Mitochondrial creatine kinase 1 in non-small cell lung cancer progression and hypoxia adaptation

Background Hypoxia is a prominent feature of solid cancer. This research aims to expose the role of mitochondrial creatine kinase 1 (CKMT1) in non-small cell lung cancer (NSCLC) progression and hypoxia adaptation. Methods The mRNA and protein expression of CKMT1 in NSCLC tissues were detected by using GEPIA web, immunohistochemistry and qRT-PCR. For hypoxia, cells were exposed to the 1% O2 atmosphere. The protein levels of HIF-1α and CKMT1 in H1650 and H1299 cells exposed to hypoxia were determined by western blot. The roles of CKMT1 on the proliferation, invasion and hypoxia adaptation of NSCLC cells were measured by CCK8, colony formation and transwell assays. Luciferase activity assay and HIF1 specific inhibitor (LW6) assay indicated the related function of hypoxia and CKMT1. Results CKMT1 was highly expressed in NSCLC tissues, and the high level of CKMT1 was significantly correlated with the high pathological grade of NSCLC. Knockdown of CKMT1 inhibited the cell proliferation and invasion of H1650 and H1299 cells, which could be rescued by hypoxia. Hypoxia induced the accumulation of HIF-1α and the expression of CKMT1 in H1650 and H1299 cells. Furthermore, HIF-1 as a transcription factor of CKMT1, could up-regulated the expression of CKMT1 under hypoxia. Conclusions In summary, CKMT1 has the potential as a target for NSCLC hypoxic targeted therapy.

Accumulation of Carbonyl Proteins in the Brain of Mouse Model for Methylglyoxal Detoxification Deficits

Recent studies have shown that carbonyl stress is a causative factor of schizophrenia, categorized as carbonyl stress-related schizophrenia (CS-SCZ). However, the correlation between carbonyl stress and the pathogenesis of this disease is not well established. In this study, glyoxalase 1(Glo1)-knockout and vitamin B6-deficient mice (KO/VB6 (-) mice), which are susceptible to methylglyoxal (MGO)-induced oxidative damages, were used as a CS-SCZ model to analyze MGO-modified protein and the carbonyl stress status in the brain. A comparison between Wild/VB6(+) mice and KO/VB6(−) mice for accumulated carbonyl proteins levels, with several advanced glycation end products (AGEs) in the brain, revealed that carbonyl protein levels with the Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl) ornithine (MG-H1) moiety were significantly increased in the hippocampus, prefrontal cortex, striatum, cerebral cortex, and brainstem regions of the brain in KO/VB6(−) mice. Moreover, two-dimensional electrophoresis and Liquid chromatography-tandem mass spectrometry analysis showed MG-H1-modified arginine residues in mitochondrial creatine kinase, beta-adrenergic receptor kinase 1, and T-complex protein in the hippocampus region of KO/VB6(−) mice, but not in Wild/VB6(+) mice. In particular, MG-H1 modification of mitochondrial creatine kinase was quite notable. These results suggest that further studies focusing on MG-H1-modified and accumulated proteins in the hippocampus may reveal the onset mechanism of CS-SCZ induced by MGO-induced oxidative damages.

Mitochondrial creatine kinase 1 in non-small cell lung cancer progression and hypoxia adaptation

Background Hypoxia is a prominent feature of solid cancer. This research aims to expose the role of mitochondrial creatine kinase 1 (CKMT1) in non-small cell lung cancer (NSCLC) progression and hypoxia adaptation. Methods The mRNA and protein expression of CKMT1 in NSCLC tissues and cells were detected using GEPIA web, immunohistochemistry, qRT-PCR and western blot. Cells were exposed to a hypoxic chamber with atmosphere containing 5% CO2, 1% O2 and residual N2. The protein levels of HIF-1α and CKMT1 in H1650 and H1299 cells exposed to hypoxia were determined by western blot. Luciferase activity assay and HIF1 specific inhibitor (LW6) assay indicated the related function of HIF-1 and CKMT1. The role of CKMT1 to NSCLC cells biological function on hypoxic condition was measured by CCK8, colony formation, transwell and apoptosis assay. Results CKMT1 was highly expressed in NSCLC tissues and cells using GEPIA web, immunohistochemistry, qRT-PCR and western blot. Hypoxia induced the accumulation of HIF-1α and the expression of CKMT1 in H1650 and H1299 cells. The results of luciferase activity assay and HIF1 specific inhibitor (LW6) assay indicated that HIF-1, as a transcription factor of CKMT1, up-regulated the expression of CKMT1 under hypoxic conditions. Further, knockdown of CKMT1 inhibited the cell proliferation and invasion of H1650 and H1299 cells, which could be rescued by hypoxia. Conclusions In summary, CKMT1 has the potential as a target for NSCLC hypoxic targeted therapy.

Nanocapsules With Naringin And Naringenin Affect Hepatic and Renal Energy Metabolism Without Altering Serum Markers of Toxicity in Rats

Naringin and naringenin are flavonoids found in citrus fruits and have several health benefits, however these compounds are susceptible to degradation, limiting their therapeutic application. To solve this problem, an alternative is to incorporate them into nanocapsules. The aim of this work was to evaluate the toxicity of these nanocapsules against renal and hepatic serum markers and also on the activities of pyruvate kinase, Mg2+-ATPase, and creatine kinase. Nanocapsules containing naringin and naringenin, nanocapsules without the active compounds and the compounds in their free form were administered orally, once a day, for 28 days. After treatment, the serum levels of hepatic and renal markers were not altered, nor the activities of pyruvate kinase tissue, however, the treatment of nanocapsules with flavonoids increased the activities of mitochondrial creatine kinase in the kidney and hepatic Mg2+-ATPase. Thus, renal and hepatic serum markers, which are normally used as indicators of toxicity, did not change after the period of administration of the nanoparticles. However, the activities of important enzymes of the energy metabolism in these organs were affected. Our findings reinforce that nanomaterial testing for toxicity needs to go beyond traditional methods to ensure the safe use of nanoparticles for therapeutic purposes.