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

In this study, we aimed to determine the growth inhibition and the induction of apoptotic cell death brought about by the herb Anemarrhena asphodeloides Bunge in gastric cancer cell lines, and to clarify the mechanism of this apoptosis. Water-soluble ingredients of A. asphodeloides, and the gastric cancer cell lines, MKN45 and KATO-III, were used in vitro. Growth inhibition, induction of cell death, morphological features, the presence of DNA ladders, increases in caspase-3-like activity, the effects of a caspase-3 inhibitor on apoptotic cell death, and the release of cytochrome c by A. asphodeloides were analyzed. A. asphodeloides inhibited the growth and decreased the viability of the gastric cancer cell lines. The viability of normal skin fibroblasts in the presence of low concentrations of A. asphodeloides was higher than that of gastric cancer cells. Apoptotic bodies and DNA ladders were observed to be induced in MKN45 and KATO-III by A. asphodeloides. The caspase 3 inhibitor, Ac-DEVD-CHO, inhibited the apoptotic cell death of gastric cancer cells induced by A. asphodeloides. The caspase 3-like activity in MKN45 and KATO-III cells increased after the addition of A. asphodeloides. Cytochrome c was released from mitochondria into the cytosol 8 h after the addition of A. asphodeloides, and reached a peak at 16 h. The peak of cytochrome c release was earlier than that of caspase 3-like activity. We concluded that A. asphodeloides inhibited the growth of the gastric cancer cell lines MKN45 and KATO-III and induced apoptosis. The apoptosis of MKN45 and KATO-III cells induced by A. asphodeloides was associated with the release of cytochrome c from the mitochondria, followed by an increase in caspase 3-like activity.
 ...
PMID:Growth inhibition and apoptosis of gastric cancer cell lines by Anemarrhena asphodeloides Bunge. 1122 75

Hwansodan has been used as a prescription for senile and vascular dementia in Oriental medicine. We investigated the neuroprotective effects of Hwansodan water extract on the apoptotic death of PC12 cells by serum deprivation. Hwansodan significantly rescued PC12 cells from apoptotic death by serum deprivation in a dose-dependent manner. The nuclear staining of PC12 cells clearly showed that Hwansodan attenuated nuclear condensation and fragmentation, which represents typical neuronal apoptotic characteristics. Hwansodan also prevents DNA fragmentation and caspase-3-like protease activation in serum-deprived PC12 cells and induces the tyrosine phosphorylation of proteins around 44 kDa, which was identified as ERK1 with electrophoretic gel mobility shift by Western blot. In addition, MEK inhibitor PD98059 and Ras inactivator, alpha-hydroxyfarnesylphosphonic acid and mevastatin, attenuated the neuroprotective effects of Hwansodan in serum-deprived PC12 cells. These results indicate that Ras/MEK/ERK signaling pathway plays a role in neuroprotective effects of Hwansodan in serum-deprived PC12 cells.
 ...
PMID:Hwansodan protects PC12 cells against serum-deprivation-induced apoptosis via a mechanism involving Ras and mitogen-activated protein (MAP) kinase pathway. 1128 16

Decreased phosphorylation of focal adhesion kinase (FAK) is associated with loss of focal adhesions and actin stress fibers and precedes the onset of apoptosis in renal epithelial cells caused by nephrotoxicants (Van de Water, B., Nagelkerke, J. F., and Stevens, J. L. (1999) J. Biol. Chem. 274, 13328-13337). The role of FAK in the control of apoptosis caused by nephrotoxicants was further investigated in LLC-PK1 cells that were stably transfected with either green fluorescent protein (GFP)-FAK or dominant negative acting deletion mutants of FAK, GFP-FAT, and GFP-FRNK. GFP-FAT and GFP-FRNK delayed the formation of focal adhesions and prevented the localization of endogenous (phosphorylated) FAK at these sites. GFP-FAT and GFP-FRNK overexpression potentiated the onset of apoptosis caused by the nephrotoxicant dichlorovinyl-cysteine. This was associated with an increased activation of caspase-3. GFP-FAT also potentiated apoptosis caused by doxorubicin but not cisplatin. The potentiation of apoptosis by GFP-FAT was related to an almost complete dephosphorylation of FAK; this did not occur in cells overexpressing only GFP. This dephosphorylation was associated with a pronounced loss of focal adhesion organization in GFP-FAT cells, in association with loss of tyrosine phosphorylation of paxillin. In conclusion, the data indicate an important role of cell-matrix signaling in the control of chemically induced apoptosis; loss of FAK activity caused by toxic chemicals results in perturbations of focal adhesion organization with a subsequent inactivation of associated (signaling) molecules and loss of survival signaling.
 ...
PMID:Suppression of chemically induced apoptosis but not necrosis of renal proximal tubular epithelial (LLC-PK1) cells by focal adhesion kinase (FAK). Role of FAK in maintaining focal adhesion organization after acute renal cell injury. 1144 17

The diazo compound, 2,2'-azobis [2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPC), is a water-soluble radical initiator that can be activated at mild temperatures (37 degrees -40 degrees C). Potential biomedical applications of this compound include the fabrication of hydrogels by radical polymerization (e.g., cell encapsulation or drug delivery) and the thermal sensitization of cancerous cells to induce localized cell death. In this study we evaluated whether this compound could induce cell death at 37 degrees C in vitro and in vivo using a tumor animal model. Cytotoxicity was quantitated with a sulfo-rhodamine B colorimetric assay by monitoring growth inhibition of human glioma cells in vitro. AIPC was entrapped in fibrin gel and exposed to cells in culture as a potential way to localize the compound in a controlled release environment. The mechanism of action for cell death was evaluated by quantitating caspase-3 activity in cells. In vivo studies included human glioma tumors that were grown subcutaneously in rats to study the effect of intra-tumor injections of AIPC. AIPC was also injected subcutaneously into normal tissue. Concentrations of 0.2% and 0.02% (w/v in RPMI medium) showed 93% and 84% inhibition of cell growth in vitro, respectively. Cell-growth inhibition using gel-entrapped AIPC was comparable to that obtained with AIPC in solution after 48 hr (86% inhibition at 0.2% w/v). Exposure to AIPC resulted in a significant increase of caspase activity (up to 163 units after 20 min), suggesting induced apoptosis as a possible mechanism of action of the AIPC. Histological pictures showed that, relative to normal tissue, cancerous tissue was more sensitive to the effects of AIPC.
 ...
PMID:Cell-killing potential of a water-soluble radical initiator. 1151 51

The effect of melatonin on age-related thymic involution and apoptosis induced by hydroxyl radicals (*OH) in mouse thymocyte cultures was investigated. Exogenous melatonin was administered in the drinking water (15 microg/mL) of 7-month-old male Balb/c mice for 40 consecutive days. Our results show that melatonin distinctly reversed the age-related thymic involution as revealed by the notable increase of cellular density, particularly the number of thymocytes, percentage of thymocytes at G2+S phases and the younger morphological appearance as a whole when compared with control animals. More strikingly, the recovery of these morphometric parameters were maintained for 30 days after the termination of melatonin administration suggesting that the re-established homeostasis by melatonin may last for a longer time. At the same time, when primary culture of thymocytes was preincubated with 200 microM melatonin before their exposure to hydroxyl radicals (*OH) generated by Fe(2+)-mediated Fenton reaction, apoptotic cell death induced by *OH was almost completely prevented as determined by both flow cytometric analysis and the TUNEL assay. DNA laddering assay also documented the inhibition of thymocyte apoptosis by melatonin. Furthermore, we found that the *OH-induced increment of caspase-3 activity in thymocytes was completely abolished by melatonin preincubation. Taken together, our study indicates that in addition to other mechanisms, melatonin may also directly act as an antioxidant via attenuating apoptotic thymocyte death caused by free radicals and stimulates thymocyte proliferation in thymus and thus to rejuvenate the degenerative organ.
 ...
PMID:Rejuvenation of degenerative thymus by oral melatonin administration and the antagonistic action of melatonin against hydroxyl radical-induced apoptosis of cultured thymocytes in mice. 1158 55

The repair of damaged gastric mucosa is a complex process involving prostaglandins (PG) and mucosal growth factors such as epidermal growth factor (EGF). Recently, we postulated that the increased occurrence of apoptosis in the gastric epithelium might be of pathophysiological importance in the development of stress lesions. The aim of the present study was to assess the effect of the pretreatment of rats, exposed to 3.5 h of water immersion and restraint stress (WRS), with EGF and PG (16,16 dmPGE(2)) on the number of stress lesions, recovery of gastric mucosa from stress and the expression of apoptosis related genes such as caspase-3 and antiapoptotic bcl-2. Rats were divided in following groups: (1) vehicle; (2) EGF 100 microg/kg i.p.; (3) 16,16 dm-PGE(2) (5 microg/kg i.g.) and caspase-1 inhibitor (ICE-I; 100 microg/kg i.p.). One hour later, the rats were exposed to 3.5 h of WRS and then sacrificed immediately (0 h) or at 6, 12, or 24 h after WRS. The number of acute gastric lesions was determined. Gastric epithelial apoptosis was assessed by TUNEL staining. In addition, mRNA expression of caspase-3, Bcl-2 and proinflammatory cytokines (IL-1 beta, TNFalpha) was assessed by RT-PCR. PGE(2) generation in gastric mucosa and luminal EGF were determined by RIA. Exposure to WRS resulted in the development of multiple acute stress erosions ( approximately 18) which almost completely healed during 24 h. The gastric blood flow was significantly reduced (approximately 70% of intact mucosa) immediately after WRS. The expression of mRNA for IL-1 beta and TNF alpha reached their peak at 12 h after stress exposure. The apoptosis rate was highest at 6 h after WRS and was accompanied by the highest caspase-3 expression. In rats pretreated with EGF or 16,16 dm-PGE(2), a significant decrease in caspase-3 mRNA and upregulation of bcl-2 mRNA as observed as compared to vehicle controls. Caspase-1 inhibitor significantly reduced the number of stress lesions. We conclude that EGF and PGE(2) accelerate healing of stress-induced lesions due to the attenuation of apoptosis via upregulation of bcl-2 in gastric mucosa. Inhibitors of apoptosis accelerate healing of stress lesions and may be potentially effective agents in the healing of damaged gastric mucosa.
 ...
PMID:Epidermal growth factor and prostaglandin E(2) accelerate mucosal recovery from stress-induced gastric lesions via inhibition of apoptosis. 1159 61

Caspases are believed to play a key role in the delayed neuronal cell death observed in the rat brain after hypoxic-ischemic (HI) insult. Caspase inhibitors have been developed as antiapoptotic agents. Hippocampal damage after HI insult is strongly related to tissue temperature, and systemic hypothermia has been introduced clinically for brain protection. In this study, we examined the effects of a caspase inhibitor and systemic hypothermia on neuronal protection in the developing rat brain. Postnatal d 7 rat pups were subjected to the Rice model of hypoxia for 1 h. Systemic hypothermia was induced with a water bath at 29 degrees C. Before HI insult, a pan-caspase inhibitor, boc-aspartyl-(OMe)-fluoromethyl-ketone (BAF), was injected into the cerebral ventricle. The ipsilateral hippocampus was subjected to caspase assays and histologic assessment. The HI group at 37 degrees C (HI-37 degrees C) showed a peak of caspase-3 activity 16 h after insult. This activity was significantly reduced in the presence of BAF or hypothermia (HI-29 degrees C group, p < 0.05) or by the combination of HI-29 degrees C + BAF (p < 0.01 versus HI-37 degrees C). The number of neuronal cells in the ipsilateral hippocampal CA1 region in the HI-37 degrees C group was significantly decreased (62.9% versus control). The number of neuronal cells was maintained in the HI-37 degrees C + BAF group (82.7%), the HI-29 degrees C group (78.7%), and the combination group (95.2%) (p < 0.05 versus HI-37 degrees C). A combination of systemic hypothermia and BAF produced a strong protective effect against neuronal damage in the developing rat brain, along with a reduction in caspase-3 activity.
 ...
PMID:Combination effect of systemic hypothermia and caspase inhibitor administration against hypoxic-ischemic brain damage in neonatal rats. 1164 53

Carbofuran (CF) is one of the most widely used carbamate pesticides in the world applied for insect and nematode control. Due to its widespread use in agriculture and households, contamination of food, water, and air has become serious, and consequently adverse health effects are inevitable in humans, animals, wildlife and fish. It has been reported that CF alone or in combination with other carbamate insecticides influences the level of reproductive and metabolic hormones such as thyroxine and corticosterone, and results in impairment of endocrine, immune and behavioral functions. In this study, we evaluated the effects of CF and its metabolite, the N-nitroso derivative N-nitrosocarbofuran (NOCF), on genotoxicity, cell growth, cell cycle and apoptosis of Chinese hamster lung fibroblast (CHL) cells. NOCF, but not CF, induced genotoxicity determined by Ames test. NOCF inhibited the growth of Chinese hamster lung fibroblast (CHL) cells with an IC(50) of 12.8 microM. NOCF induced apoptosis of CHL cells, which was demonstrated by morphological changes, DNA fragmentation and flow cytometric analysis. Treatment of CHL cells with NOCF induced significant G(2)/M cell cycle arrest. Caspase-3, an executioner of apoptosis was also activated by the treatment of CHL cells with NOCF. These results suggest that NOCF, that is an important metabolite of CF, leads to the induction of cell cycle arrest and apoptosis in CHL cells.
 ...
PMID:N-nitrosocarbofuran, but not carbofuran, induces apoptosis and cell cycle arrest in CHL cells. 1171 56

Necrosis and apoptosis coexist in the thyroid during goitre development and involution, but little is known about their respective causes. To test the possible role of free radicals, we analysed separately necrosis and apoptosis in male Wistar rats with depressed or normal antioxidant protection. Vitamin E-deficient and -sufficient rats were made goitrous with perchlorate in drinking water; involution was induced by repeated injection of NaI, without or with methimazole. Increase of thyroid malondialdehyde concentration and decrease of glutathione peroxidase activity confirmed the depressed antioxidant protection in vitamin E-deficient rats. Plasma thyroxine and TSH levels were not modified. Necrosis (swollen cells) and apoptosis (pyknotic cells) were quantified on histological sections. In vitamin E-sufficient rats, dead cells were very rare in control thyroids, increased 3-fold in goitre and still further during involution. Necrotic epithelial cells predominated in the goitre and their number declined after iodide supplementation, without or with methimazole. In contrast, the number of apoptotic cells and the caspase-3 activity were increased in goitre and further increased after involution, with two-thirds of pyknotic cells being observed in the interstitium. Apoptosis was prevented by methimazole. Vitamin E deficiency significantly increased total cell death and epithelial cell necrosis and induced the occurrence of much cell debris in the follicular lumen during involution, with no modification of the apoptotic reaction. These results show that the type of cell death is differentially regulated during goitre development and involution: necrosis is related to the oxidative status of the cells, while apoptosis comes with iodine-induced involution.
 ...
PMID:Cell necrosis and apoptosis are differentially regulated during goitre development and iodine-induced involution. 1183 55

Hemodialysis patients exhibit a defective immune response leading to an increased susceptibility of infections and neoplasms. Far from being helpful, dialytic therapy per se also may be responsible for this acquired immunodeficiency. Dialysis membranes and bacterial products present in dialysis water may trigger and even perpetuate an abnormal mononuclear cell activation. Upon contact with cellulosic dialysis membranes, monocytes display an increased expression of surface markers of cell activation, such as adhesion molecules CD18, CD49, CD54 and the lipopolysaccharide (LPS) ligand (CD14). Moreover, proinflammatory cytokines as IL-1beta and TNF-alpha are released both in vivo and in vitro when monocytes are exposed to cellulosic membranes. Of special interest is the fact that end-stage renal disease patients undergoing hemodialysis exhibit an increased mononuclear cell apoptosis. This apoptosis is directly related to the degree of biocompatibility of the dialysis membrane. Apoptosis is activated when monocytes enter in contact with the cellulosic dialysis membrane through cell surface receptors linked to G-proteins. In early steps of apoptosis signaling, pertussis toxin-sensitive G proteins are coupled to protein kinase C (PKC)-dependent phosphorylative mechanisms. Furthermore, recent evidence support that the execution phase of apoptosis is mediated by a caspase-3 dependent pathway. Finally, very recent available data support that monocytes subjected to repeated activation suffer a process of accelerated senescence, as demonstrated by the senescent phenotype (CD14 and CD32) expressed and their shortened telomeric length. This senescent profile may generage a defective cellular response in acute stress situations, explaining (at least in part) the altered immune response observed in hemodialysis patients.
 ...
PMID:Cell apoptosis and hemodialysis-induced inflammation. 1198 20


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>