Cyclooxygenase-independent inhibition of H2O2-induced cell death by S-ketoprofen in renal cells

2007 ◽  
Vol 55 (4) ◽  
pp. 295-302 ◽  
Author(s):  
Patricia Reyes-Martin ◽  
Matilde Alique ◽  
Trinidad Parra ◽  
Jaime Perez de Hornedo ◽  
Javier Lucio-Cazana
Keyword(s):  
Cell Death ◽  
Renal Cells

scholarly journals FP018MTOR INHIBITORS PROMOTE AUTOPHAGIC NOT APOPTOTIC CELL DEATH IN PROXIMAL TUBULAR RENAL CELLS, VIA P75NTR ACTIVATION

2015 ◽  
Vol 30 (suppl_3) ◽  
pp. iii71-iii71
Author(s):  
Simona Lupinacci ◽  
Giuseppina Toteda ◽  
Donatella Vizza ◽  
Anna Perri ◽  
Paolo Gigliotti ◽  
...  
Keyword(s):  
Cell Death ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Renal Cells ◽  
Proximal Tubular

Silymarin selectively protects human renal cells from cisplatin-induced cell death

2011 ◽  
Vol 49 (10) ◽  
pp. 1082-1090 ◽  
Author(s):  
Chuanpit Ninsontia ◽  
Kanittha Pongjit ◽  
Chatchai Chaotham ◽  
Pithi Chanvorachote
Keyword(s):  
Cell Death ◽  
Renal Cells

Regulation of Fas and Fas ligand expression in cultured murine renal cells and in the kidney during endotoxemia

1996 ◽  
Vol 271 (6) ◽  
pp. F1193-F1201 ◽  
Author(s):  
A. Ortiz-Arduan ◽  
T. M. Danoff ◽  
R. Kalluri ◽  
S. Gonzalez-Cuadrado ◽  
S. L. Karp ◽  
...  
Keyword(s):  
Cell Death ◽  
Renal Cell ◽  
Fas Ligand ◽  
Mesangial Cells ◽  
Receptor Expression ◽  
Tnf Alpha ◽  
Dependent Manner ◽  
Renal Cells ◽  
Ifn Gamma ◽  
Fas Mrna

Fas ligand (FasL) and Fas belong to a recently described family of cytokines and receptors with similarities to tumor necrosis factor (TNF) and its receptors. Upon engagement by specific antibodies or by FasL, Fas transduces a signal for apoptosis in permissive cells. Although apoptosis occurs during renal development and following injury to mature cells, the factors responsible for programmed renal cell death are uncertain. We have studied Fas expression by renal cells in vitro and during endotoxemia in mice. Several renal cell types, including glomerular mesangial cells and tubular epithelial cells express a Fas transcript in culture. Lipopolysaccharides (LPS), interleukin-1 beta, interferon-gamma (IFN-gamma), and TNF-alpha increase the levels of Fas mRNA in cultured mesangial and tubular cells. TNF-alpha and LPS raise the level of Fas mRNA in a time- and dose-dependent manner with Fas receptor expression peaking after 72 h of exposure to LPS. Anti-Fas antibodies can induce the death of cultured mesangial cells. This cell death shows the characteristic changes of apoptosis, including DNA fragmentation and pyknotic changes of the nucleus. Increases in Fas by LPS, TNF-alpha, and IFN-gamma enhance the killing induced by the anti-Fas antibody. FasL is also expressed by cultured renal cells, and TNF-alpha treatment of mesangial cells increases its expression. In vivo, Fas mRNA is present at low level in normal kidney. LPS increases the levels of Fas mRNA and protein in kidney and produces evidence of apoptosis along nephrons. These data suggest that transcripts encoding natural FasL and Fas are induced by LPS and may play a role in endotoxemia-induced acute renal failure and organ dysfunction.

Omi/HtrA2 protease mediates cisplatin-induced cell death in renal cells

2005 ◽  
Vol 288 (2) ◽  
pp. F371-F379 ◽  
Author(s):  
Lucia Cilenti ◽  
George A. Kyriazis ◽  
Mangala M. Soundarapandian ◽  
Valerie Stratico ◽  
Adam Yerkes ◽  
...  
Keyword(s):  
Cell Death ◽  
Proteolytic Activity ◽  
Renal Cell ◽  
Specific Inhibitor ◽  
Renal Cells ◽  
Proximal Tubule Cells ◽  
Primary Mouse ◽  
Apoptosis Proteins ◽  
Renal Cell Lines

Omi/HtrA2 is a mitochondrial proapoptotic serine protease that is able to induce both caspase-dependent and caspase-independent cell death. After apoptotic stimuli, Omi is released to the cytoplasm where it binds and cleaves inhibitor of apoptosis proteins. In this report, we investigated the role of Omi in renal cell death following cisplatin treatment. Using primary mouse proximal tubule cells, as well as established renal cell lines, we show that the level of Omi protein is upregulated after treatment with cisplatin. This upregulation is followed by the release of Omi from mitochondria to the cytoplasm and degradation of XIAP. Reducing the endogenous level of Omi protein using RNA interference renders renal cells resistant to cisplatin-induced cell death. Furthermore, we show that the proteolytic activity of Omi is necessary and essential for cisplatin-induced cell death in this system. When renal cells are treated with Omi's specific inhibitor, ucf-101, they become significantly resistant to cisplatin-induced cell death. Ucf-101 was also able to minimize cisplatin-induced nephrotoxic injury in animals. Our results demonstrate that Omi is a major mediator of cisplatin-induced cell death in renal cells and suggest a way to limit renal injury by specifically inhibiting its proteolytic activity.

Abstract 253: Inhibition of Necrosis Attenuates Blood Pressure and Renal Inflammation in Male SHR with no Effect in Females

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Olga Rafikova ◽  
Ashlee J Tipton ◽  
Babak Baban ◽  
Jennifer C Sullivan
Keyword(s):  
Blood Pressure ◽  
Flow Cytometry ◽  
Cell Death ◽  
Sex Differences ◽  
Th17 Cells ◽  
Renal Cells ◽  
Male And Female ◽  
Immune System Activation ◽  
Age Related ◽  
Renal Necrosis

Inflammation plays an important role in the pathogenesis of hypertension, and we recently published that male spontaneously hypertensive rats (SHR) have more pro-hypertensive, pro-inflammatory Th17 cells in their kidneys than females. However, the mechanisms initiating the inflammatory response remain unclear. Damage-associated molecular patterns (DAMPs) are released from dying cells and induce immune system activation. High mobility group box 1 (HMGB1) is a DAMP actively secreted by apoptotic cells in an oxidized form, or passively released by necrotic cells in a reduced form. Reduced HMGB1 has prolonged activity and is more pro-inflammatory. We hypothesized that sex differences in cell death contribute to sex differences in the immune cell profile and hypertension. Renal necrosis and apoptosis were measured by flow cytometry in 12 wk old male and female SHR. Male SHR have greater necrotic cell death (% total renal cells: 5.3±0.8 vs.1.0±0.4; p=0.004; N=6), while female SHR have more apoptosis (% total renal cells: 1.6±0.4 vs.4.0±0.4; p=0.004; N=4-5). Male SHR also had greater reduced HMGB1 in renal cortex compared to females (HMGB1 oxidized/reduced ratio: 1.0±0.1 vs. 1.7±0.1; p=0.002; N=6). We next measured blood pressure by telemetry in male and female SHR treated with vehicle or necrosis inhibitor NecroX-5 (1 mg/kg per day; 2 wks). The renal T cell and macrophage levels were measured by flow cytometry. NecroX-5 treatment in male SHR prevented age-related increases in blood pressure compared to vehicle-treated rats (ΔmmHg/week: 0.8±1.1 vs. 4.2±0.3; p=0.05; N=3). Necrox5 also significantly decreased renal necrosis (% total renal cells: 5.3±0.8 vs. 0.8±0.1; p=0.005; N=3-6), macrophages (% total renal cells: 2.8±0.6 vs. 0.8± 0.1; p=0.04; N=3-4), Th17 cells (% T cells: 4.5±0.3 vs. 2.7±0.3; p=0.009; N=3-4) and the pro-inflammatory cytokine IL-17 (% total renal cells: 10.0±0.4 vs. 5.3±0.7; p=0.002; N=3-4) in male SHR. NecroX-5 had no effect on blood pressure or pro-inflammatory markers in females. We conclude that necrosis is an important contributor in progression of hypertension in male SHR. Sex differences in cell death may contribute to sex differences in blood pressure and the immune profile.

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