O-GlcNAcylation Is Essential for Autophagy in Cardiomyocytes.

Since both O-GlcNAcylation and autophagy sense intracellular nutrient level, the alteration of those two pathways plays substantial roles in the progression of heart failure. Hence, determining the relationship between O-GlcNAcylation and autophagy is imperative to understand, prevent, and treat heart failure. However, the mechanism on how O-GlcNAcylation regulates autophagy in the heart is poorly investigated. In this study, we demonstrated that O-GlcNAcylation is required for autophagy in cardiomyocytes by utilizing an O-linked ß-N-acetylglucosamine transferase (OGT) cardiomyocyte-specific knockout mouse model for the first time. We also identified that OGT might regulate the initiation of autophagy in cardiomyocytes through promoting the activity of ULK1 by O-GlcNAcylation. In conclusion, our findings provide new insights into the molecular mechanisms underlying heart dysfunction and benefit the development of treatments for heart failure.

O-linked ß-N-acetylglucosamine transferase plays an essential role in heart development through regulating angiopoietin-1.

O-linked N-acetylglucosamine (GlcNAc) transferase (OGT) is the only enzyme catalyzing O-GlcNAcylation. Although it has been shown that OGT plays an essential role in maintaining postnatal heart function, its role in heart development remains unknown. Here we showed that loss of OGT in early fetal cardiomyocytes led to multiple heart developmental defects including hypertrabeculation, biventricular dilation, atrial septal defects, ventricular septal defects, and defects in coronary vessel development. In addition, RNA sequencing revealed that Angiopoietin-1, required within cardiomyocytes for both myocardial and coronary vessel development, was dramatically downregulated in cardiomyocyte-specific OGT knockout mouse hearts. In conclusion, our data demonstrated that OGT plays an essential role in regulating heart development through activating expression of cardiomyocyte Angiopoietin-1.

Downregulation of miR-483-5p decreases hypoxia-induced injury in human cardiomyocytes by targeting MAPK3.

BACKGROUND: MiR-483-5p was recently identified as a risk factor in the early stages of acute myocardial infarction (AMI) patients. Here, we further investigated how miR-483-5p affects cardiomyocyte apoptosis and oxidative stress under hypoxic conditions. METHODS: Plasma samples were collected from AMI patients and healthy volunteers. The expression of miR-483-5p was determined using quantitative real-time PCR. An in vitro hypoxic model was constructed to mimic AMI in AC16 cells. Cell viability, apoptosis and oxidative stress biomarker levels (MDA, SOD and CAT) were respectively determined using CCK-8, flow cytometry and commercial assay kits. RESULTS: The expression levels of miR-483-5p were significantly higher in AMI patients than in control subjects. Circulating levels of miR-483-5p positively correlated with creatine kinase MB isoform (CK-MB) and cardiac troponin I (cTnI) levels. The in vitro experiments showed that the expression levels of miR-483-5p were also upregulated in hypoxia-induced AC16 cell injury. MiR-483-5p overexpression significantly increased hypoxia-induced cardiomyocyte apoptosis and oxidative stress, while knockdown attenuated these effects. Mechanistically, miR-483-5p directly targets MAPK3 in AC16 cells. Furthermore, the protective effects of miR-483-5p knockdown against hypoxia-induced cardiomyocyte injury are partially dependent on MAPK3. CONCLUSIONS: MiR-483-5p, which targets MAPK3, might be a potential therapeutic target for the diagnosis and prevention of hypoxia-induced myocardial injury.

A New Zn(II)-containing Coordination Polymer for Photocatalytic Degradation of Organic Dyes and Treatment Activity on Atherosclerosis via Reducing the Vcam-1 Expression.

By employment of a rigid tripodal nitrogen-containing heterotopic ligand tris(1-imidazolyl) benzene (Htib), a new fluorescent Zn(II)-containing coordination polymer {[Zn(tib)2](NO3)2(H2O)3}n (1) with a rare two-fold interpenetrating (3,6)-connected pyr network topology has been successfully prepared under the solvothermal reaction conditions. Under the condition of visible light irradiation, rhodamine B (RhB) and methylene blue (MB) could be degraded with good performance. In the biological function study, the cytotoxicity of the synthetic was evaluated with CCK-8 detection kit on human umbilical vein endothelial cells (HUVEC). The inhibitory effect of compound on vcam-1 expression in the vascular endothelial cells was evaluated by RT-PCR. The effect of the complex on the inflammatory response in the vascular endothelial cells was determined via ELISA test of IL-1ß and TNF-α. The results of pose scoring software as well as molecular docking was conducted to explore the interaction between compounds and VCAM, which might provide latent regulatory mechanisms along with binding sites for compounds.

Structure-Based Specific Detection and Inhibition of Monoamine Oxidases and Their Applications in Central Nervous System Diseases.

Monoamine oxidases (MAOs) are the enzymes that catalyze the oxidation of monoamines, such as dopamine, norepinephrine, and serotonin, which serve as key neurotransmitters in the central nervous system (CNS). MAOs play important roles in maintaining the homeostasis of monoamines, and the aberrant expression or activation of MAOs underlies the pathogenesis of monoamine neurotransmitter disorders, including neuropsychiatric and neurodegenerative diseases. Clearly, detecting and inhibiting the activities of MAOs is of great value for the diagnosis and therapeutics of these diseases. Accordingly, many specific detection probes and inhibitors have been developed and substantially contributed to basic and clinical studies of these diseases. In this review, progress in the detecting and inhibiting of MAOs and their applications in mechanism exploration and treatment of neurotransmitter-related disorders is summarized. Notably, how the detection probes and inhibitors of MAOs were developed has been specifically addressed. It is hoped that this review will benefit the design of more effective and sensitive probes and inhibitors for MAOs, and eventually the treatment of monoamine neurotransmitter disorders.

[Molecular mechanism of the changes in ventricular electrical remodeling caused by mechano-electrical feedback in rabbits with congestive heart failure].

This study sought to explore the relationship between the change in ventricular electrical remodeling caused by mechano-electrical feedback and the expression of L-type Ca2+ -channel and/or sarcoplasmic reticulum Ca2+ -ATPase in the rabbits with congestive heart failure (CHF). 138 rabbits were divided into two groups (CHF and control). We measured the ventricular monophasic action potential duration (MAPD) and ventricular effective refractory period (VERP) during ventricular pacing at the stimulus frequency of 220/240/260 bpm in these rabbits. Rapid atrial pacing (260/min) was given for 30 minutes. The MAPD and VERP were measured again. Then ventricular fibrillation was induced by S1S2S3 program stimulation. We extracted the total RNA from the myocardium respectively and detected L-type Ca2+ -channel mRNA and sarcoplasmic reticulum Ca2+ -ATPase mRNA by use of Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). In group CHF, with the increasing of preload/afterload, L-type Ca2+ -channel mRNA was up regulated after rapid atrial pacing when compared with that in control groups (P < 0.05). There was no significant change in sarcoplasmic reticulum Ca2+ -ATPase mRNA after rapid atrial pacing when compared with controls (P > or = 0.05). The changes in MAPD90 and VERP were related with the extent of L-type Ca2+ -channel mRNA up regulation. But the changes in MAPD90 and VERP were not significantly related with the extent of sarcoplasmic reticulum Ca2+ -ATPase mRNA up regulation. These findings suggest that Mechano-Electrical Feedback could increase the regional changes of ventricular electrical remodeling in rabbits with CHF and so to predispose them to ventricular arrhythmia. The changes may be related with the up regulation of L-type Ca2+ -channel mRNA, but not with sarcoplasmic reticulum Ca2+ -ATPase mRNA.

[Relation between insulin resistance and A1166C molecular variant of type 1 angiotensin II receptor gene in patients with coronary heart disease].

OBJECTIVE: To explore the relation between insulin resistance(IR) and A1166C molecular variant of type 1 angiotensin II receptor(AT1R) gene in Chinese subjects with coronary heart disease(CHD). METHODS: IR was calculated by 1/(fast plasma insulin x fast plasma glucose). The A1166C molecular variant of AT1R gene was determined by polymerase chain reaction and restriction endonuclease analysis methods in 90 patients with coronary heart disease and 80 healthy people. RESULTS: The frequency of allele C of group CHD was significantly higher than that of control group. There was no significant difference of IR level among AT1R A1166C AA, AC, CC genotypes in patients with CHD(P > 0.05). CONCLUSION: No significant association between A1166C molecular variant of AT1R gene and insulin resistance was found in Chinese with CHD.