A protein TRAP : The in vivo photocrosslinking of TRAP after its intracellular targeting to a binding sequence on the bait protein stabilizes protein interactions. Because the crosslinker is releasable, simple mass spectrometry can be used to identify the protein binding sites after purification.
Increased proliferation of pulmonary arterial smooth muscle cells (PASMCs) in response to chronic hypoxia contributes to pulmonary vascular remodeling in pulmonary hypertension (PH). PH shares numerous similarities with cancer, including a metabolic shift towards glycolysis. In lung cancer, adenylate kinase 4 (AK4) promotes metabolic reprogramming and metastasis. Against this background, we show that AK4 regulates cell proliferation and energy metabolism of primary human PASMCs. We demonstrate that chronic hypoxia upregulates AK4 in PASMCs in a hypoxia-inducible factor-1α (HIF-1α)-dependent manner. RNA interference of AK4 decreases the viability and proliferation of PASMCs under both normoxia and chronic hypoxia. AK4 silencing in PASMCs augments mitochondrial respiration and reduces glycolytic metabolism. The observed effects are associated with reduced levels of phosphorylated protein kinase B (Akt) as well as HIF-1α, indicating the existence of an AK4-HIF-1α feedforward loop in hypoxic PASMCs. Finally, we show that AK4 levels are elevated in pulmonary vessels from patients with idiopathic pulmonary arterial hypertension (IPAH), and AK4 silencing decreases glycolytic metabolism of IPAH-PASMCs. We conclude that AK4 is a new metabolic regulator in PASMCs interacting with HIF-1α and Akt signaling pathways to drive the pro-proliferative and glycolytic phenotype of PH. 相似文献
The significant expenditures for organic synthesis of high-energy materials necessitate an a priori evaluation of prospects for physical-chemical parameters. The most important of these parameters is the heat of formation characterizing this or the other compound suggested for synthesis. This study describes and analyzes the most well-known and widely used schemes and methods for evaluating and predicting the energy capacity of high-energetic materials. The accuracy of calculations is evaluated for different schemes; the limits of their applicability are determined. 相似文献
The analysis of “Quantitative Structure-Property Relationship”(QSPR), concerning the heat of formation in the condensed state, is performed for non-aromatic polynitrocompounds. The QSPR approach and our original computer program “EMMA”(Efficient Modelling of Molecular Activity) are used. This approach is based on the construction of optimal linear regression models involving physical-chemical, topological, informational, and substructural indices; it can be used as an alternative to traditional additive schemes for evaluating physical-chemical characteristics of energetic materials. On the basis of the QSPR method, the “structure-heat of formation (ΔH°f)” relationship is revealed for a data base of non-aromatic polynitrocompounds, and ΔH°f is predicted for some hypothetic substances. 相似文献
Magnetic and relativistic effects in uranium catalysts, the movement of charged particles under the effect of a uniform electric field and uniform magnetic field were studied in the paper. We have considered various mechanisms oscillating reactions (Models Jabotinsky-Korzukhina, Brusselator, Oregonator and Advanced Oregonator). The mechanisms of the motion of charged particles under the influence of an electric field and a uniform magnetic field were proposed. 相似文献