Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Farnesol (FOH) and other isoprenoid alcohols induce apoptosis in various carcinoma cells and inhibit tumorigenesis in several in vivo models. However, the mechanisms by which they mediate their effects are not yet fully understood. In this study, we show that FOH is an effective inducer of apoptosis in several lung carcinoma cells, including H460. This induction is associated with activation of several caspases and cleavage of poly(ADP-ribose) polymerase (PARP). To obtain insight into the mechanism involved in FOH-induced apoptosis, we compared the gene expression profiles of FOH-treated and control H460 cells by microarray analysis. This analysis revealed that many genes implicated in endoplasmic reticulum (ER) stress signaling, including ATF3, DDIT3, HERPUD1, HSPA5, XBP1, PDIA4, and PHLDA1, were highly up-regulated within 4 h of FOH treatment, suggesting that FOH-induced apoptosis involves an ER stress response. This was supported by observations showing that treatment with FOH induces splicing of XBP1 mRNA and phosphorylation of eIF2alpha. FOH induces activation of several mitogen-activated protein kinase (MAPK) pathways, including p38, MAPK/extracellular signal-regulated kinase (ERK) kinase (MEK)-ERK, and c-jun NH2-terminal kinase (JNK). Inhibition of MEK1/2 by U0126 inhibited the induction of ER stress response genes. In addition, knockdown of the MEK1/2 and JNK1/2 expression by short interfering RNA (siRNA) effectively inhibited the cleavage of caspase-3 and PARP and apoptosis induced by FOH. However, only MEK1/2 siRNAs inhibited the induction of ER stress-related genes, XBP1 mRNA splicing, and eIF2alpha phosphorylation. Our results show that FOH-induced apoptosis is coupled to ER stress and that activation of MEK1/2 is an early upstream event in the FOH-induced ER stress signaling cascade.
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PMID:Farnesol-induced apoptosis in human lung carcinoma cells is coupled to the endoplasmic reticulum stress response. 1769

Homocysteine-inducible endoplasmic reticulum stress-inducible ubiquitin-like domain member 1 protein (HERPUD1) is involved in endoplasmic reticulum stress response. Immense amounts of research showed HERPUD1 plays multiple roles in various models. In this work, we explored the role of HERPUD1 during the pathophysiological processes of intracerebral hemorrhage (ICH). Rat ICH model was established and verified by behavioral test. Western blot and immunohistochemistry revealed a significant up-regulation of HERPUD1 expression around the hematoma after ICH. Besides, the expression of cytochrome c (cyt c) and active caspase-3 increased accompanied to HERPUD1 expression. Double-labeled immunofluorescence indicated HERPUD1 mainly colocalized with neurons. Further study showed HERPUD1 silence brought about up-regulation of apoptosis markers including cyt c and active caspase-3 coupled with increased cell apoptosis in vitro model. All these findings suggested that HERPUD1 might play a protective role in ICH-induced neuronal apoptosis in rat models.
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PMID:Increased expression of HERPUD1 involves in neuronal apoptosis after intracerebral hemorrhage. 2787 50