Glutamine deficiency renders human monocytic cells more susceptible to specific apoptosis triggers

Exner, Ruth; Weingartmann, G.; Eliasen, Maja Munk; Gerner, Christopher; Spittler, Andreas; Roth, Erich; Oehler, Rudolf

doi:10.1067/msy.2002.118318

Cited by 43 publications

(25 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Glutamine deprivation also induced apoptosis in rat intestinal epithelial cells (32) and rendered premonocytic and HL-60 cells significantly more susceptible to Fas-mediated apoptosis (14,20). In agreement with these previous studies documenting the antiapoptotic activity of glutamine, both glutamine and alanyl-glutamine reduced the T84 cell apoptosis induced by TxA by almost 50% through blockage of caspase 8 activation.…”

Section: Discussionsupporting

confidence: 79%

Caspase and Bid Involvement inClostridium difficileToxin A-Induced Apoptosis and Modulation of Toxin A Effects by Glutamine and Alanyl-Glutamine In Vivo and In Vitro

Carneiro

Fujii

Brito³

et al. 2006

Infect Immun

102

View full text Add to dashboard Cite

Clostridium difficile is the leading cause of nosocomial bacterial diarrhea. Glutamine and its stable and highly soluble derivative alanyl-glutamine, have been beneficial in models of intestinal injury. In this study, we extend our work on the mechanisms of Clostridium difficile toxin A (TxA)-induced apoptosis in human intestinal epithelial T84 cells and evaluate the effects of glutamine and alanyl-glutamine on TxA-induced apoptosis in vitro and disruption of ileal mucosa in vivo. T84 cells were incubated with TxA (100 ng/ml) in medium with or without glutamine or alanyl-glutamine (3 to 100 mM). Apoptosis was evaluated by DNA fragmentation in vitro and the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labeling method in vivo. Caspase and Bid involvement were investigated by Western blotting. Ligated rabbit ileal loops were used for the evaluation of intestinal secretion, mucosal disruption, and apoptosis. TxA induced caspases 6, 8, and 9 prior to caspase 3 activation in T84 cells and induced Bid cleavage by a caspase-independent mechanism. Glutamine or alanyl-glutamine significantly reduced TxA-induced apoptosis of T84 cells by 47% and inhibited activation of caspase 8. Both glutamine and alanyl-glutamine reduced TxA-induced ileal mucosal disruption and secretion. Altogether, we further delineated the apoptosis-signaling cascade induced by TxA in T84 cells and demonstrated the protective effects of glutamine and alanyl-glutamine. Glutamine and alanyl-glutamine inhibited the apoptosis of T84 cells by preventing caspase 8 activation and reduced TxA-induced intestinal secretion and disruption.

show abstract

Section: Discussionsupporting

confidence: 79%

Caspase and Bid Involvement inClostridium difficileToxin A-Induced Apoptosis and Modulation of Toxin A Effects by Glutamine and Alanyl-Glutamine In Vivo and In Vitro

Carneiro

Fujii

Brito³

et al. 2006

Infect Immun

102

View full text Add to dashboard Cite

show abstract

“…The infection rate of SAP was 30%-50% [27][28][29][30] , leading to a mortality of 40%-80% [31,32] . Glutamine is used as a major fuel and nucleotide substrate for rapidly dividing cells such as intestinal mucosal cells and the gut-associated immunocytes [33][34][35][36][37] . Glutamine can prevent atrophy of the intestinal epithelial cells through HSP 70 generation [38] and improve the intestinal immune barrier [39][40][41] .…”

Section: Discussionmentioning

confidence: 99%

Impact of alanyl-glutamine dipeptide on severe acute pancreatitis in early stage

Xue

Deng²,

Xia³

et al. 2008

WJG

View full text Add to dashboard Cite

INTRODUCTIONAcute pancreatitis (AP) contributes to thousands of annual hospital admissions, of which severe acute pancreatitis (SAP) accounts for 10%-20% [1][2][3] . Despite considerable improvement in the treatment, the mortality of SAP still ranges between 10%-15% [2][3][4][5] . The course of SAP tends to be prolonged and the patients usually are hypermetabolic and high protein catabolic due to systemic inflammatory response syndrome (SIRS) induced by acute local inflammatory process and subsequent vital-organ dysfunction [6] . Thus, if nutritive support is not appropriately administrated to match rapidly increased demand in the treatment of SAP, the patients consequently come down with metabolic disorder and nutrition deficiency, which is considered to increase mortality due to impaired immune function, increased risk of infections and intractable vital-organ failure.In recent years, research showed a conditional deficiency of glutamine would be an independent predictive factor for a poor outcome and its correction improved survival by restoring cellular protective mechanisms, improving immune function and resistance of the gut barrier to hypoperfusion, metabolic stress and subsequent bacterial translocation, and decreasing the risk of infection in critical illness [7][8][9][10] . Since free glutamine is instable in solution, intravenous administration is limited [7] . Alanyl-glutamine METHODS:Eighty patients with SAP were randomized and received 100 mL/d of 20% AGD intravenously for 10 d starting either on the day of (early treatment group) or 5 d after (late treatment group) admission. Groups had similar demographics, underlying diseases, Ranson score, Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score, and Balthazar 's computed tomography (CT) score at the beginning of the study and underwent similar other medical and nutritional management. RESULTS:The duration of acute respiratory distress syndrome (2.7 ± 3.3 d vs 12.7 ± 21.0 d, P < 0.01), renal failure (1.3 ± 0.5 d vs 5.3 ± 7.3 d, P < 0.01), acute hepatitis (3.2 ± 2.3 d vs 7.0 ± 7.1 d, P < 0.01), shock (1.7 ± 0.4 d vs 4.8 ± 3.1 d, P < 0.05), encephalopathy (2.3 ± 1.9 d vs 9.5 ± 11.0 d, P < 0.01) and enteroparalysis (2.2 ± 1.4 d vs 3.5 ± 2.2 d, P < 0.01) and hospital stay (28.8 ± 9.4 d vs 45.2 ± 27.1 d, P < 0.01) were shorter in the early treatment group than in the late treatment group. The 15-d APACHE Ⅱ score was lower in the early treatment group than in the late treatment group (5.0 ± 2.4 vs 8.6 ± 3.6, P < 0.01). The infection rate (7.9% vs 26.3%, P < 0.05), operation rate (13.2% vs 34.2%, P < 0.05) and mortality (5.3% vs 21.1%, P < 0.05) in the early treatment group were lower than in the late treatment group.Xue P et al . Impact of AGD on SAP 475 www.wjgnet.com dipeptide (AGD), however, can be taken via vein and hydrolyzed into alanine and glutamine in circulation as a substitute [7] . Presently AGD supplement in parenteral nutrition is a worth-trying approach and an evidence-based recommendation in the management of SAP [11] , but ...

show abstract

“…During AP, especially SAP, body in high decomposition state needs a much greater energy demand. Nutrition deficiency or fasting during AP will cause the deficiency of Gln and arginine and less growth factors synthesized by epithelial cells of the intestinal mucosa, leading to regulating function disturbance of lymphocytes and macrophages (Foitzik et al, 1999;Exner et al, 2002) and the injury of the intestinal mucosa (Avgerinos et al, 2003). In addition, although sufficient energy and nitrogen source may be supplied by long-term total parenteral neruition (TPN), functional injury of the intestinal mucosa will still inevitably be caused by a shortage of nutrition required for repairing metabolism of the intestinal mucosa and digestion stimulation due to food shortage (Liu et al, 2001).…”

Section: Influence Of Enteral Nutrition Deficiency On Injury Of Intesmentioning

confidence: 99%

Mechanism of acute pancreatitis complicated with injury of intestinal mucosa barrier

Zhang

Song

et al. 2007

J. Zhejiang Univ. - Sci. B

View full text Add to dashboard Cite

Acute pancreatitis (AP) is a common acute abdomen in clinic with a rapid onset and dangerous pathogenetic condition.AP can cause an injury of intestinal mucosa barrier, leading to translocation of bacteria or endotoxin through multiple routes, bacterial translocation (BT), gutorigin endotoxaemia, and secondary infection of pancreatic tissue, and then cause systemic inflammatory response syndrome (SIRS) or multiple organ dysfunction syndrome (MODS), which are important factors influencing AP's severity and mortality. Meanwhile, the injury of intestinal mucosa barrier plays a key role in AP's process. Therefore, it is clinically important to study the relationship between the injury of intestinal mucosa barrier and AP. In addition, many factors such as microcirculation disturbance, ischemical reperfusion injury, excessive release of inflammatory mediators and apoptosis may also play important roles in the damage of intestinal mucosa barrier. In this review, we summarize studies on mechanisms of AP.

show abstract

Glutamine deficiency renders human monocytic cells more susceptible to specific apoptosis triggers

Cited by 43 publications

References 25 publications

Caspase and Bid Involvement inClostridium difficileToxin A-Induced Apoptosis and Modulation of Toxin A Effects by Glutamine and Alanyl-Glutamine In Vivo and In Vitro

Caspase and Bid Involvement inClostridium difficileToxin A-Induced Apoptosis and Modulation of Toxin A Effects by Glutamine and Alanyl-Glutamine In Vivo and In Vitro

Impact of alanyl-glutamine dipeptide on severe acute pancreatitis in early stage

Mechanism of acute pancreatitis complicated with injury of intestinal mucosa barrier

Contact Info

Product

Resources

About