Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Caspase 12”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 505 records · Page 28Linked to original sources
PubMed2006

Neuronal and glial apoptosis in human traumatic brain injury.

To establish reliable methods to aid the timing of brain damage after traumatic brain injury (TBI), brain tissue from 56 autopsy cases with TBI and known survival times, ranging from a few minutes to 126 days, were tested for apoptotic changes to the neuronal and glial cells. Apoptosis was established using the TdT-mediated dUTP nick end labelling (TUNEL) method of in-situ labelling and immunohistochemical reaction of caspase 3. In addition, cellular reaction and astroglial cell differentiation were investigated using histological and immunohistochemical markers. From a survival time of 120 min up to 12 days, TUNEL-positive apoptotic neuronal cells were frequently detected in the contusion zone. The earliest positive caspase 3 reaction in cortical neurons was evident after a posttraumatic interval of 80 min. Detection of apoptotic glial cells using the TUNEL technique showed that as in the case of neuronal cells, the earliest positive TUNEL reaction was obtained after 110 min. In cases of survival times of 120 min up to 4 days, apoptotic glial cells could frequently be detected. However, the first caspase 3-positive glial cells appeared 5 h after injury. Cerebral apoptosis was significantly associated with TBI cases as compared to control cases (P<0.001). The reference histological findings of neutrophilic granulocytes, CD3-positive T-lymphocytes, CD68-positive activated microglial cells/macrophages and TUNEL-positive neuronal cells increases the degree of certainty in determining the probable age of traumatic brain injury to 87.5%.

Adolescent↗
PubMed2006

[Inhibitory action of propyl gallate on the activation of SAPK/JNK and p38MAPK induced by cerebral ischemia-reperfusion in rats].

AIM: To explore the protective effect of propyl gallate against neuronal injury in the boundary zone of the infarction area in the rat cerebral ischemia-reperfusion model and its possible mechanism. METHODS: Transient focal ischemia induced by middle cerebral artery occlusion in the rats was established by ligation of the left internal carotid artery for 2 h. Rats were treated by propyl gallate with different doses (23.5, 47 and 94 micromol x kg(-1)) for three days before operation. Coronal brain sections were collected after 1 , 2, 4, 6, 12 and 24 h of reperfusion, neuronal injury in the boundary zone of the infarction area was evaluated by TUNEL and Nissl staining. The expression of activated Caspase-3, total SAPK/JNK, p38MAPK and their phosphorylation (Thr183/Tyr185, Thr180/Tyr182) was investigated by immunohistochemistry and Western blotting with corresponding antibodies. RESULTS: Although SAPK/JNK immunoreactivity did not increase at each time point in the boundary zone of the infarction area after reperfusion, p-SAPK/JNK immunoreactivity increased significantly at 1 h and then decreased gradually, and p38MAPK immunoreactivity was enhanced at each time point, peaked at 6 h. Expression of p-p38MAPK peaked at 6 h. Activated Caspase-3 immunoreactivity appeared at 6 h in the boundary zone of the infarction area and peaked at 12 h. TUNEL positive neurons were observed at 12 h and became more abundant at 24 h. The number of Nissl positive neurons decreased gradually and apoptosis ratio of neurons peaked at 24 h. Propyl gallate reduced the immunoreactivity of SAPK/JNK, p-SAPK/JNK, p38MAPK and p-p38MAPK markedly at 1 and 6 h. Propyl gallate with doses of 47 and 94 micromol x kg(-1) were more effective. CONCLUSION: Inhibition on the activation of SAPK/JNK and p38MAPK is the possible protective mechanism of propyl gallate against neuronal injury induced by cerebral ischemia-reperfusion.

Animals↗
PubMed2006

The magnitude and time-dependence of the apoptotic response of normal and malignant cells subjected to ionizing radiation versus hyperthermia.

PURPOSE: The purpose of the study was to examine the optimal time of exposure and dose of heat and ionizing radiation that results in the killing of human cancer cells in vitro via apoptosis vs. necrosis. MATERIALS AND METHODS: Human mammary carcinoma, colorectal carcinoma and normal bovine capillary endothelial (BCE) cell lines were subjected to 20 Gy ionizing radiation and 6, 12, 24, and 72 h later assessed for apoptosis using detection of apoptotic bodies and caspase assays. Necrosis was detected by loss of cells from the surface and lactate dehydrogenase (LDH) release. The colorectal carcinoma cells were subjected to hyperthermia using temperatures ranging from 39 - 44 degrees C for 5, 15 or 45 min. exposures and at varying times post-treatment, apoptosis and necrosis were measured. RESULTS: In response to ionizing radiation, none of the cells underwent necrosis and some cell types apoptosed 24 and 72 h posttreatment. The colorectal cancer cells exhibited a steady increase of apoptosis at 6, 12, and 24 h. When these cells were exposed to 40 degrees C for 5 min, caspases increased within 6 h and a significant fraction (50%) of cells apoptosed. If the time of exposure to 40 degrees C was increased to 15 or 45 min, 80% and 100% of the dying cells apoptosed, respectively. A temperature of 39 degrees C did not cause cell death even after 45 min exposures. If heat was elevated to 42 or 44 degrees C, increased necrosis was observed with a corresponding decrease in apoptosis. CONCLUSIONS: These studies reveal time and temperature dependent in vitro cell responses to ionizing radiation and water-bath hyperthermia.

Animals↗
PubMed1997

Activation of caspase-2 in apoptosis.

Members of the CED-3/interleukin-1beta-converting enzyme (ICE) protease (caspase) family are synthesized as proforms, which are proteolytically cleaved and activated during apoptosis. We report here that caspase-2 (ICH-1/NEDD-2), a member of the ICE family, is activated during apoptosis by another ICE member, a caspase-3 (CPP32)-like protease(s). When cells are induced to undergo apoptosis, endogenous caspase-2 is first cleaved into three fragments of 32-33 kDa and 14 kDa, which are then further processed into 18- and 12-kDa active subunits. Up to 50 microM N-acetyl-Asp-Glu-Val-Asp-aldehyde (DEVD-CHO), a caspase-3-preferred peptide inhibitor, inhibits caspase-2 activation and DNA fragmentation in vivo, but does not prevent loss of mitochondrial function, while higher concentrations of DEVD-CHO (>50 microM) inhibit both. In comparison, although the activity of caspase-3 is very sensitive to the inhibition of DEVD-CHO (<50 nM), inhibition of caspase-3 activation as marked by processing of the proform requires more than 100 microM DEVD-CHO. Our results suggest that the first cleavage of caspase-2 is accomplished by a caspase-3-like activity, and other ICE-like proteases less sensitive to DEVD-CHO may be responsible for activation of caspase-3 and loss of mitochondrial function.

Apoptosis↗
PubMed2003

Bcl-2 overexpression prevents daunorubicin-induced apoptosis through inhibition of XIAP and Akt degradation.

Daunorubicin (DNR) induces apoptosis in the human myeloid leukemia cells by activation of neutral sphingomyelinease and ceramide production. In the present study, we determined the effect of the antiapoptosis protein Bcl-2 on caspase-3 activation, phospholipase C-gamma 1 (PLC-gamma 1) degradation and cytochrome c release during the DNR-induced apoptosis. Treatment with 3 microM DNR for 12 hr produced morphological features of apoptosis and DNA fragmentation in U937 cells, which was associated with caspase-3 activation and PLC-gamma 1 degradation. Induction of apoptosis was also accompanied by release of cytochrome c, down-regulation of X-linked inhibitor of apoptosis protein (XIAP), and inactivation of Akt, which was blocked by the pan-caspase inhibitor z-VAD-fmk. DNR-induced caspase-3 activation, PLC-gamma 1 degradation and apoptosis were significantly attenuated in Bcl-2 overexpressing U937/Bcl-2 cells. Ectopic expression of Bcl-2 appeared to inhibit DNR-induced apoptosis by interfering with inhibition of XIAP and Akt degradation.

Antineoplastic Agents↗
PubMed2005

CD40 engagement prevents peroxisome proliferator-activated receptor gamma agonist-induced apoptosis of B lymphocytes and B lymphoma cells by an NF-kappaB-dependent mechanism.

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a transcription factor important in fat metabolism and is emerging as an important regulator of immunity and inflammation. We previously demonstrated that normal and malignant B lineage cells express PPARgamma and die by apoptosis after PPARgamma agonist exposure. In this study, we used the WEHI-231 mouse B lymphoma and normal mouse spleen B lymphocytes to elucidate the mechanism of PPARgamma agonist-induced apoptosis, and to determine whether an apoptosis rescue mechanism exists. In WEHI-231 cells, the natural PPARgamma agonist 15-deoxy-Delta(12,14)-PGJ(2) and the synthetic PPARgamma agonist ciglitazone induced activation of caspase 3 and caspase 9, a decrease in mitochondrial membrane potential, and caused cleavage of the caspase substrate poly(ADP-ribose) polymerase. We next tested whether CD40, whose engagement delivers a potent prosurvival signal for B cells, could protect B cells from PPARgamma agonist-induced apoptosis. CD40 engagement with CD40L significantly blunted the ability of PPARgamma agonists to induce apoptosis of B lymphocytes and prevented the inhibition of NF-kappaB mobilization by 15-deoxy-Delta(12,14)-PGJ(2) and ciglitazone. Interestingly, PPARgamma agonists induced an increase in IkappaBalpha and IkappaBbeta protein levels, which was prevented with CD40 engagement. The rescue mechanism induced by CD40 engagement was dependent on NF-kappaB, as an NF-kappaB inhibitor prevented rescue. Apoptosis induction by PPARgamma ligands may be important for immune regulation by killing B lymphocytes as a rapid means to dampen inflammation. Moreover, the ability of PPARgamma agonists to kill malignant B lineage cells has implications for their use as anti-B lymphoma agents.

Animals↗
PubMed2003

Staurosporine induces apoptosis in NG108-15 cells.

AIM: To observe if staurosporine induced apoptosis in NG108-15 cells and its effect on protein expression level of several genes related to apoptosis. METHODS: Phase-contrast microscopy, fluorescence microscopy, and transmission electron microscopy were used to observe staurosporine-induced morphological changes. Agarose gel electrophoresis was used to detect DNA fragmentation. Western blots were used to measure protein expression level of several genes related to apoptosis. RESULTS: Cells treated with staurosporine 0.1 micromol/L showed typical morphological changes of apoptosis. A "ladder" pattern representing fragmentation of DNA into oligonucleosome length fragments was observed after 6 h of staurosporine treatment and sustained until 24 h. The Bax expression increased significantly at 6 h after exposure to staurosporine, peaked at 12 h compared with vehicle cultures, and decreased at 24 h. The Bcl-2 expression increased and reached the highest level at 3 h. It was then decreased gradually but still higher than normal expression level. There was an obvious caspase-3 cleavage at 6 h after exposing the cells to staurosporine. Treatment with staurosporine for 12 h markedly decreased the expression of p53 protein. Cdk5 protein expression did not have obvious changes after the cells were exposed to staurosporine. CONCLUSION: Staurosporine induced apoptotic death in NG108-15 cells. Cells might die via a pathway that is dependent on Bax expression but independent of p53, and caspase-3 cleavage was involved.

Animals↗
PubMed2003

Immunohistochemical evaluation of cell proliferation antigen Ki-67 and apoptosis-related proteins Bcl-2 and caspase-3 in oral granular cell tumor.

PURPOSE: We sought to evaluate the cell proliferation activity and immunohistochemical expression of proteins that promote or inhibit apoptosis in oral granular cell tumor (GCT). STUDY DESIGN: Immunohistochemistry for Ki-67, a cell proliferation marker; Bcl-2, an anti-apoptotic protein; and caspase-3, a protein implicated in the execution of apoptosis, was performed on tissues from 12 patients with GCT of the tongue. RESULTS: Nuclear immunostaining for Ki-67 was observed only in isolated GCs (less than 2%). All patients exhibited cytoplasmic immunoreactivity for Bcl-2 in the majority of tumor cells. Cytoplasmic staining for caspase-3 was also present in more than 50% of GCs in all tumors. CONCLUSIONS: GCT cells display low proliferation activity, a finding possibly related to their benign behavior. Caspase-3 expression suggests activation of the apoptotic cascade in the GCs, but persistence of the cells in the tissues could be attributed to the expression of Bcl-2 protein, a molecule that functions as a survival factor.

Adult↗
PubMed1998

Interaction of the baculovirus anti-apoptotic protein p35 with caspases. Specificity, kinetics, and characterization of the caspase/p35 complex.

The anti-apoptotic protein p35 from baculovirus is thought to prevent the suicidal response of infected insect cells by inhibiting caspases. Ectopic expression of p35 in a number of transgenic animals or cell lines is also anti-apoptotic, giving rise to the hypothesis that the protein is a general inhibitor of caspases. We have verified this hypothesis by demonstrating that purified recombinant p35 inhibits human caspase-1, -3, -6, -7, -8, and -10 with kass values from 1.2 x 10(3) to 7 x 10(5) (M-1 s-1), and with upper limits of Ki values from 0.1 to 9 nM. Inhibition of 12 unrelated serine or cysteine proteases was insignificant, implying that p35 is a potent caspase-specific inhibitor. Mutation of the putative inhibitory loop to favor caspase-1 resulted in a substantial decline in caspase-3 inhibition, but minimal changes in caspase-1 inhibition. The interaction p35 with caspase-3, as a model of the inhibitory mechanism, revealed classic slow-binding inhibition, with both active-sites of the caspase-3 dimer acting equally and independently. Inhibition resulted from complex formation between the enzyme and inhibitor, which could be visualized under nondenaturing conditions, but was dissociated by SDS to give p35 cleaved at Asp87, the P1 residue of the inhibitor. Complex formation requires the substrate-binding cleft to be unoccupied. Taken together, these data revealed that p35 is an active-site-directed inhibitor highly adapted to inhibiting caspases.

Apoptosis↗
PubMed1999

Heat shock-induced necrosis and apoptosis in osteoblasts.

Damage to bone tissue due to heat shock is one of the main causes of the failure of osseointegration at the bone-implant interface. To investigate the effect of heat shock on regeneration of bone tissue, osteoblasts were exposed to heat shock for 10 minutes at 42, 45, or 48 degrees C or kept at 37 degrees C as a control. After 10 minutes of heat shock, disruption of actin filaments was seen in the cells and the degree of disruption increased with the temperature. The cytoskeleton reassembled after a 12-hour incubation at 37 degrees C in the cells treated at 42 or 45 degrees C, but this reversible recovery did not occur in the cells treated at 48 degrees C. Flow cytometric analysis showed that heat shock at 48 degrees C increased the number of necrotic cells to 15-20% within minutes (p < 0.05 compared with 37 degrees C). Apoptosis, evidenced by annexin V staining, DNA laddering, and caspase 3 activation, started after 6-8 hours of incubation, reached a peak at 12 hours, and gradually declined (p<0.05). Pretreatment with the antioxidant N-acetyl-L-cysteine reduced the necrosis induced at 48 degrees C of heat shock by one-half (p<0.05) but had no significant effect on caspase 3 activation induced by heat shock, suggesting that reactive oxygen species were critical in heat shock-induced necrosis but not in apoptosis. Heat shock at 48 degrees C induced a sustained translocation of p53 into the nucleus and a sustained activation of c-jun N-terminal kinase, whereas that at 42 and 45 degrees C induced only transient p53 translocation and c-jun N-terminal kinase activation. These results suggest that the sustained activation of p53 and c-jun N-terminal kinase pathways may contribute to heat shock-induced apoptosis. On the other hand, heat shock protein 70 increased dramatically in the cells treated at 45 or 48 degrees C, suggesting that the protecting mechanism in the cells was also activated. Such protection was able to prevent apoptosis in cells treated at 45 degrees C but not in those treated at 48 degrees C.

Actins↗
PubMed2000

Nuclear factor-kappaB and caspases co-operatively regulate the activation and apoptosis of human macrophages.

Accumulating evidence suggests that macrophages function as major effector cells in the pathological process of various human diseases. We examined here the role of nuclear factor-kappaB (NF-kappaB) and caspases in the regulation of activation and apoptosis of macrophages. Activation of the human monoblastic leukaemia cell line, U937, by phorbol 12-myristate 13-acetate (PMA) increased the expression of CD14/CD86, and cytokine production. PMA stimulation also increased the expression of both pro-caspase-8 and pro-caspase-3 in U937, but not apoptosis or intracellular caspase-3 activity. PMA also increased the expression of X-chromosome-linked inhibitor of apoptosis protein (XIAP) in U937, suggesting an inhibitory action for XIAP on the caspase cascade in PMA-stimulated U937. Electrophoretic mobility shift assay (EMSA) showed a significant increase of nuclear NF-kappaB activity in PMA-stimulated U937. When a potent NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC), was added to U937 cell culture in the presence of PMA, apoptosis was triggered by activation of caspase-3, which was induced by caspase-8 activation. XIAP expression was markedly suppressed in PMA-treated U937 in the presence of PDTC. The inhibitors of caspase-8 and caspase-3 mostly inhibited apoptosis of U937 treated with PMA in the presence of PDTC. Furthermore, a phenotype of U937 treated with PMA and PDTC in the presence of caspase inhibitor was almost identical to that of unstimulated U937. Our results suggest that the signalling pathways involved in the activation and apoptosis of human macrophages could be co-operatively regulated by the use of NF-kappaB and caspase inhibitors, thus enabling the control of macrophage function and number.

Apoptosis↗
PubMed2004

Aloe-emodin induced in vitro G2/M arrest of cell cycle in human promyelocytic leukemia HL-60 cells.

In this study, we have evaluated the chemopreventive role of aloe-emodin in human promyelocytic leukemia HL-60 cells in vitro by studying the regulation of proliferation, cell cycle and apoptosis. Aloe-emodin inhibited cell proliferation and induced G2/M arrest and apoptosis in HL-60 cells. Investigation of the levels of cyclins B1, E and A by immunoblot analysis showed that cyclin E level was unaffected, whereas cyclin B1 and A levels increased with aloe-emodin in HL-60 cells. Investigation of the levels of cyclin-dependent kinases, Cdk1 and 2, showed increased levels of Cdk1 but the levels of Cdk2 were not effected with aloe-emodin in HL-60 cells. The levels of p27 were increased after HL-60 cells were cotreated with various concentrations of aloe-emodin. The increase of the levels of p27 may be the major factor for aloe-emodin to cause G2/M arrest in these examined cells. Flow cytometric assays and DNA fragmentation gel electrophoresis also confirmed aloe-emodin induced apoptosis in HL-60 cells. The levels of caspase-3 were increased after HL-60 cells were cotreated with 10 microM aloe-emodin for 12, 24, 48, and 72 hours. Taken together, aloe-emodin therefore appears to exert its anticarcinogenesis properties by inhibiting proliferation and inducing cell cycle arrest and apoptosis underwent activation of caspase-3 in human leukemia HL-60 cells.

Anthraquinones↗
PubMed2006

Inhibition of 12-lipoxygenase during baicalein-induced human lung nonsmall carcinoma H460 cell apoptosis.

Baicalein is known as a 12-lipoxygenase (12-LOX) inhibitor. The 12-LOX is found to be involved in the progression of human cancers and the inhibitor of 12-LOX offers a target for the prevention cancer. We demonstrated the inhibitory effect of baicalein on the gene and protein expression of 12-LOX in H460 human lung nonsmall carcinoma cell line. Treatment of baicalein inhibited the growth of H460 cells in a dose-dependent manner. Following 24h exposure to 50muM baicalein, cell cycle analysis revealed an increase in the cell population in S-phase. During the S-phase arrest, baicalein decreased the protein levels of cdk1 and cyclin B1, which are the regulating proteins of S-phase transition to G2/M-phase, in this study. Furthermore, baicalein induced the most of H460 cell apoptosis after treatment for 48h. H460 cells formed vesicles and apoptotic body, and then floated after treatment with baicalein. Baicalein-induced H460 cell apoptosis was confirmed by DNA condensation and fragmentation. Baicalein-induced apoptosis were also accompanied by decreasing in Bcl-2 and proform of caspase-3 and increasing p53 and Bax protein levels. Pretreatment with a specific caspase-3 inhibitor, Ac-DEVD-CHO, partially reduced baicalein-induced cell death, indicating baicalein induces apoptosis is partially dependent on caspase-3 pathway in H460 cells. These data suggest that baicalein, a 12-LOX inhibitor, inhibits the proliferation of H460 cells via S-phase arrest and induces apoptosis in association with the regulation of molecules in the cell cycle and apoptosis-related proteins.

Antineoplastic Agents, Phytogenic↗
PubMed2003

An antisense plasmid targeting survivin expression induces apoptosis and sensitizes hepatocarcinoma cells to chemotherapy.

To explore the change of sensitivity to chemotherapy of antisense RNA targeting survivin on hepatocarcinoma carcinoma cells in vitro. Survivin mRNA structure region was amplified by RT-PCR and inserted inversely into eukaryotic expression vector pcDNA3. The antisense expression plasmid pcDNA3/survivin was transfected into HepG2 with lipofectAMINE 2000 (LF2000), with low concentration of 5-fluorouracil (5-Fu) added. Survivin protein was detected by Western-blot, the growth activity was measured by MTT, and apoptosis was detected by Flow Cytometry 12 h, 24 h, 48 h after transfection. The activity of caspase-3 was found by quantitative assay 48 h after transfection. The construction of antisense RNA vector pcDNA3/survivin was verified by restricted endonuclease digestion and nucleotide sequencing. Compared with normal group, 5-Fu and antisense survivin group, the cells growth inhibition, apoptosis index, and caspase-3 activity were increased in antisense survivin transfected + 5-Fu group. The threshold of apoptosis was decreased after survivin was silenced, and the sensitivity to chemotherapy was increased. These findings suggest the existence of a potential new target for gene therapy.

Antigens, Neoplasm↗
PubMed2001

Endothelial cell death and decreased expression of vascular endothelial growth factor and vascular endothelial growth factor receptor 2 in emphysema.

Emphysema due to cigarette smoking is characterized by a loss of alveolar structures. We hypothesize that the disappearance of alveoli involves apoptosis of septal endothelial cells and a decreased expression of lung vascular endothelial growth factor (VEGF) and its receptor 2 (VEGF R2). By terminal transferase dUTP nick end labeling (TUNEL) in combination with immunohistochemistry, we found that the number of TUNEL+ septal epithelial and endothelial cells/lung tissue nucleic acid (microg) was increased in the alveolar septa of emphysema lungs (14.2 +/- 2.0/microg, n = 6) when compared with normal lungs (6.8 +/- 1.3/microg, n = 7) (p < 0.01) and with primary pulmonary hypertensive lungs (2.3 +/- 0.8/microg, n = 5) (p < 0.001). The cell death events were not significantly different between healthy nonsmoker (7.4 +/- 1.9/microg) and smoker (5.7 +/- 0.7/microg) control subjects. The TUNEL results were confirmed by single-stranded DNA and active caspase-3 immunohistochemistry, and by DNA ligation assay. Emphysema lungs (n = 12) had increased levels of oligonucleosomal-length DNA fragmentation when compared with normal lungs (n = 11). VEGF, VEGF R2 protein, and mRNA expression were significantly reduced in emphysema. We propose that epithelial and endothelial alveolar septal death due to a decrease of endothelial cell maintenance factors may be part of the pathogenesis of emphysema.

Adolescent↗
PubMedDate not supplied

Regulation of apoptosis through arachidonate cascade in mammalian cells.

The arachidonate cascade includes the cyclooxygenase (COX) pathway to form prostanoids and the lipoxygenase (LOX) pathway to generate several oxygenated fatty acids, collectively called eicosanoids. Eicosanoids are suggested to play a dual role in regulating cell survival and apoptosis in various types of cells through an unknown mechanism. We found apoptosis in cultured Madin-Darby canine kidney (MDCK) cells treated with 12-O-tetradecanoylphorbol beta-acetate (TPA), a potent tumor promoter, and nordihydroguaiaretic acid (NDGA), a LOX inhibitor. The effect of TPA was synergistically stimulated along with NDGA. Aspirin, a COX inhibitor, was not effective. The target of NDGA might be different from the mechanism involving a LOX activity in some kinds of carcinoma cells because the increased expression of 12-LOX was not detected in MDCK cells treated with TPA. Caspase and poly(ADP-ribose) metabolites were found to be involved in the signal transduction pathway of the TPA- and NDGA-induced apoptosis in MDCK cells. Alternatively, hydrogen peroxide-induced apoptosis was not affected by NDGA. Thus, the TPA-induced response involved the mechanism independent of the oxidative stress. Obesity is a risk factor for severe diseases including noninsulin-dependent diabetes and atherosclerosis characterized by the changes of cell properties of adipocytes. We found that conjugated linolenic acid from bitter gourd was able to induce apoptosis in mouse preadipogenic 3T3-L1 cells. The findings provide the potential use of conjugated fatty acids to regulate obesity.

3T3 Cells↗
PubMed2004

Role of tumor necrosis factor-alpha in the development of spontaneous hepatic toxicity in Long-Evans Cinnamon rats.

The objective of this study was to evaluate the potential role of TNF-alpha in the onset of acute hepatitis in the Long-Evans Cinnamon (LEC) rat, an animal model for inherited copper (Cu) toxicosis. In LEC rats, Cu is accumulated in the liver with age, and clinical signs of acute hepatitis were observed as, icterus, reduced body weight, nasal bleeding, dehydration, and reduced food intake at 12 weeks of age. Cellular changes such as apoptosis in the liver were evident in these rats with increasing age. Positive TNF-alpha and TNFR1 immunostainings were observed in hepatocytes and Kupffer cells in LEC rats. Hepatic levels of caspase-3 activity, TNF-alpha mRNA, and protein were also increased in LEC rats from 6 to 12 weeks of age as compared with control Long-Evans (LE) rats. The neutralization of TNF-alpha by passive immunization or the inhibition of caspase activity can block the apoptotic process initiated by TNF-alpha. In this study, we evaluated the effects of passive immunization of LEC rats with weekly administration of anti-rat TNF-alpha on Cu-induced acute hepatitis. This treatment resulted in a reduction of the percentage of apoptotic cells in the liver, decreased activity of caspase-3, and also in down-regulation of the TNF-alpha gene expression. Thus, these results suggest a major role for TNF-alpha on the pathogenesis of Cu-induced acute hepatitis in LEC rats.

Alanine Transaminase↗
PubMed2006

CARD15 single nucleotide polymorphisms 8, 12 and 13 are not increased in ethnic Danes with sarcoidosis.

BACKGROUND: Mutations of the caspase-activating recruitment domain 15 (CARD15) gene on chromosome 16 are associated with chronic inflammatory granulomatous bowel disease (Crohn's disease). Sarcoidosis is a systemic granulomatous disease with unknown etiology, which shares histological features with Crohn's disease. OBJECTIVES: To evaluate whether ethnic Danes with sarcoidosis have an increased frequency of CARD15 mutations compared to healthy control subjects. METHODS: Genotyping for CARD15 mutations R702W, G908R, and L1007fsinsC, also designated single nucleotide polymorphism (SNP) SNP8, SNP12 and SNP13, respectively, were performed by capillary electrophoresis single-strand confirmation polymorphism in 53 patients with histologically verified sarcoidosis and in 103 healthy controls. RESULTS: The frequencies of CARD15 mutations in sarcoidosis patients were: SNP8, 4/106 chromosomes (3.8%); SNP12, 2/106 chromosomes (1.9%); SNP13, 2/106 chromosomes (1.9%); SNP8+SNP12+SNP13, 8/106 chromosomes (7.6%). All 8 patients were heterozygous. The frequencies in controls were: SNP8, 9/206 chromosomes (4.4%); SNP12, 2/206 chromosomes (1.0%); SNP13, 4/206 chromosomes (1.9%); SNP8+SNP12+SNP13, 15/206 chromosomes (7.3%). All controls were heterozygous. The differences were not statistically significant (p>0.05). Furthermore, the course of disease was not significantly different in the 8 patients with CARD15 mutations and the 45 patients without mutations. CONCLUSION: The frequency of CARD15 mutations is not increased in ethnic Danish patients with sarcoidosis, and heterozygosity for such mutations apparently has no influence on the course of disease.

Adult↗