Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.60 (caspase-7)
 920 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pyrrolidine dithiocarbamate (PDTC) is widely used in pesticides, fungicides, insecticides, and herbicides. Copper (Cu) is a toxic heavy metal in the environment, and an essential trace metal element in the body, which is involved in many biological processes as a catalytic cofactor. The present study is designed to investigate the cellular toxicity of PDTC, CuCl(2), and PDTC/Cu complex exposure in lung alveolar epithelial cells that serve primary structural and functional roles in the lungs. The results showed that PDTC or CuCl(2) alone did not affect cell viability, but PDTC/Cu complex significantly decreased lung alveolar epithelial cell viability. PDTC/Cu complex also significantly increased intracellular copper concentration, but PDTC or CuCl(2) alone had low levels of copper. PDTC/Cu complex dramatically enhanced the JNK protein phosphorylation and ERK protein phosphorylation proteins. PDTC/Cu complex did not affect the p38 protein phosphorylation. PDTC/Cu complex was capable of activating the apoptosis-related caspases including caspase-9, caspase-7, and caspase-3, which could be reversed by the addition of JNK inhibitor SP600125 or transfection of MAPK8 short hairpin RNA. PDTC/Cu complex also increased cytosolic cytochrome c and decreased mitochondrial transmembrane potential. The Bcl-2 mRNA and protein expressions were decreased in lung epithelial cells treated with PDTC/Cu complex, which could be reversed by SP600125. Furthermore, PDTC/Cu complex could trigger the expressions of ER stress-associated signaling molecules including Grp78, Grp94, caspase-12, ATF4, and CHOP, which could be reversed by SP600125. Taken together, these results indicate that exposure to PDTC/Cu complex induces cytotoxicity and apoptosis in alveolar epithelial cells via the mitochondria- and ER-stress-related signaling pathways.
 ...
PMID:Pyrrolidine dithiocarbamate (PDTC)/Cu complex induces lung epithelial cell apoptosis through mitochondria and ER-stress pathways. 2092 May 58

Recent data highlight the presence, in HIV-1-seropositive patients with lymphoma, of p17 variants (vp17s) endowed with B-cell clonogenicity, suggesting a role of vp17s in lymphomagenesis. We investigated the mechanisms responsible for the functional disparity on B cells between a wild-type p17 (refp17) and a vp17 named S75X. Here, we show that a single Arginine (R) to Glycine (G) mutation at position 76 in the refp17 backbone (p17R76G), as in the S75X variant, is per se sufficient to confer a B-cell clonogenic potential to the viral protein and modulate, through activation of the PTEN/PI3K/Akt signaling pathway, different molecules involved in apoptosis inhibition (CASP-9, CASP-7, DFF-45, NPM, YWHAZ, Src, PAX2, MAPK8), cell cycle promotion and cancer progression (CDK1, CDK2, CDK8, CHEK1, CHEK2, GSK-3 beta, NPM, PAK1, PP2C-alpha). Moreover, the only R to G mutation at position 76 was found to strongly impact on protein folding and oligomerization by altering the hydrogen bond network. This generates a conformational shift in the p17 R76G mutant which enables a functional epitope(s), masked in refp17, to elicit B-cell growth-promoting signals after its interaction with a still unknown receptor(s). Our findings offer new opportunities to understand the molecular mechanisms accounting for the B-cell growth-promoting activity of vp17s.
 ...
PMID:A single amino acid substitution confers B-cell clonogenic activity to the HIV-1 matrix protein p17. 2874 58