Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.62 (caspase-9)
 7,507 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although Ocimum sanctum has been used extensively for its medicinal values in India and China, its antitumor activity against human nonsmall cell lung carcinoma (NSCLC) A549 cells has not been investigated until now. Therefore, the antitumor mechanism of ethanol extracts of Ocimum sanctum (EEOS) was elucidated in A549 cells in vitro and the Lewis lung carcinoma (LLC) animal model. EEOS exerted cytotoxicity against A549 cells, increased the sub-G1 population and exhibited apoptotic bodies in A549 cells. Furthermore, EEOS cleaved poly(ADP-ribose)polymerase (PARP), released cytochrome C into cytosol and simultaneously activated caspase-9 and -3 proteins. Also, EEOS increased the ratio of proapoptotic protein Bax/antiapoptotic protein Bcl-2 and inhibited the phosphorylation of Akt and extracellular signal regulated kinase (ERK) in A549 cancer cells. In addition, it was found that EEOS can suppress the growth of LLC inoculated onto C57BL/6 mice in a dose-dependent manner. Overall, these results demonstrate that EEOS induces apoptosis in A549 cells via a mitochondria caspase dependent pathway and inhibits the in vivo growth of LLC, suggesting that EEOS can be applied to lung carcinoma as a chemopreventive candidate.
 ...
PMID:Ocimum sanctum induces apoptosis in A549 lung cancer cells and suppresses the in vivo growth of Lewis lung carcinoma cells. 1927 50

Histone deacetylase (HDAC) inhibitors have recently been reported to have possible reno-protective effects in the last few years. In this study, we found that tricostatin A (TSA), an HDAC inhibitor, prevented transforming growth factor beta1 (TGF-beta1)-induced apoptosis in cultured human renal proximal tubular epithelial cells (RPTECs). TGF-beta1-induced apoptosis via the activation of both caspase-8 and caspase-9 but did not activate the Fas receptor and did not alter Bcl-2 or Bax protein expression. TSA prevented TGF-beta1-induced apoptosis and the activation of caspase-8 and caspase-9 in RPTECs but did not inhibit the TGF-beta1-induced phosphorylation of Smad3 and p38 mitogen-activated protein kinase (MAPK). However, TSA inhibited the TGF-beta1-induced phosphorylation of extracellular signal regulated kinase (ERK), and the MAPK/ERK kinase inhibitor U0126, which specifically inhibits ERK, also prevented TGF-beta1-induced apoptosis. Our results show, for the first time, that TSA inhibits TGF-beta1-induced ERK activation and overrides pro-apoptotic signals like Smad3 and p38 in human RPTECs.
 ...
PMID:Trichostatin a prevents TGF-beta1-induced apoptosis by inhibiting ERK activation in human renal tubular epithelial cells. 2055 9

Ulcerative colitis (UC), characterized by inflammation, oxidative stress, and increased intestinal epithelial cell apoptosis, is an immunologically mediated chronic intestinal disorder. The present study was aimed at investigating the protective effects of alpha-lipoic acid (ALA) against trinitrobenzene sulfonic acid (TNBS)-induced UC and the underlying mechanism. ALA of 80 mg/kg bw/day was administered by gastric gavage to mice for 7 days after TNBS-induced UC. Our data indicated that ALA effectively facilitated recovery of pathologic changes in the colon, as evidenced by a significant increase of body weight, decrease of colon mass index and histopathological score. Furthermore, ALA significantly inhibited TNBS-induced apoptosis, which partly due to up-regulation of Bcl-2 expression, reduction of Bax expression and caspase-3, caspase-9 activity. ALA reduced malondialdehyde (MDA), nitric oxide (NO), and inducible nitric oxide synthase (iNOS) levels, and restored superoxide dismutase (SOD) activity and glutathione (GSH) content in colon tissues from TNBS-challenged mice. Additionally, phosphorylation of extracellular signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 kinase (p38) in colon tissues were significantly inhibited by ALA treatment. In summary, we demonstrate that ALA has protective properties against TNBS-induced UC through anti-apoptosis, anti-oxidant actions, and mitogen-activated protein kinase (MAPK) signaling pathway. Our present findings suggest a therapeutic potential of ALA in UC.
...
PMID:Alpha-lipoic acid attenuates trinitrobenzene sulfonic acid-induced ulcerative colitis in mice. 2578 6

Background: The cardioprotective effect of propofol on ischemia-reperfusion injury (I/R injury) is partly due to suppressing apoptosis. Mitochondrial dynamics are also involved in apoptosis. Mitochondrial fusion and fission lead to mitochondrial morphological changes. However, whether suppressing apoptosis effect of propofol against ischemia-reperfusion injury in the heart is via regulating mitochondrial morphology remains unclear. Methods: H9c2 cells underwent oxygen glucose deprivation (OGD) followed by reperfusion to simulate cardiomyocytes ischemia/reperfusion injury. Cell viability, apoptosis ratio and intracellular reactive oxygen species (ROS) were assessed, respectively. Mitochondrial membrane dynamin family proteins, extracellular signal regulated kinase 1 and 2 (ERK1/2), phosphorylated extracellular signal regulated kinase 1 and 2 (p-ERK1/2) and proteins related to intrinsic apoptosis pathways were detected by western blotting. The mitochondrial morphology and the distribution of dynamin-related protein 1 (Drp1) were observed by using laser confocal microscopy. Results: Propofol enhanced the survival of H9c2 cells, decreased ROS levels and inhibited apoptosis during oxygen glucose deprivation/reperfusion (OGD/R) injury. Mitochondrial fission in H9c2 cells was inhibited by propofol during OGD injury. Propofol alleviated high levels of mitochondrial fusion and fission during OGD/R in H9c2 cells, by regulating mitochondrial membrane remodeling dynamin family proteins. Propofol inhibited Drp1 colocalization with mitochondria in H9c2 cells during OGD/R injury. Moreover, Drp1 phosphorylation was inhibited by propofol through decreasing ERK activation during OGD/R injury. We found that propofol ameliorated H9c2 cells apoptosis during OGD/R via inhibiting mitochondrial cytochrome c release and caspase-9, caspase-6, caspase-7 and caspase-3 activation. Conclusion: Propofol suppresses H9c2 cells apoptosis during OGD/R injury via inhibiting intrinsic apoptosis pathway, which may be partly due to reducing high levels of mitochondrial fusion and fission induced by OGD/R injury.
 ...
PMID:Propofol Ameliorates H9c2 Cells Apoptosis Induced by Oxygen Glucose Deprivation and Reperfusion Injury via Inhibiting High Levels of Mitochondrial Fusion and Fission. 3080 45