Raman Spectroscopy Using a Multiclass Extension of Fisher-Based Feature Selection Support Vector Machines (FFS-SVM) for Characterizing In-Vitro Apoptotic Cell Death Induced by Paclitaxel

Intracellular pathways leading from membrane receptor engagement to apoptotic cell death are still poorly characterized. We investigated the intracellular signaling generated after cross-linking of CD95 (Fas/Apo-1 antigen), a broadly expressed cell surface receptor whose engagement results in triggering of cellular apoptotic programs. DX2, a new functional anti-CD95 monoclonal antibody was produced by immunizing mice with human CD95-transfected L cells. Crosslinking of CD95 with DX2 resulted in the activation of a sphingomyelinase (SMase) in promyelocytic U937 cells, as well as in other human tumor cell lines and in CD95-transfected murine cells, as demonstrated by induction of in vivo sphingomyelin (SM) hydrolysis and generation of ceramide. Direct in vitro measurement of enzymatic activity within CD95-stimulated U937 cell extracts, using labeled SM vesicles as substrates, showed strong SMase activity, which required pH 5.0 for optimal substrate hydrolysis. Finally, all CD95-sensitive cell lines tested could be induced to undergo apoptosis after exposure to cell-permeant C2-ceramide. These data indicate that CD95 cross-linking induces SM breakdown and ceramide production through an acidic SMase, thus providing the first information regarding early signal generation from CD95, and may be relevant in defining the biochemical nature of intracellular messengers leading to apoptotic cell death.

Download Full-text

Radar Emitter Signal Recognition Based on Feature Selection and Support Vector Machines

Lecture Notes in Computer Science - Advances in Intelligent Computing ◽

10.1007/11538059_74 ◽

2005 ◽

pp. 707-716 ◽

Cited By ~ 2

Author(s):

Gexiang Zhang ◽

Zhexin Cao ◽

Yajun Gu ◽

Weidong Jin ◽

Laizhao Hu

Keyword(s):

Feature Selection ◽

Support Vector Machines ◽

Support Vector ◽

Signal Recognition ◽

Vector Machines

Download Full-text

Dapagliflozin Alleviates Renal Fibrosis by Inhibiting RIP1-RIP3-MLKL-Mediated Necroinflammation in Unilateral Ureteral Obstruction

Frontiers in Pharmacology ◽

10.3389/fphar.2021.798381 ◽

2022 ◽

Vol 12 ◽

Author(s):

Mei Ying Xuan ◽

Shang Guo Piao ◽

Jun Ding ◽

Qi Yan Nan ◽

Mei Hua Piao ◽

...

Keyword(s):

Cell Death ◽

Ureteral Obstruction ◽

Renal Fibrosis ◽

Apoptotic Cell ◽

Subsequent Development ◽

Unilateral Ureteral Obstruction ◽

Apoptotic Cell Death ◽

Inflammasome Activation ◽

Renal Tubular

Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, offers renoprotection in diabetes. However, potential for use in nondiabetic kidney disease remains unknown. Herein, we assessed whether dapagliflozin alleviates renal fibrosis by interfering with necroinflammation in a rat model of unilateral ureteral obstruction (UUO) and in vitro. After induction of UUO, rats were administered dapagliflozin daily for seven consecutive days. UUO induced significant renal tubular necrosis and overexpression of RIP1-RIP3-MLKL axis proteins; these coincided with NLRP3 inflammasome activation, and subsequent development of renal fibrosis. Oxidative stress caused by UUO is tightly associated with endoplasmic reticulum stress and mitochondrial dysfunction, leading to apoptotic cell death through Wnt3α/β-catenin/GSK-3β signaling; all of which were abolished by both dapagliflozin and specific RIP inhibitors (necrostatin-1 and GSK872). In H2O2-treated HK-2 cells, dapagliflozin and RIP inhibitors suppressed overexpression of RIP1-RIP3-MLKL proteins and pyroptosis-related cytokines, decreased intracellular reactive oxygen species production and apoptotic cell death, whereas cell viability was improved. Moreover, activated Wnt3α/β-catenin/GSK-3β signaling was inhibited by dapagliflozin and Wnt/β-catenin inhibitor ICG-001. Our findings suggest that dapagliflozin ameliorates renal fibrosis by inhibiting RIP1-RIP3-MLKL-mediated necroinflammation via Wnt3α/β-catenin/GSK-3β signaling in UUO.

Download Full-text