Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.62 (caspase-9)
 7,507 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Under physiological conditions, astrocytes take up L-glutamate from the synaptic gap, metabolize it to L-glutamine and return it to neurons, where L-glutamine is metabolized to L-glutamate and stored in neurotransmitter vesicles. However, under pathological conditions, such as hepatic failure, L-glutamine and ammonium are elevated globally in the brain. The Trojan horse hypothesis of L-glutamine toxicity assumes that intramitochondrial hydrolysis of L-glutamine enhances ammonium locally and leads to mitochondrial dysfunction. In the present study, we show that exposure of murine primary microglia as well as of the microglial cell-line BV-2 to L-glutamine promotes chromatin condensation and formation of crescent-like structures in the nucleus. Furthermore, L-glutamine induced an increase in annexin-V labelling, cell shrinkage (apoptotic volume decrease), cell fragmentation and formation of apoptotic bodies. Inhibition of the phosphate-activated glutaminase with 6-diazo-5-oxo-L-norleucine suppressed chromatin condensation and annexin-V labelling in L-glutamine-exposed cells. In addition, inhibition of the glutamine synthetase with L-methionine sulfoximine suppressed chromatin condensation and annexin-V labelling in ammonium-exposed cells. L-glutamine and ammonium enhanced production of reactive oxygen species, as detected with CM-H(2)DCFDA. Apoptosis, induced by L-glutamine, was inhibited either by the radical scavenger alpha-tocopherol or by the nitric oxide synthase blocker N (G)-methyl-L-arginine. Cyclosporin A, a ligand of the permeability transition pore complex component cyclophilin D, prevented L-glutamine-triggered apoptosis. Furthermore, blockade of caspase-9 activity with Z-LEHD-FMK prevented L-glutamine-triggered apoptosis. Taken together, our results indicate that hydrolysis of l-glutamine and, accordingly, accumulation of ammonium in mitochondria induce the intrinsic pathway of apoptosis, characterized by mitochondrial dysfunction and activation of caspase-9, which activates caspase-3.
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PMID:L-Glutamine-induced apoptosis in microglia is mediated by mitochondrial dysfunction. 1961 80

Pomacea canaliculata, known as an invasive freshwater snail, is also called a golden apple snail; its survival and expansion are greatly affected by temperature. In this study, high-throughput sequencing (RNA-seq) was used to perform comparative transcriptome analysis on the muscular tissue (G_M) of snails in Guangdong and Hunan. Differential gene screening was performed with FDR <0.05 and |log2FoldChange| >1 as the threshold, and a total of 1,368 differential genes were obtained (671 genes showed upregulation in snails from Guangdong, and 697 genes displayed upregulation in snails from Hunan). Fifteen genes were identified as candidate genes for the cold hardiness of Pomacea canaliculata. Among them, three genes were involved in energy metabolism (glycogen synthase, 1; DGK, 1; G6PD, 1); seven genes were involved in homeostasis regulation (HSP70, 2; BIP, 1; GPX, 1; GSTO 1, G6PD, 1; caspase-9, 1); two genes were involved in amino acid metabolism (glutamine synthetase, 1; PDK, 1); and four genes were involved in membrane metabolism (inositol-3-phosphate synthase, 1; Na+/K+-ATPase, 1; calcium-binding protein, 2). This study presents the molecular mechanisms for the cold hardiness of Pomacea canaliculata, which could provide a scientific basis for the forecast and prevention of harm from Pomacea canaliculata.
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PMID:A Comparative Transcriptomics Approach to Analyzing the Differences in Cold Resistance in Pomacea canaliculata between Guangdong and Hunan. 3283 73