Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.3.14 (ATP synthase)
7,042 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies were carried out with intact mitochondria isolated from human astrocytoma, oat cell carcinoma and melanoma which were propagated in athymic mice. These human tumor mitochondria were capable of coupled oxidative phosphorylation. They also showed significant uncoupler-stimulated ATPase if defatted bovine serum albumin was included in the assay media. However, the uncoupler response curves were different and the magnitude of the ATPase activity was lower than could be obtained with mitochondria of a normal tissue, such as liver. Some of these characteristics were also exhibited by mitochondria from several animal hepatomas and Ehrlich ascites tumor. In the three tumors studied, mitochondria from oat cell carcinoma were more labile, whereas higher respiratory control ratios and greater stimulation of ATPase by uncouplers were obtained with melanoma mitochondria. The mitochondrial ATPase was not the major cellular ATPase in any of the three tumors. This was indicated by a low inhibition of the ATPase activity of tumor cell homogenates by oligomycin. A very large fraction of the cellular ATPase activities was recovered in the microsomal fractions.
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PMID:Oxidative phosphorylation and ATPase activities of human tumor mitochondria. 624 84

Certain lipophilic cations have been reported to display anticarcinoma activities because of their selective uptake and retention by mitochondria of cancer cells. Thus, these agents may comprise a unique class of agents directed against carcinoma. After screening more than 1000 lipophilic cations, we found that the monovalent lipophilic cation, 2,6-bis(4-amino-phenyl)-4-[4-(dimethylamino)phenyl]thiopyrylium chloride (AA1), displayed remarkable anticarcinoma activity both in vitro and in vivo. Unlike most other lipophilic cations, AA1 is stable and displays minimal light sensitivity. In vitro testing showed that AA1 was 10 times more toxic to the carcinoma cell line CX-1 than to the normal epithelial cell line CV-1. In vivo animal experiments showed that AA1 significantly prolonged the survival of mice implanted with tumors. For C57BL x DBA/2 F1 mice implanted with the mouse bladder carcinoma cell line, MB49, the treated:control ratio was 344%. For Swiss nu/nu mice implanted i.p. with the human melanoma cell line, LOX, the treated:control ratio was 341%. The most significant observation was obtained with Swiss nu/nu mice that were implanted i.p. with the human ovarian cell line, OVCAR-III. The treated:control ratio in this situation was greater than 450%. In all these tumor models, AA1 produced minimal toxicities. AA1 exhibited little inhibition of electron transport in isolated rat liver mitochondria; however, it inhibited mitochondrial ATPase with 50% inhibitory concentration of 6 microM. Compared with previously reported anticarcinoma lipophilic cations such as rhodamine 123 and dequalinium chloride, AA1 appeared to display more effective in vivo anticarcinoma activity. Thus, AA1 could be considered for further clinical development as a candidate for anticarcinoma chemotherapy.
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PMID:AA1, a newly synthesized monovalent lipophilic cation, expresses potent in vivo antitumor activity. 813 49

With the exception of two cases, keratin is not expressed in cultured human melanoma cells. Using 2D-PAGE, immunological and electron microscopic analyses, we found keratin subunits in five established cultured cell lines derived from primary, recurrent and metastasized melanomas. The keratin subunits were composed of K1, K5, K10, K14, K15 and K18 in all cell lines examined, together with vimentin. In addition, K8, K16 and K18 expression were demonstrated in recurrent and metastasized cell lines. The results of the present and our previous study [Katagata Y, et al. J Dermatol Sci 1996;13:219-227] indicate that expression of keratin in melanoma cells may be a universal phenomenon. A specific increase in the proportion of K5 among the keratin subunits was suggestive of the nature of melanoma cells. Moreover, we detected two polypeptides that migrated on 2D-PAGE at positions which did not correspond to those of any keratin subunit. The amino acid sequences of these two polypeptides were determined; one was the human ATP synthase alpha-chain but the other did not match any known polypeptide in our homology search.
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PMID:Keratin expression and its significance in five cultured melanoma cell lines derived from primary, recurrent and metastasized melanomas. 914 75

The synthesis of keratin is considered to occur in epithelial and epidermal cells. Previous studies have not reported on keratin synthesis within melanocytes that derive from neural crest cells. Epithelial and neural crest cells originally develop from ectodermal tissue. We previously reported that the expression of keratin is a universal phenomenon seen in cultured melanoma cell lines, as demonstrated by two-dimensional polyacrylamide gel electrophoresis, western blot, and electron microscopy analyses. To further investigate the specificity of keratin function in melanocytic cells, we first examined the presence of keratin proteins in cultured human melanocytes, and unexpectedly found keratin subunits in melanocytes by the above-mentioned procedures. The keratin (K) subunits were composed of K1, K5, K8, K10, K14, K16, and K18, together with vimentin. Neural crest cells, which contain immature embryonic melanocytes developing from ectoderm, already expressed keratins; however, under electron microscopy, the expressed keratin did not form filamentous structures. Although the ATP synthase alpha-chain, which is expressed universally in cultured epidermal tumor cell lines, was also expressed in cultured melanocytes and neural crest cells, a novel malignant melanoma-related protein (MMRP) was absent in melanocytes and neural crest cells. We concluded that keratin subunits are present in both cells, but do not construct keratin filaments.
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PMID:Keratin subunit expression in human cultured melanocytes and mouse neural crest cells without formation of filamentous structures. 1053 84

A complex prescription (CP) used traditionally for the treatment of vitiligo was prepared from water extract of eight plant materials. To study the mechanism of this preparation its effect on gene expression of B-16 murine melanoma cells was estimated using differential display method (DDRT-PCR). The results showed that the complex prescription was effective in activating the mitochondrial ATP synthase-6 (ATPase-6) gene expression in B-16 murine melanoma cells. This activity may play an important role in its treatment of vitiligo.
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PMID:A complex prescription for vitiligo activates mitochondrial ATP synthase-6 expression in B-16 murine melanoma cells. 1513

We employed human SK-MEL-28 cells as a model system to identify cellular proteins that accompany N-(4-methyl)phenyl-O-(4-methoxy)phenyl-thionocarbamate (MMTC)-induced apoptosis based on a proteomic approach. Cell viability tests revealed that SK-MEL-28 skin cancer cells underwent more cell death than normal HaCaT cells in a dose-dependent manner after treatment with MMTC. Two-dimensional electrophoresis in conjunction with matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry analysis or computer matching with a protein database further revealed that the MMTC-induced apoptosis is accompanied by increased levels of caspase-1, checkpoint suppressor-1, caspase-4, NF-kappaB inhibitor, AP-2, c-Jun-N-terminal kinase, melanoma inhibitor, granzyme K, G1/S specific cyclin D3, cystein rich protein, Ras-related protein Rab-37 or Ras-related protein Rab-13, and reduced levels of EMS (oncogene), ATP synthase, tyrosine-phosphatase, Cdc25c, 14-3-3 protein or specific structure of nuclear receptor. The migration suppressing effect of MMTC on SK-MEL-28 cell was tested. MMTC suppressed the metastasis of SK-MEL-8 cells. It was also identified that MMTC had little angiogenic effect because it did not suppress the proliferation of HUVEC cell line. These results suggest that MMTC is a novel chemotherapeutic and metastatic agents against the SK-MEL-28 human melanoma cell line.
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PMID:Proteomic analysis and the antimetastatic effect of N-(4-methyl)phenyl-O-(4-methoxy) phenyl-thionocarbamate-induced apoptosis in human melanoma SK-MEL-28 cells. 1659 96

A triazine-based combinatorial library of small molecules was screened in zebrafish to identify compounds that produced interesting phenotypes. One compound (of 1536 screened) induced a dramatic increase in the pigmentation of early stage zebrafish embryos. This compound, PPA, was also found to increase pigmentation in cultured mammalian melanocytes. The cellular target was identified as the mitochondrial F1F0-ATP synthase (ATPase) by affinity chromatography. Oligomycin, a small molecule known to inhibit the mitochondrial ATPase, competed with PPA for its cellular target in melanocytes. In addition, PPA was shown to alter the membrane potential of mitochondria, consistent with inhibition of the mitochondrial ATPase. Thus, PPA has been successfully used as a chemical probe in a forward chemical genetic approach to establish a link between the phenotype and the protein. The results attest to the power of screening small molecule libraries in zebrafish as a means of identifying mammalian targets and suggest the mitochondrial ATPase as a target for modulating pigmentation in both melanocytes and melanoma cells.
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PMID:Identification of the F1F0 mitochondrial ATPase as a target for modulating skin pigmentation by screening a tagged triazine library in zebrafish. 1688 Sep 68

Metastasis is a complex, multistep process by which a cancer cell leaves the primary tumor, travels to a distant site via the circulatory system, and establishes a secondary cancer. A deeper understanding of the molecular events underlying metastasis will provide information that will be useful for the development of new diagnostic and therapeutic strategies. The B16 and B16F10 mouse melanoma cell lines are widely used as model system for studying many aspects of cancer biology including metastasis. Compared with B16, which has a low metastatic potential, the highly metastatic cell line B16F10 displayed a higher metastatic ability along with higher expression levels of the metastasis-associated phosphatase of regenerating liver-3 (PRL-3). B16 cells transfected with PRL-3 cDNA (B16-PRL3) had metastatic abilities comparable to those of Bl16F10 cells. To study the molecular mechanisms that underlie metastasis, the proteomes of the B16, B16F10, and B16-PRL3 cell lines were compared using two-dimensional differential in-gel electrophoresis. Proteins that varied significantly in levels between these cell lines were selected and identified using mass spectrometry. Interestingly, many proteins, especially those present in membrane fractions, were similarly up- or downregulated in both the Bl16F10 and B16-PRL3 cells lines compared to B16 cell lines. The list of similarly regulated proteins included heat shock protein 70, fascin-1, septin-6, ATP synthase beta subunit, and bone morphogenic protein receptor type IB. These proteins may play a causal role in PRL-3-mediated metastasis. These investigations open an avenue for the further characterization of the molecular mechanisms that underlie metastasis.
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PMID:Comparative proteomic analysis of mouse melanoma cell line B16, a metastatic descendant B16F10, and B16 overexpressing the metastasis-associated tyrosine phosphatase PRL-3. 1980 91

Considering that stimulation of melanogenesis may lead to alterations of cellular responses, besides melanin production, our main goal was to study the cellular effects of melanogenesis stimulation of B16-F10 melanoma cells. Our results show increased levels of the reactive oxygen species after 15 h of melanogenesis stimulation. Following 48 h of melanogenesis stimulation, proliferation was inhibited (by induction of cell cycle arrest in the G1 phase) and the expression levels of p21 mRNA were increased. In addition, melanogenesis stimulation did not induce cellular senescence. Proteomic analysis demonstrated the involvement of proteins from other pathways besides those related to the cell cycle, including protein disulfide isomerase A3, heat-shock protein 70, and fructose biphosphate aldolase A (all up-regulated), and lactate dehydrogenase (down-regulated). In RT-qPCR experiments, the levels of pyruvate kinase M2 mRNA dropped, whereas the levels of ATP synthase (beta-F1) mRNA increased. These data indicate that melanogenesis stimulation of B16-F10 cells leads to alterations in metabolism and cell cycle progression that may contribute to an induction of cell quiescence, which may provide a mechanism of resistance against cellular injury promoted by melanin synthesis.
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PMID:Melanogenesis stimulation in B16-F10 melanoma cells induces cell cycle alterations, increased ROS levels and a differential expression of proteins as revealed by proteomic analysis. 2266

To address pivotal roles of cell surface F1/FO ATP synthase in the development of acidic microenvironment in tumor tissues, we investigated effects of shear stress stimulation on the cultured human breast cancer cells, MDA-MB-231 and MDA-MB-157, or human melanoma cells, SK-Mel-1. Shear stress stimulation (0.5-5.0 dyn/cm(2)), the levels of which are similar to those produced by the interstitial flow, induced strength-dependent corelease of ATP and H(+) from the cells, which triggered CO2 gas excretion. In contrast, the same level of shear stress stimulation did not induce significant ATP release and CO2 gas excretion from the control human mammary epithelial cells (HMEC). Marked immunocytochemical and mRNA expression of cell surface F1/FO ATP synthase, vacuolar-ATPase (V-ATPase), carbonic anhydrase type IX, and ectonucleoside triphosphate diphosphohydrolase (ENTPDase) 3 were detected in MDA-MB-231 cells, but little or no expression on the HMEC. Pretreatment with cell surface F1/FO ATP synthase inhibitors, but not cell surface V-ATPase inhibitors, caused a significant reduction of the shear stress stimulation-mediated ATP release and CO2 gas excretion from MDA-MB-231 cells. The ENTPDase activity in the shear stress-loaded MDA-MB-231 cell culture medium supernatant increased significantly in a time-dependent manner. In addition, MDA-MB-231 cells displayed strong staining for purinergic 2Y1 (P2Y1) receptors on their surfaces, and the receptors partially colocalized with ENTPDase 3. These findings suggest that cell surface F1/FO ATP synthase, but not V-ATPase, may play key roles in the development of interstitial flow-mediated acidic microenvironment in tumor tissues through the shear stress stimulation-induced ATP and H(+) corelease and CO2 gas production.
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PMID:Cell surface F1/FO ATP synthase contributes to interstitial flow-mediated development of the acidic microenvironment in tumor tissues. 2406 18


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