Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have found high affinity binding of insulin not only in rat liver and kidney, but also in testis and male sex accessory tissues, prostate, seminal vesicle, and epididymis. We have studied particularly the characteristics of insulin binding in the testis. Membranes sedimenting at 100,000 X g showed the highest binding after 6-20 h of incubation at 0 C. Higher temperatures (15 and 25 C) resulted in lower binding. More than 90% of membrane-bound radioactivity after long incubations at 0 C was eluted at the same position as insulin by Sephadex G-50 chromatography. Membranes could be stored at -80 C for several weeks without loss of activity. Studies on binding specificity showed the following order of competition relative to insulin (100): desalanine insulin (84), proinsulin (2), and desoctapeptide insulin (1). Other peptidic hormones, LH, FSH, PRL, GH, glucagon, and ACTH-(1-24) were totally ineffective. Scatchard representation of the binding data could be resolved into two components with respective affinity constant (Ka) of 1.6 X 10(9) M-1 and 3 X 10(6) M-1. Testicular high affinity binding in adult rats did not vary after 3 days of starvation. However, it increased with age from 1-6 months. By contrast, in rat liver, this type of binding increased after starvation but decreased slightly at 6 months of age. These results show that testicular insulin receptors are similar to those of the liver but may have a different physiological control.
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PMID:Specific insulin binding sites in rat testis: characterization and variation. 703 Jul 19

The fine structure of the intraerythrocytic asexual forms of Plasmodium falciparum is described before and during treatment with chloroquine (CQ) in the venous blood of 27 Saudi patients whe were heavily infected with the parasite. Before treatment, the "pear" shaped merozoite was rapidly transformed into a ring-shaped trophozoite. This was enclosed in a parasitophorous vacuole bounded by a single membrane derived from the host erythrocyte. The parasite feeding mechanism involves several previously undescribed endocytic organelles that function to internalize the erythrocyte haemoglobin into the central food vacuole (FV). Crystalline pigment particles, the trophozoite final metabolic product, accumulated in residual membrane-bound vacuoles. Fully mature schizonts releasing newly produced merozoites were seen for the first time at the electron microscopy level. During treatment, the parasite cytoplasm appeared divided into a vacuolated, electron-dense, ribosomal region and a less dense FV. The feeding mechanism was apparently inhibited; this was indicated by severe damage to the FV and absence of the endocytic organelles, seen in the healthy parasite, causing its starvation and death.
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PMID:Falciparum malaria in naturally infected human patients: VIII. Fine structure of intraerythrocytic asexual forms before and during chloroquine treatment. 795 97

The widespread distribution of enzymes classed as semicarbazide-sensitive amine oxidases (SSAO enzymes) throughout a very wide range of eukaryotic as well as prokaryotic organisms encourages the aspirations of those who wish to demonstrate physiological, pathological or pharmacological importance. Such enzymes are found in several tissues of mammals, both freely soluble, as in blood plasma, and membrane-bound, for example, in smooth muscle and adipose tissue. While they are capable of deaminating many amines with the production of an aldehyde and hydrogen peroxide, doubt still surrounds the identity of the most important endogenous substrates for these enzymes. At present, methylamine and aminoacetone appear to head the list of candidates. The possibility that SSAO enzymes can convert amine substrates to highly toxic metabolites is illustrated by the production of acrolein from the xenobiotic amine, allylamine and formaldehyde and methylglyoxal from methylamine and aminoacetone, respectively. Activities of SSAO enzymes may be influenced by physiological changes, such as pregnancy or pathologically by disease states, including diabetes, tumours and burns. Increased deamination of aminoacetone by tissue and plasma SSAO enzymes as a result of its increased production from L-threonine in conditions such as exhaustion, starvation and diabetes mellitus may be harmful. Such dangers could be mitigated either physiologically by a compensatory reduction in SSAO activity or pharmacologically by treatment with inhibitors of SSAO.
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PMID:Some aspects of the pathophysiology of semicarbazide-sensitive amine oxidase enzymes. 858 67

The native V1 complex of the tobacco hornworm vacuolar type ATPase (V-ATPase) was purified from cytosolic extracts of molting larval midgut. It consisted of the established V-ATPase subunits A, B, and E along with the 14-kDa subunit F and the novel 13-kDa subunit G. The final amount of purified V1 complex made up an unexpectedly high 2% of the total cytosolic protein, with a yield of approximately 0.4 mg/g of tissue. An equally high amount of cytosolic V1 complex was obtained from starving intermolt larvae. By contrast, the cytosolic V1 pool was reduced drastically in feeding intermolt larvae or in larvae that had been refed after starvation. The activity of the membrane-bound V-ATPase holoenzyme was inversely related to the size of the cytosolic V1 pool, suggesting that the insect plasma membrane V-ATPase is regulated by reversible disassembly of the V1 complex as a function of the feeding condition of the larvae. Like F1-ATPases, the purified V1 complex exhibited Ca2+-dependent ATPase activity and, in the presence of 25% methanol, exhibited Mg2+-dependent ATPase activity. Therefore, we designate the native V1 complex, V1-ATPase. Both enzyme activities were completely inhibited by micromolar N-ethylmaleimide. In contrast to the Ca2+-dependent V1-ATPase activity, the Mg2+/methanol-dependent V1-ATPase activity did not decrease with the incubation time and thus was not inhibited by ADP. Methanol appears to induce a conformational change of the V1 complex, leading to enzymatic properties of the V1-ATPase that are similar to those of the membrane-bound V-ATPase holoenzyme. This is the first time that a native and enzymatically active V1 complex has been purified from the cytosol.
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PMID:Purification and properties of a cytosolic V1-ATPase. 870 48

Upon fractionation of a post mitochondrial supernatant from rat liver, phosphorylase kinase activity was largely recovered in the cytosol and the smooth endoplasmic reticulum (SER) fraction. The presence of phosphorylase kinase in SER vesicles was not due to an interaction of the enzyme with glycogen particles, since previous elimination of SER glycogen either by 48 h animal starvation or by treatment of the membrane fraction with alpha-amylase did not significantly alter phosphorylase kinase activity content. Washing of the initial pellet of SER fraction (crude SER) by dilution and recentrifugation, released in the supernatant an amount of phosphorylase kinase activity, which is dependent on: i) the degree of dilution, ii) the number of washes, iii) the ionic strength of the washing solution and iii) the presence or absence of Ca2+. Crude SER-associated phosphorylase kinase was marginally affected by increased concentrations of antibody against rabbit skeletal muscle holoenzyme which nevertheless drastically inhibited cytosolic enzyme activity, while it showed a higher resistance to partial proteolysis and a different Western blotting profile with anti-phosphorylase kinase when compared with the soluble kinase. A small but significant fraction of SER phosphorylase kinase was strongly associated with the microsomal fraction being partly extractable only in presence of detergents. This membrane-bound enzyme form exhibited an alkaline pH optimum, in contrast to the neutral pH optima of both soluble and weakly associated phosphorylase kinase.
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PMID:The association of phosphorylase kinase with membranes of rat liver smooth endoplasmic reticulum. 871 29

Phagocytosis of collagen fibrils by fibroblasts is an important pathway for degradation of extracellular matrix in mature connective tissues. To study regulatory mechanisms in phagocytosis, 2-microns fluorescent beads coated with either collagen (COL) or bovine serum albumin (BSA) were incubated with human gingival fibroblasts in vitro. For these studies single cell suspensions were prepared by trypsinization, and bead internalization and collagen receptor expression were assessed by flow cytometry. After 3-h incubations, up to 8-fold more cells internalized COL beads than BSA-coated beads. Increased collagen coating concentration was associated with elevated proportions of cells that internalized COL beads, and was observed also in the presence of competing fibronectin-coated beads. The number of beads per cell and the percent of phagocytic cells increased proportionally with higher bead loadings. At > 4 beads per cell a maximum of approximately 80% of cells were phagocytic. Cells reacted with mAbs against the alpha 1, alpha 2, and alpha 3 integrin subunits were, respectively, 5%, 98% and 93% positively stained above background controls. All cells that internalized COL beads exhibited alpha 2 staining but there were large proportions of phagocytic cells that were not stained for alpha 1. In unfixed cells, bead internalization caused an immediate reduction of surface staining of membrane-bound alpha 2 by approximately 55% which returned to control levels within 3 h, indicating that cell-surface alpha 2 was internalized by phagocytosis. Preincubation of cells with up to 8 COL beads per cell reduced the proportion of phagocytic cells and the number of internalized beads after a second COL bead incubation 4 h later. To assess the relationship between the percent of phagocytic cells and alpha 2 integrin levels, serum starvation and cycloheximide experiments were conducted. Compared to controls, serum starvation for 24 h induced a 3.2-fold increase of cells internalizing COL beads but did not alter alpha 2 staining levels. In contrast, 3 h cycloheximide treatment reduced alpha 2 staining to 60% of control levels and this treatment also inhibited COL bead internalization. GRGDTP peptide as well as mAbs against the alpha 1 and alpha 2 subunits significantly reduced internalization of COL beads by 1.8 to 2.6-fold, whereas GRGESP peptide and alpha 3 mAb exerted no effect. Internalization of BSA beads was not affected by any of these treatments. Collectively, these data indicate that the alpha 2 integrin, along with other, as yet unidentified components, is likely involved in COL bead internalization. The alpha 2 integrin subunit is rapidly recycled or synthesized following a phagocytic load. In contrast, the alpha 1 integrin is not directly required for phagocytosis but may regulate the internalization step.
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PMID:Role of integrins in regulation of collagen phagocytosis by human fibroblasts. 881 24

In the yeast Saccharomyces cerevisiae, phosphorylation of translation initiation factor eIF2 by protein kinase GCN2 leads to increased translation of the transcriptional activator GCN4 in amino acid-starved cells. The GCN1 and GCN20 proteins are components of a protein complex required for the stimulation of GCN2 kinase activity under starvation conditions. GCN20 is a member of the ATP-binding cassette (ABC) family, most of the members of which function as membrane-bound transporters, raising the possibility that the GCN1/GCN20 complex regulates GCN2 indirectly as an amino acid transporter. At odds with this idea, indirect immunofluorescence revealed cytoplasmic localization of GCN1 and no obvious association with plasma or vacuolar membranes. In addition, a fraction of GCN1 and GCN20 cosedimented with polysomes and 80S ribosomes, and the ribosome association of GCN20 was largely dependent on GCN1. The C-terminal 84% of GCN20 containing the ABCs was found to be dispensable for complex formation with GCN1 and for the stimulation of GCN2 kinase function. Because ABCs provide the energy-coupling mechanism for ABC transporters, these results also contradict the idea that GCN20 regulates GCN2 as an amino acid transporter. The N-terminal 15 to 25% of GCN20, which is critically required for its regulatory function, was found to interact with an internal segment of GCN1 similar in sequence to translation elongation factor 3 (EF3). Based on these findings, we propose that GCN1 performs an EF3-related function in facilitating the activation of GCN2 by uncharged tRNA on translating ribosomes. The physical interaction between GCN20 and the EF3-like domain in GCN1 could allow for modulation of GCN1 activity, and the ABC domains in GCN20 may be involved in this regulatory function. A human homolog of GCN1 has been identified, and the portion of this protein most highly conserved with yeast GCN1 has sequence similarity to EF3. Thus, similar mechanisms for the detection of uncharged tRNA on translating ribosomes may operate in yeast and human cells.
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PMID:Evidence that GCN1 and GCN20, translational regulators of GCN4, function on elongating ribosomes in activation of eIF2alpha kinase GCN2. 923 5

Stress conditions lead to a variety of physiological responses at the cellular level. Autophagy is an essential process used by animal, plant, and fungal cells that allows for both recycling of macromolecular constituents under conditions of nutrient limitation and remodeling the intracellular structure for cell differentiation. To elucidate the molecular basis of autophagic protein transport to the vacuole/lysosome, we have undertaken a morphological and biochemical analysis of this pathway in yeast. Using the vacuolar hydrolase aminopeptidase I (API) as a marker, we provide evidence that the autophagic pathway overlaps with the biosynthetic pathway, cytoplasm to vacuole targeting (Cvt), used for API import. Before targeting, the precursor form of API is localized mostly in restricted regions of the cytosol as a complex with spherical particles (termed Cvt complex). During vegetative growth, the Cvt complex is selectively wrapped by a membrane sac forming a double membrane-bound structure of approximately 150 nm diam, which then fuses with the vacuolar membrane. This process is topologically the same as macroautophagy induced under starvation conditions in yeast (Baba, M., K. Takeshige, N. Baba, and Y. Ohsumi. 1994. J. Cell Biol. 124:903-913). However, in contrast with autophagy, API import proceeds constitutively in growing conditions. This is the first demonstration of the use of an autophagy-like mechanism for biosynthetic delivery of a vacuolar hydrolase. Another important finding is that when cells are subjected to starvation conditions, the Cvt complex is now taken up by an autophagosome that is much larger and contains other cytosolic components; depending on environmental conditions, the cell uses an alternate pathway to sequester the Cvt complex and selectively deliver API to the vacuole. Together these results indicate that two related but distinct autophagy-like processes are involved in both biogenesis of vacuolar resident proteins and sequestration of substrates to be degraded.
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PMID:Two distinct pathways for targeting proteins from the cytoplasm to the vacuole/lysosome. 941 64

Glypicans are a group of membrane-bound heparan sulfate proteoglycans (HSPG) that are tissue specific and developmentally regulated. Transcripts for avian glypican are found in endocardial cushions, limb buds, somites and forebrain of early chick embryos. Since avian glypican is not well characterized, the cellular localization, regulation of expression, and possible function during cardiac development have been studied. A polyclonal antibody was raised against a 20-amino acid peptide corresponding to an antigenic sequence within avian glypican core protein. The antibody recognized the expressed core protein in bacterial lysates and the endogenous HSPG in the proteoglycan fraction from chick forebrain. Immunolocalization studies indicated that the core protein is associated with cell membranes. The level of mRNA for avian glypican in MEQC (myc embryonic quail cardiomyocytes) grown in medium containing 10% fetal calf serum was compared to the message levels in cells grown without serum for 3 days. By Northern analysis, glypican transcripts were increased markedly after serum starvation. Up-regulation of glypican transcripts by serum withdrawal was partially prevented by addition of TGFbeta-1 and bFGF, suggesting that these growth factors may regulate its expression. MEQC cells deprived of serum migrated into clumps that could be blocked by an antisense OND (oligodeoxynucleotide) to the mRNA encoding the avian glypican. The same antisense OND inhibited the migration of endothelial cells from chick tubular heart explants over the surface of collagen gels. These results indicate that avian glypican may play a role in cell migration during development of endocardial cushions.
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PMID:Structure, regulation and function of avian glypican. 951 30

We studied the interaction between the multidrug transporter, P-glycoprotein, and two compounds that interact with it: vinblastine, a classical substrate of the pump, and verapamil, a classical reverser. Steady-state levels of accumulation of these two drugs were determined in a multidrug resistant P388 leukemia cell line, P388/ADR. The time course of accumulation of these drugs, and the effect of energy starvation and the presence of chloroquine on the level of their steady-state accumulation were quite disparate. Vinblastine inhibited the accumulation of verapamil whereas it enhanced the accumulation of daunomycin, another classic substrate of P-glycoprotein. Verapamil did not compete with the intracellular binding sites of vinblastine. In all these aspects, vinblastine behaved as a typical substrate of P-glycoprotein but verapamil did not. Our data suggest that verapamil is a reverser of P-glycoprotein but that its intracellular accumulation is not affected by this membrane-bound transporter.
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PMID:Drug accumulation in the presence of the multidrug resistance pump: dissociation between verapamil accumulation and the action of P-glycoprotein. 960 21


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