Biomedical subjects

J Cai

Publications and source records attributed to J Cai.

At least 181 records · Page 10Linked to original sources

PubMed1998

Gap junctional communication and the tyrosine phosphorylation of connexin 43 in interaction between breast cancer and endothelial cells.

Abnormal gap junction communication (GJC) has been associated with carcinogenesis. We investigated the role of endothelial cell GJC and connexin 43 (Cx43), the main gap junction protein in these cells, during tumour cell extravasation. GJC was determined by the ability of cells to transfer Lucifer yellow, to neighbouring cells. Tumour-endothelial interaction was assessed by DiI assay. Connexin 43 expression and tyrosine phosphorylation were measured by immunoprecipitation and Western blotting. Co-culturing of ECV304 endothelial cells with human breast cancer cells resulted in a rapid and transient loss of communication competence of ECV304. This inhibition was maximal within 5 min. GJC was almost fully restored in 2 h. The co-culturing also resulted in an increase in the tyrosine phosphorylation of CX43. The pattern of phosphorylation was similar to the loss and the recovery of GJC in ECV304. We conclude that interaction of tumour cells with endothelium effectively inhibits GJC of endothelial cells, which is attributed to the increased tyrosine phosphorylation of connexin 43. This may contribute to the extravasation of tumour cells from the circulation, an essential step in the establishment of metastasis.

Adenocarcinoma↗

PubMed1997

Boron-containing polyamines as DNA targeting agents for neutron capture therapy of brain tumors: synthesis and biological evaluation.

Three series of new boron-containing spermidine/spermine (SPD/SPM) analogues have been synthesized: N1- and N5-(4-carboranylbutyl) SPD/SPM derivatives (SPD-1, SPD-5, SPM-1, SPM-5); N1,N10-diethyl-N5-(4-carboranylbutyl)spermidine (DESPD-5), N1,N14-diethyl-N5-(4-carboranylbutyl)spermine (DESPM-5); and N5,N10-bis(4-carboranylbutyl)spermine (SPM-5,10). In vitro studies using rat F98 glioma cells have shown that these polyamines retain the ability to displace ethidium bromide from calf thymus DNA and are rapidly taken up by F98 glioma cells. However, their cytotoxicities, especially those with terminal N-substituted (SPD-1, SPM-1) boron compounds, are greater than those of SPD/SPM. Nevertheless, the groundwork has been created for a new class of boron-containing compounds that maybe useful for boron neutron capture therapy of tumors.

Animals↗

PubMed1997

Elevations in cathepsin B protein content and enzyme activity occur independently of glycosylation during colorectal tumor progression.

Western blots, enzyme assays, protein glycosylation studies, and immunohistochemical staining were used to characterize cathepsin B expression at successive stages of colorectal tumor progression. In normal colon mucosa and premalignant adenomas, cathepsin B expression was predominantly due to mature two-chain protein detected on Western blots as the nonglycosylated 27-kDa form, with overexpression of this protein occurring in only 4 of 18 adenomas. Overexpression increased significantly in Dukes A and B carcinomas (26 of 37 cases), with cathepsin B protein generally detectable in carcinomas as a combination of both 27-kDa nonglycosylated and 28-kDa glycosylated mature two-chain forms. Glycosylated cathepsin B protein in carcinoma extracts was sensitive to PNGase F but resistant to Endo H, indicating a pattern consistent with complex rather than high mannose type glycosylation. When sorted by advancing tumor stage, peak expression of cathepsin B protein occurred in carcinomas involved in local invasion compared with adenomas or metastatic cancers. At all stages, cathepsin B activity correlated significantly with the levels of heavy chain mature cathepsin B protein (r = 0.6682, p < 0.0001) irrespective of glycosylation. Immunohistochemical staining of cathepsin B protein revealed fine diffuse cytoplasmic staining in both adenomas and carcinomas compared with coarse granular cytoplasmic staining (typical of lysosomes) seen in matched normal mucosa. Our results demonstrate several sequential, apparently independent changes in cathepsin B expression during colorectal tumor progression including early changes in subcellular localization, up-regulation of cathepsin B protein and activity in invasive cancers, and altered protein glycosylation detected in malignant tumors at all stages.

Adenoma↗

PubMed1997

Estimating the mean hazard ratio parameters for clustered survival data with random clusters.

We consider a latent variable hazard model for clustered survival data where clusters are a random sample from an underlying population. We allow interactions between the random cluster effect and covariates. We use a maximum pseudo-likelihood estimator to estimate the mean hazard ratio parameters. We propose a bootstrap sampling scheme to obtain an estimate of the variance of the proposed estimator. Application of this method in large multi-centre clinical trials allows one to assess the mean treatment effect, where we consider participating centres as a random sample from an underlying population. We evaluate properties of the proposed estimators via extensive simulation studies. A real data example from the Studies of Left Ventricular Dysfunction (SOLVD) Prevention Trial illustrates the method.

Adult↗

PubMed1997

Vascular MADs: two novel MAD-related genes selectively inducible by flow in human vascular endothelium.

Vascular endothelium is an important transducer and integrator of both humoral and biomechanical stimuli within the cardiovascular system. Utilizing a differential display approach, we have identified two genes, Smad6 and Smad7, encoding members of the MAD-related family of molecules, selectively induced in cultured human vascular endothelial cells by steady laminar shear stress, a physiologic fluid mechanical stimulus. MAD-related proteins are a recently identified family of intracellular proteins that are thought to be essential components in the signaling pathways of the serine/threonine kinase receptors of the transforming growth factor beta superfamily. Smad6 and Smad7 possess unique structural features (compared with previously described MADs), and they can physically interact with each other, and, in the case of Smad6, with other known human MAD species, in endothelial cells. Transient expression of Smad6 or Smad7 in vascular endothelial cells inhibits the activation of a transfected reporter gene in response to both TGF-beta and fluid mechanical stimulation. Both Smad6 and Smad7 exhibit a selective pattern of expression in human vascular endothelium in vivo as detected by immunohistochemistry and in situ hybridization. Thus, Smad6 and Smad7 constitute a novel class of MAD-related proteins, termed vascular MADs, that are induced by fluid mechanical forces and can modulate gene expression in response to both humoral and biomechanical stimulation in vascular endothelium.

Amino Acid Sequence↗

PubMed1997

Differential regulation of gamma-glutamylcysteine synthetase heavy and light subunit gene expression.

gamma-Glutamylcysteine synthetase (GCS) is the rate-limiting enzyme in the biosynthesis of glutathione and is composed of a heavy and a light subunit. Although the heavy subunit is enzymically active alone, the light subunit plays an important regulatory role by making the holoenzyme function more efficiently. In the current study we examined whether conditions which are known to influence gene expression of the heavy subunit also influence that of the light subunit, and the mechanisms involved. Treatment of cultured rat hepatocytes with hormones such as insulin and hydrocortisone, or plating hepatocytes under low cell density increased the steady-state mRNA level of the heavy subunit only. Treatment with diethyl maleate (DEM), buthionine sulphoximine (BSO) and t-butylhydroquinone (TBH) increased the steady state mRNA level and gene transcription rates of both subunits. These treatments share in common their ability to induce oxidative stress and activate nuclear factor kappa B (NF-kappa B). Treatment with protease inhibitors 7-amino-1-chloro-3-tosylamido-2-heptanone (TLCK) or L-1-tosylamido-2-phenylethyl chloromethyl ketone (TPCK) had no influence on the basal NF-kappa B and GCS subunit mRNA levels, but blocked the activation of NF-kappa B by DEM, BSO and TBH, and the increase in GCS heavy subunit mRNA level by BSO and TBH. On the other hand, the DEM-, BSO- and TBH-induced increase in GCS light-subunit mRNA level was unaffected by TLCK and TPCK. Thus only the heavy subunit is hormonally regulated and growth sensitive, whereas both subunits are regulated by oxidative stress. Signalling through NF-kappa B is involved only in the oxidative-stress-mediated changes in the heavy subunit gene expression.

Animals↗

PubMed1997

Interleukin 6 and interferon-gamma gene expression in lung transplant recipients with refractory acute cellular rejection: implications for monitoring and inhibition by treatment with aerosolized cyclosporine.

BACKGROUND: The purpose of this study was to correlate cytokine gene expression from bronchoalveolar lavage (BAL) cells and peripheral blood lymphocytes (PBL) with graft histology in recipients with persistent acute rejection treated with aerosolized cyclosporine (ACsA). METHODS: We measured mRNA for interleukin (IL) 6, interferon (IFN)-gamma, and IL-10 in recipients (1) without rejection (n=13), (2) with acute rejection that responded to pulsed methylprednisolone (n=7), and (3) with "refractory" acute rejection that failed to respond to conventional immunosuppression (n=17). In the latter group, ACsA was initiated. RESULTS: BAL cell IL-6 and IFN-gamma were highest in recipients with refractory rejection compared with recipients with steroid-responsive rejection and recipients with no rejection. Improvement in rejection histology occurred in 15 of 17 recipients who were treated with ACsA. IL-6 and IFN-gamma mRNA levels from BAL cells decreased during treatment with ACsA (median IL-6:actin ratio: before treatment, 0.40 vs. after treatment, 0.003, P=0.001; IFN-gamma:actin ratio: before treatment, 0.32 vs. after treatment, 0.04, P=0.001). PBL IL-6 and IFN-gamma mRNA expression also decreased during ACsA treatment after 180 days. Expression of IL-10 mRNA from BAL and PBL did not change during ACsA treatment (0.0 vs. 0.03 and 0.0 vs. 0.02, respectively). CONCLUSIONS: IL-6 and IFN-gamma mRNA expression from BAL cells was highest in those recipients with refractory histologic acute rejection. ACsA was associated with decreased IFN-gamma and IL-6 gene expression in BAL cells and PBL.

Acute Disease↗

PubMed1997

A complex consisting of human replication factor C p40, p37, and p36 subunits is a DNA-dependent ATPase and an intermediate in the assembly of the holoenzyme.

Human replication factor C (hRFC) is a multi-subunit protein complex capable of supporting proliferating cell nuclear antigen (PCNA)-dependent DNA synthesis by DNA polymerases delta and epsilon. The hRFC complex consists of five different subunits with apparent molecular masses of 140, 40, 38, 37, and 36 kDa. We have previously reported the expression of a three-subunit core complex, consisting of the p40, p37, and p36 subunits following coupled in vitro transcription-translation of the cDNAs encoding these proteins (Uhlmann, F., Cai, J., Flores-Rozas, H., Dean, F. B., Finkelstein, J. , O'Donnell, M., and Hurwitz, J. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 6521-6526). Here we describe the isolation of a stable complex composed of the p40, p37, and p36 subunits of hRFC from baculovirus-infected insect cells. The purified p40.p37.p36 complex, like the five-subunit RFC, contained DNA-dependent ATPase activity that was stimulated by PCNA, preferentially bound to primed DNA templates, interacted with PCNA, and was capable of unloading PCNA from singly-nicked circular DNA. In contrast to the five-subunit RFC, the three-subunit core complex did not load PCNA onto DNA. The p40. p37.p36 complex inhibited the elongation of primed DNA templates catalyzed by the DNA polymerase delta holoenzyme. Incubation of the p40.p37.p36 complex with the hRFC p140 and p38 subunits formed the five-subunit hRFC complex that supported PCNA-dependent DNA synthesis by DNA polymerase delta.

Adenosine Triphosphatases↗

PubMed1997

Exposure of infants to phyto-oestrogens from soy-based infant formula.

BACKGROUND: The isoflavones genistein, daidzein, and their glycosides, found in high concentrations in soybeans and soy-protein foods, may have beneficial effects in the prevention or treatment of many hormone-dependent diseases. Because these bioactive phyto-oestrogens possess a wide range of hormonal and non-hormonal activities, it has been suggested that adverse effects may occur in infants fed soy-based formulas. METHODS: To evaluate the extent of infant exposure to phyto-oestrogens from soy formula, the isoflavone composition of 25 randomly selected samples from five major brands of commercially available soy-based infant formulas were analysed, and the plasma concentrations of genistein and daidzein, and the intestinally derived metabolite, equol, were compared in 4-month-old infants fed exclusively soy-based infant formula (n = 7), cow-milk formula (n = 7), or human breast-milk (n = 7). FINDINGS: All of the soy formulas contained mainly glycosides of genistein and daidzein, and the total isoflavone content was similar among the five formulas analysed and was related to the proportion of soy isolate used in their manufacture. From the concentrations of isoflavones in these formulas (means 32-47 micrograms/mL), the typical daily volume of milk consumed, and average bodyweight, a 4-month-old infant fed soy formula would be exposed to 28-47 per day, or about 4.5-8.0 mg/kg bodyweight per day, of total isoflavones. Mean (SD) plasma concentrations of genistein and daidzein in the seven infants fed soy-based formulas were 684 (443) ng/mL and 295 (60) ng/mL, respectively, which was significantly greater (p < 0.05) than in the infants fed either cow-milk formulas (3.2 [0.7] and 2.1 [0.3] ng/mL), or human breast-milk (2.8 [0.7] and 1.4 [0.1] ng/mL), and an order of magnitude higher per bodyweight than typical plasma concentrations of adults consuming soy foods. INTERPRETATION: The daily exposure of infants to isoflavones in soy infant-formulas is 6-11 fold higher on a bodyweight basis than the dose that has hormonal effects in adults consuming soy foods. Circulating concentrations of isoflavones in the seven infants fed soy-based formula were 13000-22000 times higher than plasma oestradiol concentrations in early life, and may be sufficient to exert biological effects, whereas the contribution of isoflavones from breast-milk and cow-milk is negligible.

Animals↗

PubMed1997

The MAD-related protein Smad7 associates with the TGFbeta receptor and functions as an antagonist of TGFbeta signaling.

TGFbeta signaling is initiated when the type I receptor phosphorylates the MAD-related protein, Smad2, on C-terminal serine residues. This leads to Smad2 association with Smad4, translocation to the nucleus, and regulation of transcriptional responses. Here we demonstrate that Smad7 is an inhibitor of TGFbeta signaling. Smad7 prevents TGFbeta-dependent formation of Smad2/Smad4 complexes and inhibits the nuclear accumulation of Smad2. Smad7 interacts stably with the activated TGFbeta type I receptor, thereby blocking the association, phosphorylation, and activation of Smad2. Furthermore, mutations in Smad7 that interfere with receptor binding disrupt its inhibitory activity. These studies thus define a novel function for MAD-related proteins as intracellular antagonists of the type I kinase domain of TGFbeta family receptors.

Amino Acid Sequence↗

PubMed1997

Expression of the bumetanide-sensitive Na-K-Cl cotransporter BSC2 is differentially regulated by fluid mechanical and inflammatory cytokine stimuli in vascular endothelium.

In vascular endothelium, the electroneutral Na-K-Cl cotransport system is thought to function in the maintenance of a selective permeability barrier in certain vascular beds (e.g., brain), as well as in the preservation of endothelial homeostasis in the face of fluctuating osmotic conditions that may accompany certain pathophysiological conditions (e.g., diabetes mellitus). Here we demonstrate that the gene encoding the bumetanide-sensitive cotransporter BSC2, one of the two major isoforms of Na-K-Cl cotransporters present in mammalian cells, can be differentially regulated by inflammatory cytokines and fluid mechanical forces in cultured endothelium. Interleukin-1beta and tumor necrosis factor-alpha significantly upregulate expression of BSC2 mRNA and protein in human umbilical vein endothelial cells, a response that is inhibited by pretreatment with interferon-gamma. Steady laminar fluid shear stress, at a physiologic magnitude (10 dyn/cm2), is also able to induce and maintain elevated expression of BSC2 in cultured human umbilical vein endothelial cells, while a comparable time-averaged magnitude of turbulent fluid shear stress is not. In vivo, BSC2 mRNA is upregulated after intraperitoneal administration of bacterial endotoxin (LPS) in murine lung and kidney, but not in cardiac tissue. These results provide the first experimental evidence that the BSC2 gene can be selectively regulated by different inflammatory cytokine and fluid mechanical stimuli in endothelium, and support a role for BSC2 in vascular homeostasis and inflammation.

Animals↗

PubMed1997

N-ras protein: frequent quantitative and qualitative changes occur in human colorectal carcinomas.

Point mutation and overexpression are recognized mechanisms for ras activation in malignancy. However, little information is available on overexpression of N-ras protein compared with H- or K-ras proteins, as N-ras-specific antibodies have only recently become available. For comparative analyses of ras protein levels, we have probed Western blots of extracts from 9 normal human tissues and 55 pairs of colorectal carcinoma and matched control mucosa, using monoclonal antibodies (MAbs) specific for H-, K- or N-ras proteins. On multi-tissue blots, N-ras protein was more highly expressed in colon than in the other human tissues analyzed, suggesting a role for N-ras in colorectal function. N-ras protein levels in multiple independent extracts of normal colon mucosa were consistently higher than either K-ras protein or H-ras protein levels. In 69% of colon carcinomas, N-ras protein levels were increased an average of 4.8-fold over normal mucosa. Overexpression of K-ras protein was also observed in colon cancers but less frequently (13% of cases) than N-ras protein. H-ras protein levels were too low for comparative studies. Alterations in N-ras protein mobility, possibly reflecting increased post-translational processing, were also detected in 42% of colon carcinomas. N-ras protein, typically present as a single 23 kDa band in normal mucosa, was expressed in some cancers as a 22 kDa band or as multiple bands of 20-23 kDa. Sequencing of N-ras DNA from 6 carcinomas with these variations in protein mobility did not reveal mutations in codons 12, 13, 59 or 61. Thus, frequent quantitative and qualitative changes in N-ras protein expression, which do not appear to correlate with the presence of typical N-ras point mutations, result in abnormal N-ras protein patterns in human colorectal carcinomas.

Antibodies, Monoclonal↗

PubMed1997

Cardiac autonomic function and incident coronary heart disease: a population-based case-cohort study. The ARIC Study. Atherosclerosis Risk in Communities Study.

Cardiac autonomic activity, as assessed by heart rate variability, has been found to be associated with postmyocardial infarction mortality, sudden death, and all-cause mortality. However, the association of heart rate variability and the incidence of coronary heart disease (CHD) is not well described. The authors report on the association of baseline cardiac autonomic activity (1987-1989) with incident CHD after 3 years (1990-1992) of follow-up of the Atherosclerosis Risk in Communities Study cohort selected from four study centers in the United States by using a case-cohort design. The authors examined 137 incident cases of CHD and a stratified random sample of 2,252 examinees free of CHD at baseline. Baseline, supine, resting beat-to-beat heart rate data were collected. High- (0.16-0.35 Hz) and low- (0.025-0.15 Hz) frequency spectral powers and high-/low-frequency power ratio, estimated from spectral analysis, and standard deviation of all normal R-R intervals, calculated from time domain analysis, were used as the conventional indices of cardiac parasympathetic, sympatho-parasympathetic, and their balance, respectively. Incident CHD was defined as hospitalized myocardial infarction, fatal CHD, or cardiac revascularization procedures during 3 years of follow-up. The age, race, gender, and other CHD risk factor-adjusted relative risks (and 95% confidence intervals) of incident CHD comparing the lowest quartile with the upper three quartiles of high-frequency power, low-frequency power, high-/low-frequency power ratio, and standard deviation of R-R intervals were 1.72 (95% confidence interval (CI) 1.17-2.51), 1.09 (95% CI 0.72-1.64), 1.25 (95% CI 0.84-1.86), and 1.39 (95% CI 0.94-2.04), respectively. The findings from this population-based, prospective study suggest that altered cardiac autonomic activity, especially lower parasympathetic activity, is associated with the risk of developing CHD.

Case-Control Studies↗

PubMed1997

Quantitative multi-residue determination of beta-agonists in bovine urine using on-line immunoaffinity extraction-coupled column packed capillary liquid chromatography-tandem mass spectrometry.

This report demonstrates the potential of on-line immunoaffinity extraction and coupled column packed capillary liquid chromatography-ion spray tandem mass spectrometry for multi-residue determination of five beta-agonists, clenbuterol, mabuterol, mapenterol, methylclenbuterol, and tolubuterol, in bovine urine using an automated column switching system. Trace enrichment and preliminary sample cleanup was performed on-line using bovine urine diluted with phosphate-buffered saline. The column switching process involves trapping the target analytes onto a mini-bore immunoaffinity column, whereupon the target analytes are released from the immunoaffinity column onto a trapping column and subsequently eluted onto a packed capillary analytical column. The latter packed capillary column was used to provide the optimum sensitivity for ion spray LC-MS-MS analyses. The three-column system consists of a 2.0 mm I.D. immunoaffinity column, a 1 mm I.D. reversed-phase trapping column and a 320 microm I.D. packed capillary analytical column. Both qualitative and quantitative results are presented for the multi-residue determination of the target beta-agonists from the complex urinary matrix. Using tolubuterol as an internal standard, the quantitative data showed good linear response within the concentration ranges studied. Lower levels of quantitation were 50 part per trillion (ppt) for clenbuterol and methylclenbuterol, 20 ppt for mabuterol and 10 ppt for mapenterol. The bovine renal elimination is described using the technique for one of the beta-agonists, clenbuterol. The concentration of clenbuterol was detectable 15 days after the cessation of oral administration.

Adrenergic beta-Agonists↗

PubMed1997

Deletion analysis of the large subunit p140 in human replication factor C reveals regions required for complex formation and replication activities.

Replication factor C (RFC) and proliferating cell nuclear antigen (PCNA) are processivity factors for eukaryotic DNA polymerases delta and epsilon. RFC contains multiple activities, including its ability to recognize and bind to a DNA primer end and load the ring-shaped PCNA onto DNA in an ATP-dependent reaction. PCNA then tethers the polymerase to the template allowing processive DNA chain elongation. Human RFC consists of five distinct subunits (p140, p40, p38, p37, and p36), and RFC activity can be reconstituted from the five cloned gene products. To characterize the role of the large subunit p140 in the function of the RFC complex, deletion mutants were created that defined a region within the p140 C terminus required for complex formation with the four small subunits. Deletion of the p140 N-terminal half, including the DNA ligase homology domain, resulted in the formation of an RFC complex with enhanced activity in replication and PCNA loading. Deletion of additional N-terminal amino acids, including those constituting the RFC homology box II that is conserved among all five RFC subunits, disrupted RFC replication function. DNA primer end recognition and PCNA binding activities, located in the p140 C-terminal half, were unaffected in this mutant, but PCNA loading was abolished.

DNA↗

PubMed1997

Identification of regions within the four small subunits of human replication factor C required for complex formation and DNA replication.

Replication factor C (RFC) and proliferating cell nuclear antigen (PCNA) are processivity factors for eukaryotic DNA polymerases delta and epsilon. RFC binds to a DNA primer end and loads PCNA onto DNA in an ATP-dependent reaction. The five RFC subunits p140, p40, p38, p37, and p36, all of which are required to form the active RFC complex, share regions of high homology including the defined RFC boxes II-VIII. RFC boxes III and V constitute a putative ATP binding site, whereas the function of the other conserved boxes is unknown. To study the individual subunits in the RFC complex and the role of the RFC boxes, deletion mutations were created in all subunits. Sequences close to the C terminus of each of the small subunits are required for formation of the five subunit complex. A N-terminal region of the small subunits, containing the RFC homology box II, plays a critical role in the function of these subunits, deletion of which reduces but does not abolish RFC activity in loading PCNA onto DNA and in supporting an RFC-dependent replication reaction. The N termini of p37 and p40, although highly homologous, are not interchangeable, suggesting unique functions for the individual subunits.

DNA Repair↗

PubMed1997

Glucocorticoids induce Kaposi's sarcoma cell proliferation through the regulation of transforming growth factor-beta.

Glucocorticoid (GC) use is known to induce or enhance the growth of Kaposi's sarcoma (KS) in many clinical settings including human immunodeficiency virus infection, collagen vascular disease, lymphoproliferative disorders, and renal transplantation. Because GCs may induce immune suppression and thus tumor growth, we determined whether GCs had a direct effect on KS growth. We found that GCs directly induce the growth of KS cell lines. In examining the mechanism of action of GCs, we did not observe induction of known autocrine growth factors for KS including interleukin-1 (IL-1), IL-6, oncostatin-M, basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF). We thus examined factor(s) that inhibit KS growth. Transforming growth factor-beta (TGF-beta) is produced by KS cells and has pleiotropic effects, including inhibiting the growth of hematopoietic and endothelial cells. We show that TGF-beta is produced by KS cells in both the latent and active forms, and that TGF-beta is an autocrine growth inhibitory factor. We then studied the effects of GCs on the regulation of TGF-beta and found that GCs do not inhibit TGF-beta transcription, but significantly inhibit TGF-beta activation. This effect is mediated through regulation of the TGF-beta activation pathway. TGF-beta is activated by plasmin which is positively regulated by plasminogen activator (PA) and PA receptor (PAR), and negatively regulated by plasminogen activator inhibitor (PAI). GCs downregulated PAR and upregulated PAI. Thus, glucocorticoids enhance KS cell growth through the regulation of TGF-beta activation.

Cell Division↗

PubMed1997

Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked.

Bcl-2 is an integral membrane protein located mainly on the outer membrane of mitochondria. Overexpression of Bcl-2 prevents cells from undergoing apoptosis in response to a variety of stimuli. Cytosolic cytochrome c is necessary for the initiation of the apoptotic program, suggesting a possible connection between Bcl-2 and cytochrome c, which is normally located in the mitochondrial intermembrane space. Cells undergoing apoptosis were found to have an elevation of cytochrome c in the cytosol and a corresponding decrease in the mitochondria. Overexpression of Bcl-2 prevented the efflux of cytochrome c from the mitochondria and the initiation of apoptosis. Thus, one possible role of Bcl-2 in prevention of apoptosis is to block cytochrome c release from mitochondria.

Apoproteins↗