Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proto-oncogene (c-fos, c-jun) and nuclear factor-kappa B (NF-kappaB) expression, as well as DNA synthesis, in aortic and cerebral vascular smooth muscle cells (VSMCs) were upregulated by a decrease in extracellular magnesium ions ([Mg2+]o). Upregulation of these transcriptional factors was inversely proportional to the [Mg2+]o and occurred over the pathophysiologic range of serum Mg2+ found in patients presenting with hypertension, ischemic heart disease, and stroke. Removal of extracellular Ca2+ ([Ca2+]o), use of nifedipine or protein kinase C (PKC) inhibitors prevented the upregulation of the proto-oncogenes and DNA synthesis in VSMCs. These data show that [Mg2+]o may be an important, heretofore, overlooked natural modulator of proto-oncogene and NF-kappaB expression in VSMCs and that Ca2+ and PKC may play critical roles in induction of c-fos and c-jun in VSMCs induced by a decrease in [Mg2+]o. These results point to a role for low serum Mg2+ in potential development of hypertension, atherogenesis, vascular disease, and stroke.
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PMID:Expression of the nuclear factor-kappaB and proto-oncogenes c-fos and c-jun are induced by low extracellular Mg2+ in aortic and cerebral vascular smooth muscle cells: possible links to hypertension, atherogenesis, and stroke. 1294 25

Myocardial ischemia-reperfusion (I/R) injury is thought to have its detrimental role in coronary heart disease (CHD), which is considered as the foremost cause of death all over the world. However, molecular mechanism in the progression of myocardial I/R injury is still unclear. The goal of this study was to investigate the expression and function of microRNA-140 (miR-140) in the process of myocardial I/R injury. The miR-140 expression level was analyzed in the myocardium with I/R injury and control myocardium using quantitative real-time polymerase chain reaction. Then the relation between the level of miR-140 and YES proto-oncogene 1 (YES1) was also investigated via luciferase reporter assay. Assessment of myocardial infarct size measurement of serum myocardial enzymes and electron microscopy analysis were used for analyzing the effect of miR-140 on myocardial I/R injury. We also used Western blot analysis to examine the expression levels of the mitochondrial fission-related proteins, Drp1 and Fis1. miR-140 is downregulated, and YES1 is upregulated after myocardial I/R injury. Overexpression of miR-140 could reduce the increase related to myocardial I/R injury in infarct size and myocardial enzymes, and it also could inhibit the expression of proteins related to mitochondrial morphology and myocardial I/R-induced mitochondrial apoptosis by targeting YES1. Taken together, these findings may provide a novel insight into the molecular mechanism of miR-140 and YES1 in the progression of myocardial I/R injury. MiR-140 might become a promising therapeutic target for treating myocardial I/R injury.
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PMID:MicroRNA-140 attenuates myocardial ischemia-reperfusion injury through suppressing mitochondria-mediated apoptosis by targeting YES1. 3025 97

Objective To observe the effects of electroacupuncture (EA) at Neiguan (PC6) on protein expressions of proto-oncogene serine/threonine-protein kinase-1 ( Raf-1 ) , phospho-extracellular signal-regulated kinase 1/2 (p-ERK 1/2), and extracellular signal-regulated kinase 1/2 (ERK 1/2) in rats with myocardial hypertrophy. Methods Totally 40 healthy Sprague-Dawley (SD) rats of clean grade were divided into 4 groups according to random digit table, i.e., the normal group, the model group, the electroa- cupuncture (EA) group, the sham-EA group, 10 in each group. Rats in the normal group were fed with reg- ular forage. Left ventricular myocardial hypertrophy model was established in rats of the rest 3 groups by subcutaneously injecting isoprinosine hydrochloride (ISO) (at the daily dose of 3 mg/kg) from the nape for a total of 14 days. Rats in the EA group were needed at Neiguan (PC6) using continuous wave (2 Hz, 1 mA, 20-min switching, once per day for 14 days). Rats in the sham-EA group were needled at non-acu- points [5 mm from Neiguan (PC6)] in the same intervention method as the EA group. After intervention ECG was observed and body weight weighed in all rats. Their hearts were removed by open heart surgery and weighed after anesthesia, and then left ventricle were separated and weighed. At last heart weight index (HWI) and left ventricular weight index (LVWI) were calculated. Protein contents of Raf-1 , p-ERK 1/2, and ERK 1/2 in left ventricular myocardial tissue were detected by Western blot. Results Compared with the normal group, elevated ST-segment amplitude, HWI, LVWI, protein expressions of Raf-1 and p-ERK 1/2 were significantly higher in the model group with statistical significance (P <0. 01). Compared with the model group and the sham-EA group, elevated ST-segment amplitude, HWI, LVWI, protein expressions of Raf-1 and p-ERK 1/2 were significantly lower in the EA group with statistical significance (P <0. 05). Conclusion EA could effectively regulate myocardial ischemia in myocardial hypertrophy rats, reduce heart index, and lower protein expressions of Raf-1 and p-ERK 1/2, which might be one of signal regulating mechanisms for EA improving myocardial hypertrophy through Raf/MEK/ERK pathways.
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PMID:[Effects of Electroacupuncture at Neiguan (PC6) on Protein Expressions of Raf-1, ERK 1/2, and p-ERK 1/2 of Rats with Myocardial Hypertrophy]. 3064 27

CLU4A is identified as a proto-oncogene in various human cancers. CLU4A was reported to be up-regulated in myocardial ischemia/reperfusion injury, but the precise role of CLU4A played in myocardial ischemia/reperfusion injury remains unknown; and the underlying mechanism of CLU4A in myocardial ischemia/reperfusion injury needs to be investigated. CLU4A expression was measured after myocardial ischemia/reperfusion in mice and in H9C2 cells with hypoxia/reoxygenation treatment by q-PCR and western blotting. The cardioprotective effect of CLU4A inhibition was detected by monitoring the cell viability, cell apoptosis, and LDH activity in vitro and in vivo, and examining the infarct size and cardiac function in vivo. The molecular mechanism was further determined by examining the effects of PD98059, a specific inhibitor of the ERK signaling pathways in H9C2 cells with hypoxia/reoxygenation treatment. CLU4A expression was up-regulated after myocardial ischemia/reperfusion in mice and in H9C2 cells with hypoxia/reoxygenation treatment. Inhibition of CLU4A improved the cell viability, restrained the cell apoptosis, and suppressed LDH activity in vitro. Consistently, knockdown of CLU4A reduced the myocardial infarct size and improved cardiac function in vivo. si-CLU4A treatment increased phosphorylated ERK (p-ERK) in vitro, but the protection role of si-CLU4A was abolished by the ERK inhibitor, PD98059. In conclusion, CLU4A expression was up-regulated in myocardial ischemia/reperfusion. Inhibition of CLU4A exhibited a cardioprotective role by an ERK-dependent pathway.
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PMID:Inhibition of CLU4A exhibits a cardioprotective role in hypoxia/reoxygenation-induced injury by an ERK-dependent pathway. 3193 38