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 previously reported a series of biological events in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-intoxicated rats which resulted in elevated brain serotonin (5-HT) levels, offering a possible explanation of the acute toxicity (reduced feed intake and death) in these animals. It was thus hypothesized that depletion of central 5-HT stores should alter the TCDD-induced starvation syndrome. Brain 5-HT was selectively depleted by intracerebroventricular infusions of the neurotoxin 5,7-dihydroxytrytamine (5,7-DHT). Subsequently the animals were given a lethal dose of TCDD. In rats treated with 5,7-DHT hypothalamic 5-HT was depleted up to 90% compared to control animals, yet TCDD induced the expected reduction of bodyweight and feed intake. These results suggest that although TCDD increases central 5-HT levels as a result of increased plasma tryptophan, this may not be the main cause for reduced feed intake and lethality in these animals.
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PMID:Depletion of brain serotonin does not alter 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced starvation syndrome in the rat. 175 37

The 5 alpha-reductase, the enzyme which converts testosterone into its major "active" metabolite (dihydrotestosterone, DHT), has been found to be present in high concentration in brain structures particularly rich of myelin (white matter structures), as well as in myelin membranes. Previous ontogenetic observations seem to indicate that, during the process of myelinogenesis, the enzyme might be synthesized in the oligodendrocytes, and subsequently incorporated into the myelin membranes. It is well established that postnatal malnutrition produces a decreased formation of myelin, when starvation is performed from birth until to the 2nd or 3rd week of life; on the contrary food deprivation does not produce any significant effect on myelin accumulation when performed after the 14th day of life. The present experiments have been performed in the rat in order to study the effects of postnatal undernutrition (from birth to the 19th day of life: long malnutrition; and from the 14th to the 19th day of life: short malnutrition) on the 5 alpha-reductase activity present in the following brain structures: cerebral cortex, hypothalamus, corpus callosum, pyramidal tract, as well as in isolated myelin membranes. Undernourished animals have been killed at 20 days of age. Normally nourished animals served as controls. Long undernutrition induced a statistically significant decrease of the formation of DHT in the corpus callosum and in the pyramidal tract vs controls. On the contrary, the nutritional deficiency did not decrease the 5 alpha-reductase activity in the cerebral cortex and in the hypothalamus.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of postnatal starvation on the 5 alpha-reductase activity of the brain and of the isolated myelin membranes. 263 Mar 7

The conversion of testosterone to estradiol by aromatase and to dihydrotestosterone by 5 alpha-reductase was measured in the medial basal hypothalamus of starved and control male rats. Activities of both enzymes were significantly reduced in starved animals. Aromatase activity was 18.2 +/- 2.3 versus 29.8 +/- 5.7 fmol E2/mg protein/90 min (mean +/- SEM, P less than 0.02) and 5 alpha-reductase was 4.95 +/- 0.35 versus 5.96 +/- 0.30 pmol DHT/mg protein/90 min (P less than 0.02) for starved and control animals respectively. The results indicate that hypothalamic metabolism of testosterone is decreased during starvation. Therefore the increased sensitivity of the T-LH feedback described earlier in starved rats [4] cannot be explained by changes in central testosterone metabolism.
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PMID:Testosterone metabolism in the medial basal hypothalamus of the starved male rat. 358 55

Ovariectomized Long-Evans rats received bilateral rostral hypothalamic infusions of 5,7-dihydroxytryptamine (5,7-DHT). Neurochemical determination of catecholamines (CA) and indoleamines in the hippocampus, hypothalamus and mesencephalon revealed that 5,7-DHT infusions had no effect on CA content in these areas nor in mesencephalic serotonin or 5-hydroxyindoleacetic acid (5-HIAA). However, the neurotoxin produced significant decreases in hippocampal serotonin and 5-HIAA. Serotonin-depleted animals exhibited an increase in both spontaneous and estradiol-induced wheel running. In addition it was found that serotonin-depleted animals exhibit an enhanced activity response to starvation. Because estrogen is thought to decrease serotonergic transmission, the enhanced activity response to estrogen may be secondary to an estrogen-related exaggeration of the 5,7-DHT-induced serotonin depletion. The increased activity effect of starvation may indicate that serotonin-depleted animals do not effectively mobilize energy stored as lipid.
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PMID:Rostral hypothalamic microinfusions of 5,7 dihydroxytryptamine produce anatomically and neurochemically selective depletions of hippocampal serotonin and increase the influence of estrogen and food deprivation on locomotor activity. 405 95

Multiple myeloma (MM) is an incurable plasma cell malignancy with poor survival. Autophagy, a stress-responsive catabolic process mediated by lysosomal activity, plays a crucial role in the pathophysiology of MM. Growing evidence has indicated that dysregulated microRNAs (miRNAs) are associated with the aberrant autophagy in various human cancers. However, to date, few miRNAs have been reported to directly modulate autophagy in the pathobiology of MM. In this study, we investigated the role of MIR145-3p (microRNA 145-3p) in MM, with focus on cellular processes autophagy and cell death. Our results provided evidence that downregulation of MIR145-3p expression was associated with disease progression in human MM. MIR145-3p triggered autophagic flux through direct targeting of HDAC4 (histone deacetylase 4) in MM cells, leading to enhanced apoptosis. Silencing HDAC4 recapitulated the effects of MIR145-3p, whereas enforced expression of HDAC4 abrogated the effects of MIR145-3p. Furthermore, we showed that suppression of HDAC4 by MIR145-3p resulted in upregulation of the pro-apoptotic protein BCL2L11 and caused MTORC1 inactivation, which in turn led to enhanced autophagy and cell death. Importantly, we demonstrated that MIR145-3p mimic could potentiate the anti-MM activity of bortezomib in both in vitro and in vivo experiments. Overall, our findings indicate that MIR145-3p exerted a tumor suppression function in MM by inducing autophagic cell death and suggest that MIR145-3p-based targeted therapy would represent a novel strategy for MM treatment.Abbreviations: 3-MA: 3-methyladenine; 3'-UTR: 3'-untranslated region; 7-AAD: 7-aminoactinomycin D; ACTB: actin beta; ANXA5: annexin A5; ATG5: autophagy related 5; ATG7: autophagy related 7; B2M: beta-2-microglobulin; BAF: bafilomycin A1; BCL2L11: BCL2 like 11; Bort: bortezomib; CASP3: caspase 3; CCK-8: Cell Counting Kit-8; CQ: chloroquine; Ct: threshold cycle; ctrl: control; DAPI: 4',6-diamidino-2-phenylindole; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFP: green fluorescent protein; HDAC4: histone deacetylase 4; ISS: International Staging System; MAP1LC3B: microtubule associated protein 1 light chain 3 beta; miRNAs: microRNAs; MIR145-3p: microRNA 145-3p; MM: multiple myeloma; mRNA: messenger RNA; MTOR: mechanistic target of rapamycin kinase; MTORC1: mechanistic target of rapamycin kinase complex 1; PCs: plasma cells; PFS: progression-free survival; qRT-PCR: quantitative reverse transcription PCR; RPS6KB1: ribosomal protein S6 kinase B1; SD: standard deviation; siRNA: small interfering RNA; SQSTM1: sequestosome 1; STV: starvation; TUBB: tubulin beta class I.
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PMID:MIR145-3p promotes autophagy and enhances bortezomib sensitivity in multiple myeloma by targeting HDAC4. 3124 29