Antiapoptotic Bcl-2 family proteins BCL-xL and MCL-1 integrate neural progenitor survival and proliferation during postnatal cerebellar neurogenesis

Veleta, Katherine; Cleveland, Abigail; Babcock, Benjamin; He, You–Wen; Hwang, Duhyeong; Sokolsky-Papkov, Marina; Gershon, Timothy R.

doi:10.1038/s41418-020-00687-7

Cited by 12 publications

(7 citation statements)

References 32 publications

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“…Of these, Bcl2 is an antiapoptotic molecule that inhibits cell apoptosis by reducing reactive oxygen species [38] and it has been also observed that the down-regulation of Bcl2 or over-expression of Bax can promote tumor cell apoptosis [39,40]. Bax promotes cell apoptosis by enhancing the permeability of mitochondria and mediating the synthesis of apoptotic complexes [41][42][43]. This study found that AS-IV treatment increased the ratio of Bax/Bcl-2, which further demonstrated the role of the mitochondria in AS-IV induced apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Astragaloside-IV Inhibits Pancreatic Cancer Cell Proliferation in Vitro and in Vivo by Inducing Cell Cycle Arrest and Apoptosis

Chen

Ding

Tang

et al. 2022

Preprint

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Astragaloside IV (AS-IV) or 3-O-β-D-xylopyranosyl-6-O-β-D-glucopyranosylcyl-cloastragenol is a bioactive saponin extract from the root of Astragalus membranaceus. It has been proven to have an anti-tumor effect in a variety of tumors by inducing cell apoptosis and inhibiting cell proliferation. Its effects on pancreatic cancer have not been investigated. This study investigated the effects of AS-IV on proliferation, apoptosis and migration of pancreatic cancer cells in vitro and in vivo and explored its underlying mechanism. Pancreatic cancer cell lines SW1990 and Panc-1were treated with different doses of AS-IV. Plate clonality, CCK-8, EDU and flow cytometry were used to explore the effect of AS-IV on pancreatic cancer cell proliferation and cell cycle in vitro. Wound healing was used to investigate the effects of AS-IV on pancreatic cell migration. The protein expression levels of Bax/Bcl2, caspase3/7, cyclin D1, cyclin E and CDK4 were analyzed by western blotting. The results showed that AS-IV significantly inhibited tumor cell proliferation and cell cycle, induced apoptosis both in vitro and vivo on a dose-dependent basis and significantly inhibited the growth of pancreatic cell xenograft tumor in nude mice. Wound healing assays indicated that AS-IV also inhibited the migration of pancreatic cancer cells in a dose-dependent manner. This research confirmed that AS-IV inhibited pancreatic cancer cell proliferation by blocking the cell cycle and inducing apoptosis. It was hypothesized from this experiment that the potential mechanism of AS-IV inducing apoptosis of pancreatic cancer cells may be understood by activating the Bcl2/Bax/Caspase-3/Caspase-7 signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Astragaloside-IV Inhibits Pancreatic Cancer Cell Proliferation in Vitro and in Vivo by Inducing Cell Cycle Arrest and Apoptosis

Chen

Ding

Tang

et al. 2022

Preprint

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“…To further explore the molecular mechanisms underlying the TFCJ anti-apoptosis and anti-oxidant stress effect, we detected the expression changes of mediators of apoptosis and oxidant stress involved in ischemic brain damage under the inhibitory condition of PI3K/Akt/mTOR signaling pathway. BCL-2 is a type of anti-apoptotic protein, while BAX and cleaved-Caspase-3 are known to promote apoptosis ( Veleta et al, 2020 ; Wei et al, 2020 ). The protein expression of BCL-2, BAX, and cleaved-Caspase-3 were detected by using western blot to evaluate the degree of apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Total Flavonoids of Chuju Decrease Oxidative Stress and Cell Apoptosis in Ischemic Stroke Rats: Network and Experimental Analyses

et al. 2021

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Background: Pharmacological research results showed that total flavonoids of Chuju (TFCJ) could be used to treat acute myocardial ischemia and myocardial ischemia-reperfusion injury. In this study, we explored the protective effect of TFCJ on ischemic stroke (IS) in the IS rat model. We hypothesized that TFCJ might exert its neuroprotective effects by suppressing apoptosis and oxidative stress that are closely related to PI3K/Akt/mTOR signaling pathway.Method: TFCJ (10, 20, and 40 mg/kg) was administered for 7 days. Rats (260 ± 20 g) were subjected to middle cerebral artery occlusion (MCAO) for 2 h and reperfusion for 24 h. The neuroprotective effect of TFCJ was substantiated in terms of neurological deficits, oxidative stress (superoxide dismutase, glutathione peroxidase, catalase, and malondialdehyde), pathomorphological changes (HE staining and TUNEL staining), and neurobehavioral functions in the rats. Then, we employed network pharmacology to reveal the potential mechanism of TFCJ against IS. Western blot was used to determine the levels of PI3K/AKT/mTOR pathway proteins. The expression of BCL-2, BAX, and cleaved-Caspase-3 was also measured by Western blots and RT-PCR.Results: The histopathological assessment showed that TFCJ reduced MCAO-induced brain damage. Besides, TFCJ exerted a protective role in MCAO rats by alleviating cell apoptosis and oxidative stress. Network pharmacology showed that TFCJ might be used against IS through the PI3K/AKT signaling pathway. TFCJ reduced cell apoptosis and oxidative stress by increasing the level of p-AKT and p-mTOR in MCAO rats, while the effect of TFCJ was significantly reversed when applying LY294002 (PI3k inhibitor).Conclusion: These results indicated that TFCJ might decrease oxidative stress and apoptosis that are closely related to PI3K/Akt/mTOR pathway in IS. TFCJ is a promising authentic traditional Chinese medicine for the management of IS.

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“…We investigated developmental changes in Eed cKO CGNPs, which showed the more abnormal phenotype. We quantified expression of the proliferation marker phosphorylated-RB (pRB) and the apoptotic marker cleaved Caspase-3 (cC3), as both decreased CGNP proliferation and increased CGNP apoptosis can cause cerebellar hypoplasia (13,(31)(32)(33). Eed deletion was previously shown to decrease proliferation and increased apoptosis in hippocampal progenitors (11).…”

Section: Eed Deletion Decreases Progenitor Proliferation and Increase...mentioning

confidence: 99%

PRC2 disruption in cerebellar progenitors produces cerebellar hypoplasia and aberrant myoid differentiation without blocking medulloblastoma growth

Cleveland

Malawsky

Churiwal

et al. 2022

Preprint

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We show that the Polycomb Repressive Complex 2 (PRC2) maintains neural identity in Sonic Hedgehog (SHH)-driven cerebellar granule neuron progenitors (CGNPs) and SHH-driven medulloblastoma, a cancer of CGNPs. Proliferating CGNPs and medulloblastoma cells pass the neural fate commitment to their progeny through epigenetic mechanisms. The PRC2 mediates epigenetic regulation through histone methylation, and PRC2 inhibitors have been proposed for medulloblastoma therapy. We investigated PRC2 function in CGNPs and medulloblastoma by conditionally deleting PRC2 components Eed or Ezh2 in CGNPs and analyzing cerebellar growth, cellular gene expression (scRNA-seq), and tumorigenesis in medulloblastoma-prone Smo-mutant mice. Eed-deleted CGNPs showed reduced growth, with decreased proliferation, increased apoptosis and inappropriate myoid differentiation. Ezh2-deleted CGNPs also showed myoid differentiation without reduced growth. Eed-deleted and Ezh2-deleted medulloblastomas similarly demonstrated myoid differentiation, but progressed more rapidly than PRC2-intact controls. The PRC2 thus maintained neural fate in CGNPs and medulloblastoma, but PRC2 disruption did not block SHH medulloblastoma progression.

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Antiapoptotic Bcl-2 family proteins BCL-xL and MCL-1 integrate neural progenitor survival and proliferation during postnatal cerebellar neurogenesis

Cited by 12 publications

References 32 publications

Astragaloside-IV Inhibits Pancreatic Cancer Cell Proliferation in Vitro and in Vivo by Inducing Cell Cycle Arrest and Apoptosis

Astragaloside-IV Inhibits Pancreatic Cancer Cell Proliferation in Vitro and in Vivo by Inducing Cell Cycle Arrest and Apoptosis

Total Flavonoids of Chuju Decrease Oxidative Stress and Cell Apoptosis in Ischemic Stroke Rats: Network and Experimental Analyses

PRC2 disruption in cerebellar progenitors produces cerebellar hypoplasia and aberrant myoid differentiation without blocking medulloblastoma growth

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