Myocardin-related transcription factor-A promoting neuronal survival against apoptosis induced by hypoxia/ischemia

Abstract As therapeutic hypothermia is only partially protective for neonatal encephalopathy, safe and effective adjunct therapies are urgently needed. Melatonin and erythropoietin show promise as safe and effective neuroprotective therapies. We hypothesized that melatonin and erythropoietin individually augment 12-hour hypothermia (double therapies) and hypothermia + melatonin + erythropoietin (triple therapy) leads to optimal brain protection. Following carotid artery occlusion and hypoxia, 49 male piglets (<48 hours old) were randomized to: (i) hypothermia + vehicle (n = 12), (ii) hypothermia + melatonin (20 mg/kg over 2 hours) (n = 12), (iii) hypothermia + erythropoietin (3000 U/kg bolus) (n = 13) or (iv) triple therapy (n = 12). Melatonin, erythropoietin or vehicle were given at 1, 24 and 48 hours after hypoxia-ischemia. Hypoxia-ischemia severity was similar across groups. Therapeutic levels were achieved 3 hours after hypoxia-ischemia for melatonin (15-30mg/L) and within 30 minutes of erythropoietin administration (maximum concentration 10,000 mU/mL). Compared to hypothermia + vehicle, we observed faster amplitude integrated EEG recovery from 25-30 hours with hypothermia + melatonin (p = 0.02) and hypothermia + erythropoietin (p = 0.033) and from 55-60 hours with triple therapy (p = 0.042). Magnetic Resonance Spectroscopy Lactate/N-acetyl aspartate peak ratio was lower at 66 hours in hypothermia + melatonin (p = 0.012) and triple therapy (p = 0.032). With hypothermia + melatonin, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelled-positive cells were reduced in sensorimotor cortex (p = 0.017) and oligodendrocyte transcription factor 2 labelled-positive counts increased in hippocampus (p = 0.014) and periventricular white matter (p = 0.039). There was no reduction in terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelled-positive cells with hypothermia + erythropoietin, but increased oligodendrocyte transcription factor 2 labelled-positive cells in 5 of 8 brain regions (p < 0.05). Overall, melatonin and erythropoietin were safe and effective adjunct therapies to hypothermia. Hypothermia + melatonin double therapy led to faster amplitude integrated EEG recovery, amelioration of Lactate/N-acetyl aspartate rise and reduction in terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelled-positive cells in the sensorimotor cortex. Hypothermia + erythropoietin double therapy was association with EEG recovery and was most effective in promoting oligodendrocyte survival. Triple therapy provided no added benefit over the double therapies in this 72-hour study. Melatonin and erythropoietin influenced cell death and oligodendrocyte survival differently, reflecting distinct neuroprotective mechanisms which may become more visible with longer term studies. Staggering the administration of therapies with early melatonin and later erythropoietin (after hypothermia) may provide better protection; each therapy has complementary actions which may be time critical during the neurotoxic cascade after hypoxia-ischemia.

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Detection of deleted in malignant brain tumors 1 and runt-related transcription factor 3 gene expressions in bladder carcinoma

Molecular Biology Reports ◽

10.1007/s11033-011-1261-9 ◽

2011 ◽

Vol 39 (4) ◽

pp. 4691-4695 ◽

Cited By ~ 4

Author(s):

Yavuz Dodurga ◽

Çığır Biray Avcı ◽

N. Lale Satiroglu-Tufan ◽

Canten Tataroglu ◽

Zehra Kesen ◽

...

Keyword(s):

Transcription Factor ◽

Brain Tumors ◽

Bladder Carcinoma ◽

Gene Expressions ◽

Malignant Brain Tumors ◽

Related Transcription Factor ◽

Transcription Factor 3

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Synergistic attenuation of ovariectomy-induced bone loss by combined use of fish oil and 17β-oestradiol

British Journal Of Nutrition ◽

10.1017/s0007114517000344 ◽

2017 ◽

Vol 117 (4) ◽

pp. 479-489 ◽

Cited By ~ 4

Author(s):

Youri Jin ◽

Myoungsook Lee ◽

Yongsoon Park

Keyword(s):

Transcription Factor ◽

Bone Loss ◽

Protective Efficacy ◽

Recovery Period ◽

Serum Levels ◽

Protective Mechanism ◽

Beneficial Effects ◽

Combined Use ◽

Related Transcription Factor ◽

Turnover Markers

AbstractOestrogen and n-3 PUFA, especially EPA and DHA, have been reported to have beneficial effects on bone loss. Thus, the purpose of the present study was to investigate the synergistic bone-protective mechanism of combined treatments of EPA+DHA supplementation and oestrogen injection in ovariectomised rats. Rats were fed a modified American Institute of Nutrition-93G diet with 0 %, 1 % or 2 % n-3 PUFA (EPA+DHA) relative to the total energy intake for 12 weeks. Rats were surgically ovariectomised at week 8, and after a 1-week recovery period rats were injected with either 17β-oestradiol-3-benzoate (E2) or maize oil for the last 3 weeks. Combined use of n-3 PUFA and E2 synergistically increased femoral cortical bone volume, bone mineral content and the bone expression of runt-related transcription factor 2 (RUNX2), but decreased the bone expression of IL-1β. Both n-3 PUFA and E2 decreased the bone expressions of IL-7, TNF-α and PPAR-γ, and increased the bone expression of oestrogen receptor-α. n-3 PUFA in the presence of E2 and E2 alone significantly decreased the bone expressions of IL-1β and IL-6 and increased the bone expression of RUNX2. E2 significantly decreased the serum levels of bone turnover markers and the bone expression of receptor activator of NF-κB ligand, but decreased the bone expression of osteoprotegerin. The combined use of n-3 PUFA and E2 exerted synergistic bone-protective efficacy through up-regulation of RUNX2, an essential transcription factor for bone formation, as well as the suppression of bone-resorbing cytokine IL-1β.

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Alteration in the expression of MGMT and RUNX3 due to non-CpG promoter methylation and their correlation with different risk factors in esophageal cancer patients

Tumor Biology ◽

10.1177/1010428317701630 ◽

2017 ◽

Vol 39 (5) ◽

pp. 101042831770163 ◽

Cited By ~ 5

Author(s):

Snigdha Saikia ◽

Asad Ur Rehman ◽

Prajjalendra Barooah ◽

Preeti Sarmah ◽

Mallika Bhattacharyya ◽

...

Keyword(s):

Esophageal Cancer ◽

Transcription Factor ◽

Promoter Methylation ◽

Messenger Rna ◽

Dna Methyltransferase ◽

Rna Expression ◽

Betel Nut ◽

Methylguanine Dna Methyltransferase ◽

Related Transcription Factor ◽

Transcription Factor 3

Promoter methylation reflects in the inactivation of different genes like O6-methylguanine-DNA methyltransferase DNA repair gene and runt-related transcription factor 3, a known tumor suppressor gene in various cancers such as esophageal cancer. The promoter methylation was evaluated for O6-methylguanine-DNA methyltransferase and runt-related transcription factor 3 in CpG, CHH, and CHG context (where H is A, T, or C) by next-generation sequencing. The methylation status was correlated with quantitative messenger RNA expression. In addition, messenger RNA expression was correlated with different risk factors like tobacco, alcohol, betel nut consumption, and smoking habit. CpG methylation of O6-methylguanine-DNA methyltransferase promoter had a positive association in the development of esophageal cancer (p < 0.05), whereas runt-related transcription factor 3 promoter methylation showed no significant association (p = 1.0) to develop esophageal cancer. However, the non-CpG methylation, CHH, and CHG were significantly correlated with O6-methylguanine-DNA methyltransferase (p < 0.05) and runt-related transcription factor 3 (p < 0.05) promoters in the development of esophageal cancer. The number of cytosine converted to thymine (C→T) in O6-methylguanine-DNA methyltransferase promoter showed a significant correlation between cases and controls (p < 0.05), but in runt-related transcription factor 3 no such significant correlation was observed. Besides, messenger RNA expression was found to be significantly correlated with promoter hypermethylation of O6-methylguanine-DNA methyltransferase and runt-related transcription factor 3 in the context of CHG and CHH (p < 0.05). The CpG hypermethylation in O6-methylguanine-DNA methyltransferase showed positive (p < 0.05) association, whereas in runt-related transcription factor 3, it showed contrasting negative association (p = 0.23) with their messenger RNA expression. Tobacco, betel nut consumption, and smoking habits were associated with altered messenger RNA expression of O6-methylguanine-DNA methyltransferase (p < 0.05) and betel nut consumption and smoking habits were associated with runt-related transcription factor 3 (p < 0.05). There was no significant association between messenger RNA expression of O6-methylguanine-DNA methyltransferase and runt-related transcription factor 3 with alcohol consumption (p = 0.32 and p = 0.15). In conclusion, our results suggest that an aberrant messenger RNA expression may be the outcome of CpG, CHG, and CHH methylation in O6-methylguanine-DNA methyltransferase, whereas outcome of CHG and CHH methylation in runt-related transcription factor 3 promoters along with risk factors such as consumption of tobacco, betel nut, and smoking habits in esophageal cancer from Northeast India.

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