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901.
902.
Pani A Batetta B Putzolu M Sanna F Spano O Piras S Mulas MF Bonatesta RR Amat di S Filippo C Vargiu L Marceddu T Sanna L La Colla P Dessì S 《Cellular and molecular life sciences : CMLS》2000,57(7):1094-1102
The product of the MDR1 gene (P-gp) has been implicated in the transport of cholesterol from plasma membrane to endoplasmic reticulum for esterification.
In previous studies on leukemia cell lines, we suggested that cholesterol esterification may regulate the rate of cell growth
and that the MDR1 gene might be involved in this process by modulating intracellular cholesterol esters levels. To further investigate this
matter, the rate of cell growth, cholesterol metabolism, expression of the MDR1 gene, and P-gp activity were compared in KB cell lines displaying differences in expression and function of P-gp (drug-sensitive
phenotype versus MDR phenotype). The rate of cell growth correlated with cholesterol esterification in all KB cell lines,
whereas the over-expression of MDR1 observed in the MDR cell lines was not always associated with an increased capacity of cells to esterify cholesterol. Two
known inhibitors of P-gp activity, progesterone and verapamil, strongly inhibited both cholesterol esterification and cell
proliferation in all KB cell lines, but they affected intracellular accumulation of labeled vinblastine only in MDR cell lines.
These results further support a role for cholesterol esters in the regulation of cell growth and suggest that the P-gp expressed
in MDR KB cells is not involved in the general process leading to cholesterol esterification.
Received 14 February 2000; received after revision 10 April 2000; accepted 8 May 2000 相似文献
903.
The type III inositol 1,4,5-trisphosphate receptor (InsP3R) is an important intracellular calcium (Ca2+) release channel in the pancreatic beta cell. Pancreatic beta cells secrete insulin following a characteristic change in membrane potential that leads to an increase in cytoplasmic Ca2+. Both extracellular Ca2+ and Ca2+ mobilized from InsP3-sensitive stores contribute to this increase. RIN-m5F cells, an insulin-secreting beta cell line, preferentially express the type III InsP3R. These cells have been useful in determining the regulatory properties of the type III InsP3R and the role of this isoform in an intact cell. The type III InsP3R is ideal for signal initiation because high cytoplasmic Ca2+ does not inhibit its activity. Altered insulin secretion, the result of changes in Ca2+ handling by the beta cell, has significant clinical consequences. 相似文献
904.
New insights into copper monooxygenases and peptide amidation: structure, mechanism and function 总被引:9,自引:0,他引:9
Prigge ST Mains RE Eipper BA Amzel LM 《Cellular and molecular life sciences : CMLS》2000,57(8-9):1236-1259
Many bioactive peptides must be amidated at their carboxy terminus to exhibit full activity. Surprisingly, the amides are not generated by a transamidation reaction. Instead, the hormones are synthesized from glycine-extended intermediates that are transformed into active amidated hormones by oxidative cleavage of the glycine N-C alpha bond. In higher organisms, this reaction is catalyzed by a single bifunctional enzyme, peptidylglycine alpha-amidating monooxygenase (PAM). The PAM gene encodes one polypeptide with two enzymes that catalyze the two sequential reactions required for amidation. Peptidylglycine alpha-hydroxylating monooxygenase (PHM; EC 1.14.17.3) catalyzes the stereospecific hydroxylation of the glycine alpha-carbon of all the peptidylglycine substrates. The second enzyme, peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL; EC 4.3.2.5), generates alpha-amidated peptide product and glyoxylate. PHM contains two redox-active copper atoms that, after reduction by ascorbate, catalyze the reduction of molecular oxygen for the hydroxylation of glycine-extended substrates. The structure of the catalytic core of rat PHM at atomic resolution provides a framework for understanding the broad substrate specificity of PHM, identifying residues critical for PHM activity, and proposing mechanisms for the chemical and electron-transfer steps in catalysis. Since PHM is homologous in sequence and mechanism to dopamine beta-monooxygenase (DBM; EC 1.14.17.1), the enzyme that converts dopamine to norepinephrine during catecholamine biosynthesis, these structural and mechanistic insights are extended to DBM. 相似文献
905.
Calvete JJ Costa FH Saker-Sampaio S Murciano MP Nagano CS Cavada BS Grangeiro TB Ramos MV Bloch C Silveira SB Freitas BT Sampaio AH 《Cellular and molecular life sciences : CMLS》2000,57(2):343-350
The primary structure of a lectin isolated from the red alga Bryothamnion triquetrum was established by combination of Edman degradation of sets of overlapping peptides and mass spectrometry. It contains 91 amino acids and two disulphide bonds. The primary structure of the B. triquetrum lectin does not show amino acid sequence similarity with known plant and animal lectin structures. Hence, this protein may be the paradigm of a novel lectin family. 相似文献
906.
Differential basal synthesis of Hsp70/Hsc70 contributes to interindividual variation in Hsp70/Hsc70 inducibility 总被引:7,自引:0,他引:7
Boshoff T Lombard F Eiselen R Bornman JJ Bachelet M Polla BS Bornman L 《Cellular and molecular life sciences : CMLS》2000,57(8-9):1317-1325
The source of intraspecies variation in the expression of heat shock proteins (HSPs) remains unresolved but could shed light
on differential stress tolerance and disease susceptibility. This study investigated the influence of variable basal HSP synthesis
on differential inducibility of HSP synthesis. Basal and heat-induced synthesis of the major HSP families in peripheral blood
monocytes from healthy donors (n=42) were analysed using biometabolic labelling and densitometry. Basal Hsp70/Hsc70 synthesis
and percentage induction of Hsp70/Hsc70 synthesis were significantly correlated (r=−0.57, p<0.0001), and described most accurately
by an exponential decay equation (R=0.68, R2=0.46). This regression equation suggests that increasing levels of basal Hsp70/Hsc70 synthesis are accompanied byan exponential
decrease in the percentage induction of Hsp70/Hsc70 synthesis. The model fits data from European and non-European population
groups independently, although both coefficients in the regression equation were larger for non-Europeans. This implies population
group as an additional factor influencing differential HSP expression. The differential inducibility of Hsp70/Hsc70 due to
variable basal synthesis of Hsp70/Hsc70 and based upon population group may contribute to differential stress tolerance or
disease susceptibility.
Received 27 March 2000; received after revision 19 June 2000; accepted 20 June 2000 相似文献
907.
Rieger syndrome: a clinical, molecular, and biochemical analysis 总被引:6,自引:0,他引:6
908.
Sonic hedgehog signaling pathway in vertebrate epithelial appendage morphogenesis: perspectives in development and evolution 总被引:6,自引:0,他引:6
Chuong CM Patel N Lin J Jung HS Widelitz RB 《Cellular and molecular life sciences : CMLS》2000,57(12):1672-1681
Vertebrate epithelial appendages are elaborate topological transformations of flat epithelia into complex organs that either protrude out of external (integument) and internal (oral cavity, gut) epithelia, or invaginate into the surrounding mesenchyme. Although they have specific structures and diverse functions, most epithelial appendages share similar developmental stages, including induction, morphogenesis, differentiation and cycling. The roles of the SHH pathway are analyzed in exemplary organs including feather, hair, tooth, tongue papilla, lung and foregut. SHH is not essential for induction and differentiation, but is involved heavily in morphogenetic processes including cell proliferation (size regulation), branching morphogenesis, mesenchymal condensation, fate determination (segmentation), polarizing activities and so on. Through differential activation of these processes by SHH in a spatiotemporal-specific fashion, organs of different shape and size are laid down. During evolution, new links of developmental pathways may occur and novel forms of epithelial appendages may emerge, upon which evolutionary selections can act. Sites of major variations have progressed from the body plan to the limb plan to the epithelial appendage plan. With its powerful morphogenetic activities, the SHH pathway would likely continue to play a major role in the evolution of novel epithelial appendages. 相似文献
909.