Overexpression of adrenomedullin protects mesenchymal stem cells against hypoxia and serum deprivation‑induced apoptosis via the Akt/GSK3β and Bcl‑2 signaling pathways

Si, Hongjin; Zhang, Yao; Song, Yuqing; Li, Lili

doi:10.3892/ijmm.2018.3533

Cited by 20 publications

(19 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As is known, AKT substrate GSK3β is negatively modulated by AKT activity, while activated GSK3β-Ser9 (non-phosphorylated state) is reported to regulate cell cycle analysis and apoptosis [38][39][40]. In our research, we also analyzed the effects of LF-MF on the activities of GSK3β in MCF-7 and ZR-75-1 cells.…”

Section: Discussionmentioning

confidence: 91%

Low-Frequency Magnetic Fields (LF-MFs) Inhibit Proliferation by Triggering Apoptosis and Altering Cell Cycle Distribution in Breast Cancer Cells

Wang

Lin

2020

IJMS

View full text Add to dashboard Cite

Breast cancer is a common malignancy threatening women's health around the world. Despite improved treatments for different subtypes of breast tumors that have been put forward, there still exists a poor therapeutic response and prognosis. Magnetic fields, as a non-invasive therapy, have shown anti-tumor effects in vitro and in vivo; however, the detailed mechanisms involved are still not clear. In this study, we found that in exposure to low-frequency magnetic fields (LF-MFs) with an intensity of 1 mT and frequencies of 50, 125, 200, and 275 Hz, separately, the proliferation of breast cancer cells was inhibited and LF-MF with 200 Hz reached the optimum inhibition effect, on exposure time-dependently. Notably, we found that exposure to LF-MF led to MCF-7 and ZR-75-1 cell apoptosis and cell cycle arrest. Moreover, we also discovered that LF-MF effectively increased the level of reactive oxygen species (ROS), suppressed the PI3K/AKT signaling pathway, and activated glycogen synthase kinase-3β (GSK-3β). We demonstrated that the GSK3β activity contributed to LF-MF-induced cell proliferation inhibition and apoptosis, while the underlying mechanism was associated with the inhibition of PI3K/AKT through increasing the intracellular ROS accumulation. These results indicate that LF-MF with a specific frequency may be an attractive therapy to treat breast cancers.Int. J. Mol. Sci. 2020, 21, 2952 2 of 14 processes [9]. Further research has found that low-frequency magnetic fields (LF-MFs), namely, those with a frequency below 300 Hz, possess a variety of effects such as the regulation of immunity [10] and inflammation [11], suppression of angiogenesis [12], contribution to differentiation [13], and induced apoptosis [14]. Although many biological effects of magnetic fields have been reported, the mechanisms involved still remain unclear.Reactive oxygen species (ROS), including superoxide and hydrogen peroxide, are one of the main causes of tumors and play an important role in the process of tumor progression, metastasis and apoptosis [15]. Low-frequency magnetic fields have been demonstrated to significantly increase the intracellular ROS levels in many kinds of cells [16]. The PI3K/AKT pathway is a pivotal signaling pathway, which is closely related to the regulation of cell survival, apoptosis, migration and proliferation [17]. The relationship between ROS and the PI3K/AKT pathway in apoptosis regulation has been confirmed in several studies [18,19]. Glycogen synthase kinase-3β (GSK-3β) is an effector of PI3K/AKT, and is a kind of serine / threonine protein kinase, whose biological function is far beyond the glucose synthesis-regulating enzyme it was initially considered. GSK-3β can phosphorylate many substrates, including metabolism and signal protein, transcription factors of cell structural protein, etc., playing an important role in the process of tumor occurrence and development [20,21]. Baihuan Feng et al. reported that exposure to 50 Hz-0.4 mT MF affected mitochondrial permeability by the ROS-regulating phosphoryla...

show abstract

Section: Discussionmentioning

confidence: 91%

Low-Frequency Magnetic Fields (LF-MFs) Inhibit Proliferation by Triggering Apoptosis and Altering Cell Cycle Distribution in Breast Cancer Cells

Wang

Lin

2020

IJMS

View full text Add to dashboard Cite

show abstract

“…AM was found an anti-apoptotic agent in human fibroblast-like synoviocytes and a murine osteoblastic cell line and in articular cartilage from CIA mice 8 , 13 , 17 . In many cell types, AM has also been found a critical regulator of cell survival in physiologic and pathologic environments 22 – 25 . To our knowledge, this paper is the first to show that AM inhibits Fas-induced apoptosis in BACs under hypoxia.…”

Section: Discussionmentioning

confidence: 99%

“…In such an environment, AM production and activity could be enhanced in several cell types 23 – 25 , especially in endothelial cells, where CLR and AM levels were increased in response to hypoxic stress, thereby suggesting a regulatory loop to favour the proangiogenic effect of AM 7 , 30 . Of interest, patients with OA showed elevated levels of circulating AM, with a direct correlation with the severity of joint damage 31 .…”

Section: Discussionmentioning

confidence: 99%

Adrenomedullin and truncated peptide adrenomedullin(22-52) affect chondrocyte response to apoptotis in vitro: downregulation of FAS protects chondrocyte from cell death

Velard

Chatron-Colliet

Côme

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Chondrocyte apoptosis may have a pivotal role in the development of osteoarthritis. Interest has increased in the use of anti-apoptotic compounds to protect against osteoarthritis development. In this work, we investigated the effect of adrenomedullin (AM), a 52 amino-acid hormone peptide, and a 31 amino-acid truncated form, AM(22-52), on chondrocyte apoptosis. Bovine articular chondrocytes (BACs) were cultured under hypoxic conditions to mimic cartilage environment and then treated with Fas ligand (Fas-L) to induce apoptosis. The expression of AM and its calcitonin receptor-like receptor (CLR)/receptor activity-modifying protein (RAMP) (receptor/co-receptor) was assessed by immunostaining. We evaluated the effect of AM and AM(22-52) on Fas-L-induced chondrocyte apoptosis. FAS expression was appreciated by RT-qPCR and immunostainings. The expression of hypoxia-inducible factor 1α (HIF-1α), CLR and one co-receptor (RAMP2) was evidenced. With BACs under hypoxia, cyclic adenosine monophosphate production increased dose-dependently with AM stimulation. AM significantly decreased caspase-3 activity (mean 35% decrease; p = 0.03) as a marker of Fas-L-induced apoptosis. Articular chondrocytes treated with AM showed significantly reduced cell death, along with downregulated Fas expression and production, as compared with AM(22-52). AM decreased articular chondrocyte apoptosis by downregulating a Fas receptor. These findings may pave the way for novel therapeutic approaches in osteoarthritis.

show abstract

“…P0126; Beyotime Institute of Biotechnology). The cells were observed using a fluorescence microscope (magnification, x100), in which five fields were randomly selected, and the TUNEL and DAPI stained nuclei in the cells were counted manually (40). The percentage of positive cells was calculated using the following equation: TUNEL-positive cells (%)=(number of TUNEL positive cells/total number of cells) x 100%, as previously described (41).…”

Section: Detection Of Apoptosismentioning

confidence: 99%

Non‑cytotoxic doses of shikonin inhibit lipopolysaccharide‑induced TNF‑α expression via activation of the AMP‑activated protein kinase signaling pathway

Zhang

Gao

et al. 2020

Exp Ther Med

View full text Add to dashboard Cite

Shikonin has been reported to exhibit a wide variety of medical functions. However, the strong non-selective cytotoxicity of shikonin can restrict its clinical application. The aim of the present study was to investigate the effects of shikonin at non-cytotoxic doses on the pro-inflammation functions of monocytes and macrophages. The present results suggested that the non-cytotoxic doses of shikonin effectively inhibited lipopolysaccharide (LPS)-induced reactive oxygen species production, NF-κB activation and TNF-α expression in RAW 264.7 mouse macrophages via AMP-activated protein kinase (AMPK) signaling pathway. In addition, the non-cytotoxic doses of shikonin downregulated LPS-induced TNF-α expression via AMPK signaling activation in primary murine bone marrow-derived macrophages, and also in monocytes cultured ex vivo from patients with chronic obstructive pulmonary disease (COPD). The present in vivo results indicated that the low-toxic dose of shikonin suppressed LPS-induced endotoxin shock and TNF-α expression in mice. Collectively, the present results may provide clinical and translational relevance for treating COPD and other TNF-α-related inflammatory disorders.

show abstract

Overexpression of adrenomedullin protects mesenchymal stem cells against hypoxia and serum deprivation‑induced apoptosis via the Akt/GSK3β and Bcl‑2 signaling pathways

Cited by 20 publications

References 50 publications

Low-Frequency Magnetic Fields (LF-MFs) Inhibit Proliferation by Triggering Apoptosis and Altering Cell Cycle Distribution in Breast Cancer Cells

Low-Frequency Magnetic Fields (LF-MFs) Inhibit Proliferation by Triggering Apoptosis and Altering Cell Cycle Distribution in Breast Cancer Cells

Adrenomedullin and truncated peptide adrenomedullin(22-52) affect chondrocyte response to apoptotis in vitro: downregulation of FAS protects chondrocyte from cell death

Non‑cytotoxic doses of shikonin inhibit lipopolysaccharide‑induced TNF‑α expression via activation of the AMP‑activated protein kinase signaling pathway

Contact Info

Product

Resources

About

Overexpression of adrenomedullin protects mesenchymal stem cells against hypoxia and serum deprivation‑induced apoptosis via the Akt/GSK3β and Bcl‑2 signaling pathways

Cited by 20 publications

References 50 publications

Low-Frequency Magnetic Fields (LF-MFs) Inhibit Proliferation by Triggering Apoptosis and Altering Cell Cycle Distribution in Breast Cancer Cells

Low-Frequency Magnetic Fields (LF-MFs) Inhibit Proliferation by Triggering Apoptosis and Altering Cell Cycle Distribution in Breast Cancer Cells

Adrenomedullin and truncated peptide adrenomedullin(22-52) affect chondrocyte response to apoptotis in vitro: downregulation of FAS protects chondrocyte from cell death

Non‑cytotoxic doses of shikonin inhibit lipopolysaccharide‑induced TNF‑&alpha; expression via activation of the AMP‑activated protein kinase signaling pathway

Contact Info

Product

Resources

About

Non‑cytotoxic doses of shikonin inhibit lipopolysaccharide‑induced TNF‑α expression via activation of the AMP‑activated protein kinase signaling pathway