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

Cao, Xiaolu; Hu, Xingjian; Hu, Jiaqing; Zheng, Wenxia

doi:10.1016/j.brainres.2011.02.016

Cited by 28 publications

(26 citation statements)

References 32 publications

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“…SRF has, indeed, different co-activators such as the ets domain-containing ternary complex factors [23] and the myocardin-related transcription factors (MRTF’s) [24] that modulate SRF activity. Although we did not analyse such co-activators, it is known that SRF-induced target gene expression increases for example by upregulation of MRTF-A expression during hypoxia and ischemia-reperfusion in cardiac cells [25] as well as in rat cortical and hippocampal neurons [26]. Of special interest is the fact that in immediate proximity of the SRF binding site there are also two SP1 binding sites.…”

Section: Discussionmentioning

confidence: 99%

An Alternative Promoter in Intron1 of the Renin Gene is Regulated by Glucose Starvation via Serum Response Factor

Lutze¹,

Wanka²,

Bäumgen³

et al. 2017

Cell Physiol Biochem

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Background/Aims: Renin is known as a secretory glycoprotein that ultimately leads to angiotensin II generation. In this way renin exerts pro-inflammatory effects and promotes cardiac injury. Additional transcripts have been identified encoding for a cytosolic renin isoform that - in contrast to secretory renin - exhibits cardioprotective effects under ischemic conditions. The promoter of these transcripts is unknown. Methods: Using qRT-PCR and dual-luciferase reporter assay we examined the expression and promotor activity of cytosolic renin as well as the regulation by glucose starvation in H9c2 cardiomyoblasts. Results: We identified a promoter in intron1 of the rat renin gene with two glucose starvation-sensitive regions. One region contains a binding motif for serum response factor (SRF). Under glucose depletion expression of SRF increased prior to cytosolic renin. SRF knock down selectively decreased cytosolic renin expression and attenuated the increase of cytosolic renin expression under glucose depletion. Conclusions: Transcripts encoding for secretory and cytosolic renin are differentially expressed. The low basal expression of cytosolic renin as well as its induction under ischemia-related conditions represents an efficient system regulated in accordance with its previously identified unfavorable effects under control situations but protective effects seen after myocardial infarction or glucose depletion.

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Section: Discussionmentioning

confidence: 99%

An Alternative Promoter in Intron1 of the Renin Gene is Regulated by Glucose Starvation via Serum Response Factor

Lutze¹,

Wanka²,

Bäumgen³

et al. 2017

Cell Physiol Biochem

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“…16,18 MYOCD is a key regulator of cardiovascular myogenic development 16,19,20 and acts as a nuclear transcription cofactor for myogenic genes, as well as genes involved in muscle regeneration and protection against apoptosis. 21,22 Telomerase maintains telomere length, contributes to cell survival and proliferation, and prevents cellular senescence. 23, 24 We have shown that AT-MSCs that coexpress TERT and MYOCD have increased endogenous levels of octamer-binding transcription factor 4, MYOCD, myocyte-specific enhancer factor 2c, and homeobox protein NKx2.5.…”

mentioning

confidence: 99%

Transplantation of Mesenchymal Cells Rejuvenated by the Overexpression of Telomerase and Myocardin Promotes Revascularization and Tissue Repair in a Murine Model of Hindlimb Ischemia

Madonna

Taylor

Geng

et al. 2013

Circulation Research

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Rationale: The number and function of stem cells decline with aging, reducing the ability of stem cells to contribute to endogenous repair processes. The repair capacity of stem cells in older individuals may be improved by genetically reprogramming the stem cells to exhibit delayed senescence and enhanced regenerative properties. Objective: We examined whether the overexpression of myocardin (MYOCD) and telomerase reverse transcriptase (TERT) enhanced the survival, growth, and myogenic differentiation of mesenchymal stromal cells (MSCs) isolated from adipose or bone marrow tissues of aged mice. We also examined the therapeutic efficacy of transplanted MSCs overexpressing MYOCD and TERT in a murine model of hindlimb ischemia. Methods and Results: MSCs from adipose or bone marrow tissues of young (1 month old) and aged (12 months old) male C57BL/6 and apolipoprotein E–null mice were transiently transduced with lentiviral vectors encoding TERT, MYOCD, or both TERT and MYOCD. Flow cytometry and bromodeoxyuridine cell proliferation assays showed that transduction with TERT and, to a lesser extent, MYOCD, increased MSC viability and proliferation. In colony-forming assays, MSCs overexpressing TERT and MYOCD were more clonogenic than mock-transduced MSCs. Fas-induced apoptosis was inhibited in MSCs overexpressing MYOCD or TERT. When compared with aged mock-transduced MSCs, aged MSCs overexpressing TERT, MYOCD, or both TERT and MYOCD increased myogenic marker expression, blood flow, and arteriogenesis when transplanted into the ischemic hindlimbs of apolipoprotein E–null mice. Conclusions: The delivery of the TERT and MYOCD genes into MSCs may have therapeutic applications for restoring, or rejuvenating, aged MSCs from adipose and bone marrow tissues.

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“…Extensive studies have been carried out to characterize the molecular mechanism of MRTF-A regulates Mcl-1, Bcl-2 and Arc expression [17]. As expect, the increasing of Bcl-2, Mcl-1 and Arc mRNA and protein levels induced by nebracetam was weakened when cotransfected with MRTF-A siRNA ( Figure 4).…”

Section: Nebracetam Upregulating the Transactivity And Expression Of mentioning

confidence: 73%

“…Our previous study [17] has shown that MRTF-A, as a cotranscription factory of SRF, plays an important role in promoting neuronal survival against apoptosis, which is dependent on the binding of SRF and CArG boxes located on anti-apoptosis related gene (such as Mcl-1 and Bcl-2). To determine the exact role of MRTF-A in the effect of nebracetam on Aβ25-35-induced hippocampus neuron apoptosis, we knocked down hippocampus neuronal MRTF-A using MRTF-A siRNAs.…”

Section: Mrtf-a Involved In Nebracetam Inhibiting Aβ25-35 Induced Hipmentioning

confidence: 99%

Nebracetam Inhibited Hippocampus Neurons Injury Induced by Aβ25-35 in MRTF-A-CArG Manner via ERK1/2 Pathway

Yin¹,

Cao²

2015

Mol Biol

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Nebracetam has been recently proposed to have a neuroprotective action and cognitive enhancing effect being characteristic of a nootropic drug, while the mechanisms remained ambiguity. In this study, we investigated the protective effects of nebracetam on hippocampus neurons injury-induced by β-amyloid protein(Aβ25-35)and its mechanisms. Hippocampus neurons were treated with nebracetam (0.05 mM, 0.2 mM or 0.8 mM) or Aβ25-35 (20 uM/L). We found that Nebracetam significantly reduced apoptotic induced by Aβ25-35 and increase in the total number of dendritic spines and dendritic spine density in a dose-dependent manner. RT-PCR assay and Western blotting analysis revealed that nebracetam increased the expressions of myeloid cell leukemia-1 (Mcl-1), B-cell lymphoma-2 (Bcl-2) and activity regulated cytoskeleton associated protein (Arc) in Aβ25-35-treated hippocampus neurons. Cotreatment nebracetam with MRTF-A (Myocardin-related transcription factor-A) siRNA reversed Mcl-1, Bcl-2 and Arc mRNA and protein levels. What's more, the luciferase assays indicated that the transcriptional activities of Mcl-1, Bcl-2 and Arc genes were significantly abolished by MRTF-A siRNA while it showed no changes on activities of mut Mcl-1-promoter-luc, mut Bcl-2-promoter-luc and mut Arc-promoter-luc. Additionally, the up-regulation of Mcl-1, Bcl-2 and Arc protein expressions in nebracetam-treated group was inhibited by extracellular signal regulated protein kinase 1/2 (ERK1/2) inhibitor PH98059. These results demonstrated that nebracetam inhibited Aβ25-35-induced hippocampus neurons injury by enhancing the transactivity of Mcl-1, Bcl-2 and Arc, which may actively based in MRTF-A-CArGdependent manner by thwarting the ERK1/2 pathway.

show abstract

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

Cited by 28 publications

References 32 publications

An Alternative Promoter in Intron1 of the Renin Gene is Regulated by Glucose Starvation via Serum Response Factor

An Alternative Promoter in Intron1 of the Renin Gene is Regulated by Glucose Starvation via Serum Response Factor

Transplantation of Mesenchymal Cells Rejuvenated by the Overexpression of Telomerase and Myocardin Promotes Revascularization and Tissue Repair in a Murine Model of Hindlimb Ischemia

Nebracetam Inhibited Hippocampus Neurons Injury Induced by Aβ25-35 in MRTF-A-CArG Manner via ERK1/2 Pathway

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