways of apoptosis in fish erythrocytes. The results displayed that Ala, Cit, Pro and Ala 10 Pro 4 Cit 1 effectively suppressed ROS generation, cytochrome c release, activation of caspase-3, caspase-8 and caspase-9 at the physiological concentrations, prevented Ca 2 þ influx, calpain activation, PS exposure, DNA fragmentation and the degradation of the cytoskeleton and oxidation of membrane and hemoglobin (Hb) and increased activity of anti-hydroxyl radical (AHR) in • OH-induced carp erythrocytes. Ala 10 Pro 4 Cit 1 produced a synergistic effect of inhibited oxidative stress and apoptosis in fish erythrocytes. These results demonstrated that Ala, Cit, Pro and their combination can protect mammal erythrocytes and nucleated cells against oxidative stress and apoptosis. The studies supported the use of Gln, Ala, Cit and Pro as oxidative stress and apoptosis inhibitors in mammal cells and the hypothesis that the inhibited effects of Gln on oxidative stress and apoptosis are at least partly dependent on that of its metabolites in mammalian.

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“…8 Significant progress in understanding the role of apoptosis and its triggering factors has been made in the last decade. Many growth factors (such as hepatocyte growth factor, α-melanocytestimulating hormone, erythropoietin and colony-stimulating-factor-1) [9][10][11][12][13] and drugs (such as glutamine and furosemide) 14,15 have been confirmed to attenuate AKI by inhibiting the apoptosis of renal tubular cells. In contrast, bortezomib and rapamycin aggravated AKI by enhancing tubular cell apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Augmenter of Liver Regeneration Attenuates Tubular Cell Apoptosis in Acute Kidney Injury in Rats: The Possible Mechanisms

Liao

Chen

et al. 2012

Renal Failure

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Augmenter of liver regeneration (ALR), the expression of which increased in rat kidneys after renal ischemia/reperfusion (I/R) injury, enhances renal tubular cell regeneration in vivo and in vitro. We aimed to investigate the effects of ALR on apoptosis of renal tubular cells after renal I/R injury in vivo and consider the possible mechanisms. Rats that were subjected to bilateral renal ischemia for 60 min followed by reperfusion were administered with either vehicle or recombinant human ALR (rhALR). Renal dysfunction and histologic injury were assessed by the measurement of serum biochemical markers and histological grading. Apoptosis was assessed by terminal deoxynucleotidyl transferasemediated dUTP-biotin nick-end labeling (TUNEL). Caspase-3 activity was measured using a colorimetric protease assay. Expression of Bcl-2, Bax Fas, phosphorylated-Akt (p-Akt), and phosphorylated-p53 (p-p53) was determined by western blotting. Compared with vehicle-treated rats, renal dysfunction and histologic injury were significantly attenuated by administration of rhALR. The number of TUNEL-positive tubular cells and caspase-3 activity were decreased, Bcl-2 and p-Akt expression was up-regulated, and Bax and p-p53 expression was down-regulated by administration of rhALR. However, administration of rhALR had no effect on Fas protein expression. These results indicate that the protective effect of rhALR on renal I/R injury is associated with its anti-apoptotic action in renal tubular cells. RhALR inhibits apoptosis by increasing the ratio of Bcl-2 to Bax and by decreasing the activity of caspase-3. The activation of Akt and inactivation of p53 are involved in the rhALR anti-apoptosis process.

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Glutamine attenuates tubular cell apoptosis in acute kidney injury via inhibition of the c-Jun N-terminal kinase phosphorylation of 14-3-3*

Abstract: A signaling link between JNK and 14-3-3 and subsequent mitochondrial death pathway may partly act as an early signaling that promotes apoptotic cell death leading to AKI, and glutamine may at least partially prevent apoptosis via enhancing Hsp70 or GSH levels.

Cited by 49 publications

References 70 publications

Nutrition Support among Critically Ill Children with AKI

Nutrition Support among Critically Ill Children with AKI

The metabolites of glutamine prevent hydroxyl radical-induced apoptosis through inhibiting mitochondria and calcium ion involved pathways in fish erythrocytes

Augmenter of Liver Regeneration Attenuates Tubular Cell Apoptosis in Acute Kidney Injury in Rats: The Possible Mechanisms

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