Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.11.2 (prolyl hydroxylase)
 1,814 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Exposure to environmental pollutants such as polychlorinated biphenyls (PCBs) is now taken into account to partly explain the worldwide decline of amphibians. PCBs induce deleterious effects on developing amphibians including deformities and delays in metamorphosis. However, the molecular mechanisms by which they express their toxicity during the development of tadpoles are still largely unknown. A proteomics analysis was performed on developing Xenopus laevis tadpoles exposed from 2 to 5 days postfertilization to either 0.1 or 1 ppm Aroclor 1254, a PCB mixture. Two-dimensional DIGE with a minimal labeling method coupled to nanoflow liquid chromatography-tandem mass spectrometry was used to detect and identify proteins differentially expressed under PCBs conditions. Results showed that 59 spots from the 0.1 ppm Aroclor 1254 condition and 57 spots from the 1 ppm Aroclor 1254 condition displayed a significant increase or decrease of abundance compared with the control. In total, 28 proteins were identified. The results suggest that PCBs induce mechanisms against oxidative stress (peroxiredoxins 1 and 2), adaptative changes in the energetic metabolism (enolase 1, glycerol-3-phosphate dehydrogenase, and creatine kinase muscle and brain types), and the implication of the unfolded protein response system (glucose-regulated protein, 58 kDa). They also affect, at least at the highest concentration tested, the synthesis of proteins involved in normal cytogenesis (alpha-tropomyosin, myosin heavy chain, and alpha-actin). For the first time, proteins such as aldehyde dehydrogenase 7A1, CArG binding factor-A, prolyl 4-hydroxylase beta, and nuclear matrix protein 200 were also shown to be up-regulated by PCBs in developing amphibians. These data argue that protein expression reorganization should be taken into account while estimating the toxicological hazard of wild amphibian populations exposed to PCBs.
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PMID:Protein expression profiling in the African clawed frog Xenopus laevis tadpoles exposed to the polychlorinated biphenyl mixture aroclor 1254. 1901 Dec 58

Ischemia/reperfusion (I/R) unleashes cellular events that threaten organ survival. I/R affects endoplasmic reticulum (ER) integrity and initiates the unfolded protein response (UPR). The adaptive arm of the UPR attenuates ER stress by increasing expression of chaperones promoting proper protein folding. However, failure to resolve ER stress leads to apoptotis. We recently showed that prolyl hydroxylase inhibition (PHI) attenuated post-ischemic cardiac injury. We hypothesized that PHI attenuated myocardial I/R injury through modulation of the UPR. We show for the first time that PHI activates all three regulatory arms of the UPR in murine microvascular endothelial cells and in mouse hearts. Cardiac I/R activated expression of pro-apoptotic CHOP (2.8 fold, n=3, p<0.01). PHI significantly decreased CHOP expression (50%, n=3, p<0.05) in post-ischemic hearts. PHI also induced activating transcription factor 4 (3.5 fold, n=3, p<0.001), glucose-regulated protein 78 (6 fold, n=3, p<0.001) and ER degradation-enhancing alpha-mannosidase-like protein (2.8 fold, n=3, p<0.001) expression in reperfusing hearts. Thus PHI resulted in significant reduction of apoptosis in post-ischemic myocardium. Our studies suggest that PHI induces protective ER stress proteins and attenuates post-ischemic myocardial damage by decreasing the pro-apoptotic components of the UPR.
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PMID:Prolyl hydroxylase inhibition attenuates post-ischemic cardiac injury via induction of endoplasmic reticulum stress genes. 1952 66