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)

Infection of keratinocytes with high risk human Papilloma virus causes immortalization, and when followed by further mutations, leads to cervical cancer and other anogenital tumors. Here we monitor the progressive loss of robustness in an in vitro model of the early stages of transformation that comprises normal keratinocytes and progressive passages of HPV16 immortalized cells. As transformation progresses, the cells acquire higher proliferation rates and gain the ability to grow in soft agar. Concurrently, the cells lose robustness, becoming more sensitive to serum starvation and DNA damage by Cisplatin. Loss of robustness in the course of transformation correlates with significant reductions in the activities of the anti-apoptotic proteins PKB/Akt, Erk, Jnk and p38 both under normal growth conditions and upon stress. In parallel, loss of robustness is manifested by the shrinkage of the number of growth factors that can rescue starving cells from apoptosis, with the emergence of dependence solely on IGF1. Treatment with IGF1 activates PKB/Akt and Jnk and through them inhibits p53, rescuing the cells from starvation. We conclude that transformation in this model induces higher susceptibility of cells to stress due to reduced anti-apoptotic signaling and hyper-activation of p53 upon stress.
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PMID:Loss of robustness and addiction to IGF1 during early keratinocyte transformation by human Papilloma virus 16. 1762 50

Infection with the malaria parasite Plasmodium falciparum leads to widely different clinical conditions in children, ranging from mild flu-like symptoms to coma and death. Despite the immense medical implications, the genetic and molecular basis of this diversity remains largely unknown. Studies of in vitro gene expression have found few transcriptional differences between different parasite strains. Here we present a large study of in vivo expression profiles of parasites derived directly from blood samples from infected patients. The in vivo expression profiles define three distinct transcriptional states. The biological basis of these states can be interpreted by comparison with an extensive compendium of expression data in the yeast Saccharomyces cerevisiae. The three states in vivo closely resemble, first, active growth based on glycolytic metabolism, second, a starvation response accompanied by metabolism of alternative carbon sources, and third, an environmental stress response. The glycolytic state is highly similar to the known profile of the ring stage in vitro, but the other states have not been observed in vitro. The results reveal a previously unknown physiological diversity in the in vivo biology of the malaria parasite, in particular evidence for a functional mitochondrion in the asexual-stage parasite, and indicate in vivo and in vitro studies to determine how this variation may affect disease manifestations and treatment.
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PMID:Distinct physiological states of Plasmodium falciparum in malaria-infected patients. 1807 67

The infection-related expression of a Heterobasidion annosum (Fr.) Bref. sensu lato (s.l.) putative cytochrome P450 gene (CPM2) was analysed with realtime quantitative PCR. CPM2 was highly expressed after 20 days of growth in bark of living spruce trees, and up-regulated by nitrogen starvation on artificial media. Infection of pine seedlings in the presence of high-carbon medium results in low expression levels of CPM2, thus indicating that starvation is the primary regulatory factor for induction of this gene. The predicted cpm2 protein contains 507 amino acids with an estimated molecular mass of 56.1 kDa, and display all conserved amino acids of the cytochrome P450 protein family. The protein has a high similarity to the ord1/ordA O-methylsterigmatocystin oxidoreductases from Aspergillus flavus/A. parasiticus, responsible for catalysing the final step in aflatoxin biosynthesis. Results indicate that cpm2 is potentially important for pathogenicity in H. annosum s.l.
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PMID:A fungal cytochrome P450 is expressed during the interaction between the fungal pathogen Heterobasidion annosum sensu lato and conifer trees. 1829 2

An experimental model of haemosiderosis, using the chicken, was developed to examine the distribution of iron in the liver following an injection of iron dextran and to allow calibration of image analysis readings. Image analysis was used as a tool to quantify the stainable iron present in hepatic tissue obtained from wild and captive birds presented for necropsy. A retrospective study of 180 necropsy cases, representing 40 different species of bird, is described. Statistical evaluation of the amount and distribution of stainable iron in the liver tissue of birds from different taxonomic orders indicated that the concentration of iron measured in liver tissue was significantly different in different species of bird. The results of the study showed that hepatic haemosiderosis is a common histological finding in most avian species examined. Although not necessarily associated with overt liver disease, it is often associated with concurrent malignant and infectious diseases. The presence of excess stainable iron in the liver is probably a reflection of an altered iron metabolism associated with increased turnover of tissue iron. This alteration may occur following starvation or trauma.
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PMID:A quantitative assessment of haemosiderosis in wild and captive birds using image analysis. 1864 83

Evidence increasingly suggests that ethnic differences in cardiovascular risk are partly mediated by adipose tissue biology, which refers to the regional distribution of adipose tissue and its differential metabolic activity. This paper proposes a novel evolutionary hypothesis for ethnic genetic variability in adipose tissue biology. Whereas medical interest focuses on the harmful effect of excess fat, the value of adipose tissue is greatest during chronic energy insufficiency. Following Neel's influential paper on the thrifty genotype, proposed to have been favoured by exposure to cycles of feast and famine, much effort has been devoted to searching for genetic markers of 'thrifty metabolism'. However, whether famine-induced starvation was the primary selective pressure on adipose tissue biology has been questioned, while the notion that fat primarily represents a buffer against starvation appears inconsistent with historical records of mortality during famines. This paper reviews evidence for the role played by adipose tissue in immune function and proposes that adipose tissue biology responds to selective pressures acting through infectious disease. Different diseases activate the immune system in different ways and induce different metabolic costs. It is hypothesized that exposure to different infectious disease burdens has favoured ethnic genetic variability in the anatomical location of, and metabolic profile of, adipose tissue depots.
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PMID:Ethnic variability in adiposity and cardiovascular risk: the variable disease selection hypothesis. 1882 Mar 20

Mycobacterium fortuitum is a non-tubercular fast growing pathogenic mycobacteria whose virulence factors have not been studied. Infection of M. fortuitum ATCC 6841 in a murine infection model leads to spinning of the head in 8-12 days after infection, 20-25% mortality and a constant bacillary load in the kidney of mice, suggesting persistence. From a TnphoA insertion library, a mutant MT13 was isolated which was attenuated in virulence with lesser bacterial burden, milder and delayed spinning of the head and no mortality of mice. The significant feature of the mutant was its failure to persist in kidney and thus the persistent bacillary load characteristic exhibited by the wild type strain was not observed. The insertion of transposon in MT13 was mapped in a region of the genome, which showed homology to Rv3291c of M. tuberculosis, annotated as a transcriptional regulatory factor and reported to be up regulated in nutrient starvation and anaerobic persistent states. Complementation of MT13 with rv3291c resulted in restoration of wild type characteristics including persistence in kidney suggesting the role of a Rv3291c homolog in the virulence and persistence of M. fortuitum.
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PMID:A transposon insertion mutant of Mycobacterium fortuitum attenuated in virulence and persistence in a murine infection model that is complemented by Rv3291c of Mycobacterium tuberculosis. 1893 Jan 29

Autophagy is a cellular pathway involved in protein and organelle degradation, which is likely to represent an innate adaptation to starvation. In times of nutrient deficiency, the cell can self-digest and recycle some nonessential components through nonselective autophagy, thus sustaining minimal growth requirements until a food source becomes available. Over recent years, autophagy has been implicated in an increasing number of clinical scenarios, notably infectious diseases, cancer, neurodegenerative diseases, and autoimmunity. The recent identification of the importance of autophagy genes in the genetic susceptibility to Crohn's disease suggests that a selective autophagic response may play a crucial role in the pathogenesis of common complex immune-mediated diseases. In this review, we discuss the autophagic mechanisms, their molecular regulation, and summarize their clinical relevance. This progress has led to great interest in the therapeutic potential of manipulation of both selective and nonselective autophagy in established disease.
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PMID:Autophagy: from basic science to clinical application. 1942 Nov 82

Invasive fungal infections of immunocompromised patients cause major problems in modern medicine and only a limited number of effective antifungals are available, making the identification of new drug targets a priority. The inhibition of primary metabolism represents a promising therapeutic strategy, but a better understanding of the metabolic processes during pathogenesis is required. Infection, invasion and maintenance within a host are very dynamic events and fungal metabolism has to adapt to these changes. Glycolysis, gluconeogenesis and starvation all contribute to successful host colonisation, but the temporal and spatial resolution of their specific importance is poorly understood. Knowledge about the metabolic requirements of pathogenic fungi during infection could lead to the identification of new classes of antifungals, which allow the treatment of otherwise life-threatening infections.
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PMID:Fungal metabolism in host niches. 1953 85

The interferon (IFN)-gamma-inducible tryptophan degrading enzyme indoleamine 2,3-dioxygenase (IDO) has not only been recognized as a potent antimicrobial effector molecule for the last 25 years but was recently found also to have potent immunoregulatory properties. In this study, we provide evidence that both tryptophan starvation and production of toxic tryptophan metabolites are involved in the immunoregulation mediated by IDO, whereas tryptophan starvation seems to be the only antibacterial effector mechanism. A long-studied controversy in the IDO research field is the seemingly contradictory effect of IDO in the defence against infectious diseases. On the one hand, IFN-gamma-induced IDO activity mediates an antimicrobial effect, while at the same time IDO inhibits T-cell proliferation and IFN-gamma production. Here, we suggest that both effects, dependent on the threshold for tryptophan, cooperate in a reasonable coherence. We found that the minimum concentration of tryptophan required for bacterial growth is 10-40-fold higher than the minimum concentration necessary for T-cell activation. Therefore, we suggest that during the first phase of infection the IDO-mediated tryptophan depletion has a predominantly antimicrobial effect whereas in the next stage, and with ongoing tryptophan degradation, the minimum threshold concentration of tryptophan for T-cell activation is undercut, resulting in an inhibition of T-cell growth and subsequent IDO activation.
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PMID:The missing link between indoleamine 2,3-dioxygenase mediated antibacterial and immunoregulatory effects. 1960 41

Autophagy is a process of self-degradation of cellular components in which double-membrane autophagosomes sequester organelles or portions of cytosol and fuse with lysosomes or vacuoles for breakdown by resident hydrolases. Autophagy is upregulated in response to extra- or intracellular stress and signals such as starvation, growth factor deprivation, ER stress, and pathogen infection. Defective autophagy plays a significant role in human pathologies, including cancer, neurodegeneration, and infectious diseases. We present our current knowledge on the key genes composing the autophagy machinery in eukaryotes from yeast to mammalian cells and the signaling pathways that sense the status of different types of stress and induce autophagy for cell survival and homeostasis. We also review the recent advances on the molecular mechanisms that regulate the autophagy machinery at various levels, from transcriptional activation to post-translational protein modification.
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PMID:Regulation mechanisms and signaling pathways of autophagy. 1965 58


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