Cytotoxic Potential of Proinflammatory Cytokines: Combined Deletion of TNF Receptors TNFR1 and TNFR2 Prevents Motoneuron Cell Death after Facial Axotomy in Adult Mouse

2002 ◽  
Vol 178 (2) ◽  
pp. 186-193 ◽  
Author(s):  
G Raivich
Keyword(s):  
Cell Death ◽  
Proinflammatory Cytokines ◽  
Adult Mouse ◽  
Tnf Receptors ◽  
Cytotoxic Potential ◽  
Motoneuron Cell

scholarly journals Targeted Disruption of the Mouse Caspase 8 Gene Ablates Cell Death Induction by the TNF Receptors, Fas/Apo1, and DR3 and Is Lethal Prenatally

Immunity ◽  
1998 ◽  
Vol 9 (2) ◽  
pp. 267-276 ◽  
Author(s):  
Eugene E Varfolomeev ◽  
Marcus Schuchmann ◽  
Victor Luria ◽  
Nuchanard Chiannilkulchai ◽  
Jacques S Beckmann ◽  
...  
Keyword(s):  
Cell Death ◽  
Caspase 8 ◽  
Tnf Receptors ◽  
Targeted Disruption

scholarly journals Dual modulation of cell survival and cell death by  2-adrenergic signaling in adult mouse cardiac myocytes

2001 ◽  
Vol 98 (4) ◽  
pp. 1607-1612 ◽  
Author(s):  
W.-Z. Zhu ◽  
M. Zheng ◽  
W. J. Koch ◽  
R. J. Lefkowitz ◽  
B. K. Kobilka ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Survival ◽  
Cardiac Myocytes ◽  
Adult Mouse ◽  
Adrenergic Signaling

scholarly journals Urinary acrolein metabolite levels in severe acute alcoholic hepatitis patients

2019 ◽  
Vol 316 (1) ◽  
pp. G115-G122 ◽  
Author(s):  
Vatsalya Vatsalya ◽  
Maiying Kong ◽  
Leila Gobejishvili ◽  
Wei-Yang Chen ◽  
Sanjay Srivastava ◽  
...  
Keyword(s):  
Cell Death ◽  
Liver Disease ◽  
Proinflammatory Cytokines ◽  
Alcoholic Hepatitis ◽  
Pathogenic Role ◽  
Cytokeratin 18 ◽  
Acute Alcoholic Hepatitis ◽  
Noninvasive Biomarker ◽  
Liver Cell Death

Alcohol-associated liver disease (ALD) remains a major health concern worldwide. Alcohol consumption gives rise to reactive/toxic acrolein, a pathogenic mediator of liver injury in experimental ALD. Elevated acrolein adducts and metabolites are detectable in blood and urine. This study evaluates the major urinary acrolein metabolite, 3-hydroxypropylmercapturic acid (HPMA), in patients with acute alcoholic hepatitis (AAH) and examines its association with disease severity and markers of hepatic inflammation and injury. Urine HPMA was significantly higher in patients with severe [model for end-stage liver disease (MELD) ≥ 20] AAH compared with nonsevere AAH (MELD ≤ 19) or non-alcohol-consuming controls, suggesting that urine HPMA is a novel noninvasive biomarker in severe AAH. The association between HPMA and MELD in patients with AAH was nonlinear. In patients with nonsevere AAH, there was a positive trend, although not significant, whereas in severe AAH the association was negative, indicative of extensive injury and glutathione depletion. Consistent with the multifactorial etiology of ALD, our data identified strong combined effects of HPMA and proinflammatory cytokines on hepatocyte cell death, thereby supporting the pathogenic role of acrolein in liver injury. HPMA, together with IL-1β, showed robust associations with cytokeratin 18 caspase-cleaved fragment (CK18-M30; adjusted R2 = 0.812, P = 0.016) and cytokeratin 18 full-length protein (CK18-M65; adjusted R2 = 0.670, P = 0.048); similarly, HPMA, with IL-8, correlated with CK18-M30 (adjusted R2 = 0.875, P = 0.007) and CK18-M65 (adjusted R2 = 0.831, P = 0.013). The apoptosis index (CK18-M30:CK18-M65 ratio) strongly correlated with HPMA, together with IL-1β (adjusted R2 = 0.777, P = 0.022) or tumor necrosis factor-α (TNFα; adjusted R2 = 0.677, P = 0.046). In patients with severe AAH, IL-1β, IL-8, and TNFα are the predominant proinflammatory cytokines that interact with HPMA and play important mediating roles in influencing the extent/pattern of liver cell death. NEW & NOTEWORTHY This is the first study to examine the urinary acrolein metabolite 3-hydroxypropylmercapturic acid (HPMA) in alcoholic liver disease. HPMA was higher in patients with severe acute alcoholic hepatitis (AAH) compared with controls or nonsevere AAH and may be a novel selective, noninvasive biomarker for severe AAH. Consistent with the multifactorial etiology of alcohol-associated liver disease, we identified strong combined effects of HPMA and proinflammatory cytokines (IL-1β, IL-8, and TNFα) on the extent/pattern of liver cell death, thereby supporting the pathogenic role of acrolein.

Rat motoneuron cell death in development correlates with loss of N-methyl-d-aspartate receptors

2002 ◽  
Vol 330 (2) ◽  
pp. 131-134 ◽  
Author(s):  
N. Hori ◽  
Y. Tan ◽  
N.L. Strominger ◽  
D.O. Carpenter
Keyword(s):  
Cell Death ◽  
Motoneuron Cell

scholarly journals PPAR-γ Activation Prevents Septic Cardiac Dysfunction via Inhibition of Apoptosis and Necroptosis

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Shiyan Peng ◽  
Junmei Xu ◽  
Wei Ruan ◽  
Suobei Li ◽  
Feng Xiao
Keyword(s):  
Cell Death ◽  
Proinflammatory Cytokines ◽  
Cardiac Dysfunction ◽  
Myocardial Dysfunction ◽  
Cecal Ligation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Interacting Protein ◽  
Cardiac Inflammation ◽  
Ppar Γ

Sepsis-induced cardiac dysfunction remains one of the major causes of death in intensive care units. Overwhelmed inflammatory response and unrestrained cell death play critical roles in sepsis-induced cardiac dysfunction. Peroxisome proliferator-activated receptor- (PPAR-) γ has been proven to be cardioprotective in sepsis. However, the mechanism of PPAR-γ-mediated cardioprotection and its relationship with inflammation and cell death are unclear. We hypothesized that activation of PPAR-γ by reducing cardiac inflammation, myocardial apoptosis, and necroptosis may prevent myocardial dysfunction in sepsis. Rats were subjected to cecal ligation and puncture (CLP) with or without PPAR-γ agonist (rosiglitazone) or antagonist T0070907 (T007). After CLP, cardiac function was significantly depressed, which was associated with the destructed myocardium, upregulated proinflammatory cytokines, and increased apoptosis, necrosis, and necroptosis. This process is corresponded with decreased inhibitor κB (IκBα) and increased NF-κB, receptor-interacting protein kinase-1 (RIP1), RIP3, and mixed lineage kinase-like (MLKL) protein. Activation of PPAR-γ by rosiglitazone pretreatment enhanced PPAR-γ activity and prevented these changes, thereby improving the survival of septic rats. In contrast, inhibition of PPAR-γ by T007 further exacerbated the condition, dropping the survival rate to nearly 0%. In conclusion, PPAR-γ activation by reducing proinflammatory cytokines, apoptosis, and necroptosis in the myocardium prevents septic myocardial dysfunction.

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