As an opportunistic bacterial pathogen, Pseudomonas aeruginosa mainly affects immunocompromised individuals as well as patients with cystic fibrosis. In a previous study, we showed that ExoS of P. aeruginosa, when injected into host cells through a type III secretion apparatus, functions as an effector molecule to trigger apoptosis in various tissue culture cells. Here, we show that injection o...

Microtubule disruption by colchicine induces apoptosis in selected neuronal populations. However, little is known about the upstream death signalling events mediating the neurotoxicity. We investigated first whether colchicine-induced granule cell apoptosis activates the c-Jun N-terminal kinase (JNK) pathway. Cultured murine cerebellar granule cells were exposed to 1 microm colchicine for 24 h....

Sensory hair cells undergo apoptosis following exposure to aminoglycoside antibiotics. In neurons, apoptosis is associated with a transient increase in intracellular Ca2+, phosphorylation of the transcription factor c-Jun, and the release of cytochrome c from mitochondria into the cytosol, which along with other cofactors results in the activation of caspases. To examine the possible role of th...

Oxidative stress, which is found in pancreatic beta-cells in the diabetic state, suppresses insulin gene transcription and secretion, but the signaling pathways involved in the beta-cell dysfunction induced by oxidative stress remain unknown. In this study, subjecting rat islets to oxidative stress activates JNK, p38 MAPK, and protein kinase C, preceding the decrease of insulin gene expression....

Epidermal growth factor (EGF) plays a major role in non-small cell lung cancer cell autocrine growth and has been reported to activate the JUN kinase/stress-activated protein kinase (JNK/SAPK) pathway in model cells. Activation of JNK/SAPK leads to the phosphorylation of c-JUN protooncogene on serines 63 and 73. This mechanism is required for and cooperates in the transformation of rat embryo f...

The low frequency of p53 alterations e.g., mutations/deletions (∼10%) in multiple myeloma (MM) makes this tumor type an ideal candidate for p53-targeted therapies. RITA is a small molecule which can induce apoptosis in tumor cells by activating the p53 pathway. We previously showed that RITA strongly activates p53 while selectively inhibiting growth of MM cells without inducing genotoxicity, in...

PURPOSE To investigate whether exposure of human corneal epithelial cells to hyperosmotic stress activates the c-Jun NH(2)-terminal kinase (JNK) stress-activated protein kinase (SAPK) pathway, and stimulates production of the matrix metalloproteinases (MMPs): gelatinase (MMP-9), collagenases (MMP-1 and -13), and stromelysin (MMP-3). METHODS Primary human corneal epithelial cells cultured in n...

Purpose: To investigate the therapeutic effect and underlying mechanism of hypaphorine in a cellular model non-alcoholic fatty liver disease (NAFLD).Methods: Palmitic acid (PA) was used to induce NAFLD phenotype hepatocytes. Cell viability apoptosis were evaluated by CCK-8 flow cytometry assays. Inflammatory response measured enzyme-linked immunosorbent assay (ELISA). The on lipid accumulation ...

The ether phospholipid 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3; edelfosine) is a potent inducer of apoptosis in human tumor cells. We show that ET-18-OCH3-induced apoptosis is associated with activation of the c-Jun NH2-terminal kinase (JNK) signaling. The addition of ET-18-OCH3 to distinct human leukemic cells (HL-60, U937, and Jurkat), which undergo rapid apoptosis o...

Stress conditions and proinflammatory cytokines activate the c-Jun NH2-terminal kinase (JNK), a member of the stress-activated group of mitogen-activated protein kinases (MAPKs). We recently demonstrated that inhibition of JNK signaling with the use of the islet-brain (IB) 1 and 2 proteins prevented interleukin (IL)-1 –induced pancreatic -cell death. Bioactive cell-permeable peptide inhibitors ...