Silencing of C3G increases cardiomyocyte survival inhibition and apoptosis via regulation of p‐ERK1/2 and Bax

Yang, Dongyan; Zhang, Lei; Zhang, Zhisheng; Hu, Sulei; Fu, Yanbo; Laukkanen, Jari A.; Li, Gang

doi:10.1111/1440-1681.13027

Cited by 4 publications

(16 citation statements)

References 28 publications

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“…Their specificity to detect C3G in mouse brain lysate by western blot is shown in Supplementary figure 1 A. These antibodies have been used extensively to study cellular C3G and specifically recognize C3G, and no other proteins from cell lysates 10 , 13 , 22 , 25 , 27 , 31 , 38 , 39 , 57 – 66 . As an alternate tissue type and cell line for comparison, lysates prepared from 3-months-old mouse testis and Neuro2A cells were used, which showed C3G-specific polypeptides only at 140 kDa (Fig.…”

Section: Resultsmentioning

confidence: 99%

Expression of a novel brain specific isoform of C3G is regulated during development

Sriram

Chintala

Parthasaradhi

et al. 2020

Sci Rep

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Mice lacking C3G (RapGEF1), a ubiquitously expressed protein essential for neuronal differentiation, show multiple defects in brain development. Function of C3G in neurogenesis is poorly defined. Here, we identify brain specific expression of a novel C3G isoform in mice and humans. This isoform has an insert in the Crk-binding region, generating a polypeptide of 175 kDa, unlike the previously known 140 kDa form expressed in all other tissues. In the adult mouse brain, C3G expression is seen in neurons, but was not detectable in GFAP-positive cells. C3G levels were high in the CA3 region of hippocampus and in mitral cells of olfactory bulb. Neural progenitor cells positive for Doublecortin and Nestin, show expression of C3G. During development, C3G is expressed in precursor cells prior to their differentiation into mature neurons or astrocytes. The 175 kDa as well as 140 kDa forms are seen in embryonic mouse brain, while only the 175 kDa variant is seen in post-natal brain. Human cerebral organoids generated from induced pluripotent stem cells predominantly expressed the 140 kDa polypeptides, and the 175 kDa isoform appeared upon maturation. This study describes developmental regulation and neuronal expression of a brain specific isoform of C3G, a molecule essential for normal development of the mammalian brain.

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Section: Resultsmentioning

confidence: 99%

Expression of a novel brain specific isoform of C3G is regulated during development

Sriram

Chintala

Parthasaradhi

et al. 2020

Sci Rep

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“…Total RNA was puri ed, quanti ed and reversely transcribed into cDNA as described previously [7,9]. The generated cDNA was ampli ed using speci c primers of rat C3G and GAPDH (glyceraldehyde-3phosphate dehydrogenase) genes respectively (Table 1).…”

Section: Rt-pcr Analysis For C3g Mrnamentioning

confidence: 99%

Knockdown of C3G Mitigates Post-Infarct Remodeling Via Regulation of ERK1/2, Bcl-2 and Bax in Rat Myocardial Cells

Deng

et al. 2021

Preprint

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Cardiomyocyte-specific knockout of pro-survival integrin β1 subunit and its downstream components have been demonstrated to aggravate remodeling after myocardial infarction (MI). However, as a component of integrin pathway, it is unclear whether knockdown of pro-survival C3G (rap guanine nucleotide exchange factor 1) in cardiac myocytes and fibroblasts could have effect on myocardial remodeling. A rat model of MI was established by ligation of left anterior descending coronary artery. Infarcted myocardium and its border zones in Sprague-Dawley rats were transiently infected with C3G knockout lentivirus via local injection to knockdown C3G in the myocardium. Twelve weeks after injection with the lentiviruses, cardiomyocytic apoptosis and collagen in surviving myocardium, and left ventricle (LV) end-diastolic diameter were decreased, whereas LV weight / body weight ratio and LV ejection fraction were increased in MI group via down-regulation of pro-survival C3G, phosphorylated (p) ERK1/2 (phosphorylated extracellular regulated kinase 1/2) and Bcl-2 (B-cell lymphoma-2), and up-regulation of pro-apoptotic Bax in the surviving myocardium. On the other hand, treatment with the lentiviruses was found to delete C3G and diminish cell proliferation in vitro cardiac myocytic and fibroblastic cell lines respectively via down-regulation of p-ERK1/2 and Bcl-2, and up-regulation of Bax. In conlusion, knockdown of pro-survival C3G in myocardium may mitigate surviving myocardial remodeling after MI, possibly through regulation of p-ERK1/2, Bcl-2 and Bax in vivo cardiac myocytes and fibroblasts.

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“…An equal number of the cells (1 x 10 5 ) were infected with C3G KO and NT recombinant lentiviruses respectively. The cells were divided into C3G KO and NT groups, and subjected to treatment with hypoxia [7,9]. The cells were nally randomly divided into NT, C3G KO, NT + hypoxia and C3G KO + hypoxia groups.…”

Section: Construction Of C3g Knockout Recombinant Lentivirusesmentioning

confidence: 99%

“…Seventy-two hours after infection, the apoptotic and necrotic cells were labeled respectively with annexin V uorescein isothiocyanate (FITC) and propidium iodide (PI). The labeled cells were then sorted by ow cytometry as described previously [7,9]. The cell apoptotic rates were calculated as the percentage of the number of the annexin V FITC positive and PI negative cells over the number of the total cells.…”

Section: Flow Cytometry Analysis For Cell Apoptosis In Vitromentioning

confidence: 99%

“…The effects of CrkL are inferred to be mediated by its downstream pro-survival molecules such as C3G exchange factor. In addition, C3G protein has been shown to express in vitro cardiomyocytic cell line, and its elevated expression was con rmed in the surviving myocardium after MI [7,8]; and knockdown of pro-survival C3G can aggravate H/R-induced apoptosis and pathological processes in vitro cardiomyocytic cell line [7]. However, it is still unclear whether knockdown of pro-survival C3G in myocardium may have effect on the process of surviving myocardial remodeling after MI via regulation of p-ERK1/2 (phosphorylated extracellular regulated kinase 1/2), Bcl-2 (B-cell lymphoma-2) and Bax in cardiac myocytes and broblasts.…”

Section: Introductionmentioning

confidence: 99%

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Knockdown of C3G Mitigates Post-Infarct Remodeling via Regulation of ERK1/2, Bcl-2 and Bax in Rat Myocardial Cells

Deng

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Background: Cardiomyocyte-specific knockout of pro-survival integrin β1 subunit and its downstream components have been demonstrated to aggravate remodeling after myocardial infarction (MI). However, as a component of integrin pathway, it is unclear whether knockdown of pro-survival C3G (rap guanine nucleotide exchange factor 1) in cardiac myocytes and fibroblasts could have effect on myocardial remodeling. Methods and results: A rat model of MI was established by ligation of left anterior descending coronary artery. Infarcted myocardium and its border zones in Sprague-Dawley rats were transiently infected with C3G knockout lentivirus via local injection to knockdown C3G in the myocardium. Twelve weeks after injection with the lentiviruses, cardiomyocytic apoptosis and collagen in surviving myocardium, and left ventricle (LV) end-diastolic diameter were decreased, whereas LV weight / body weight ratio and LV ejection fraction were increased in MI group via down-regulation of pro-survival C3G, phosphorylated (p) ERK1/2 (phosphorylated extracellular regulated kinase 1/2) and Bcl-2 (B-cell lymphoma-2), and up-regulation of pro-apoptotic Bax in the surviving myocardium. On the other hand, treatment with the lentiviruses was found to delete C3G and diminish cell proliferation in vitro cardiac myocytic and fibroblastic cell lines respectively via down-regulation of p-ERK1/2 and Bcl-2, and up-regulation of Bax. Conclusions: Knockdown of pro-survival C3G in myocardium may mitigate surviving myocardial remodeling after MI, possibly through regulation of p-ERK1/2, Bcl-2 and Bax in vivo cardiac myocytes and fibroblasts.

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Silencing of C3G increases cardiomyocyte survival inhibition and apoptosis via regulation of p‐ERK1/2 and Bax

Cited by 4 publications

References 28 publications

Expression of a novel brain specific isoform of C3G is regulated during development

Expression of a novel brain specific isoform of C3G is regulated during development

Knockdown of C3G Mitigates Post-Infarct Remodeling Via Regulation of ERK1/2, Bcl-2 and Bax in Rat Myocardial Cells

Knockdown of C3G Mitigates Post-Infarct Remodeling via Regulation of ERK1/2, Bcl-2 and Bax in Rat Myocardial Cells

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