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MHY1485

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https://www.readbyqxmd.com/read/29039446/protective-effect-of-autophagy-in-neural-ischemia-and-hypoxia-negative-regulation-of-the-wnt-%C3%AE-catenin-pathway
#1
Zhen-Yu Shi, Jie-Xin Deng, Su Fu, Lai Wang, Qiang Wang, Bin Liu, Yong-Qiang Li, Jin-Bo Deng
Autophagy is a highly conserved process of self-digestion to promote cell survival in response to nutrient starvation and other metabolic stresses. However, whether ischemic-hypoxic (IH) injury-induced autophagy acts as a neuroprotective mechanism or leads to neuroinjury is a subject of debate. It is known that autophagy is regulated by signaling pathways, including the mammalian target of rapamycin pathway. However, in neural IH injury, whether other signaling pathways are involved in the regulation of autophagy remains to be fully elucidated...
September 28, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28935818/increased-mir-124-3p-in-microglial-exosomes-following-traumatic-brain-injury-inhibits-neuronal-inflammation-and-contributes-to-neurite-outgrowth-via-their-transfer-into-neurons
#2
Shan Huang, Xintong Ge, Jinwen Yu, Zhaoli Han, Zhenyu Yin, Ying Li, Fanglian Chen, Haichen Wang, Jianning Zhang, Ping Lei
Neuronal inflammation is the characteristic pathologic change of acute neurologic impairment and chronic traumatic encephalopathy after traumatic brain injury (TBI). Inhibiting the excessive inflammatory response is essential for improving the neurologic outcome. To clarify the regulatory mechanism of microglial exosomes on neuronal inflammation in TBI, we focused on studying the impact of microglial exosomal miRNAs on injured neurons in this research. We used a repetitive (r)TBI mouse model and harvested the injured brain extracts from the acute to the chronic phase of TBI to treat cultured BV2 microglia in vitro The microglial exosomes were collected for miRNA microarray analysis, which showed that the expression level of miR-124-3p increased most apparently in the miRNAs...
September 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28817115/administration-of-follicle-stimulating-hormone-induces-autophagy-via-upregulation-of-hif-1%C3%AE-in-mouse-granulosa-cells
#3
Jilong Zhou, Wang Yao, Chengyu Li, Wangjun Wu, Qifa Li, Honglin Liu
Recent studies reported the important role of autophagy in follicular development. However, the underlying molecular mechanisms remain elusive. In this study, we investigated the effect of follicle-stimulating hormone (FSH) on mouse granulosa cells (MGCs). Results indicated that autophagy was induced by FSH, which is known to be the dominant hormone regulating follicular development and granulosa cell (GC) proliferation. The activation of mammalian target of rapamycin (mTOR), a master regulator of autophagy, was inhibited during the process of MGC autophagy...
August 17, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28700632/inflammation-dependent-mtorc1-signaling-interferes-with-the-switch-from-keratinocyte-proliferation-to-differentiation
#4
Claudia Buerger, Nitesh Shirsath, Victoria Lang, Alina Berard, Sandra Diehl, Roland Kaufmann, Wolf-Henning Boehncke, Peter Wolf
Psoriasis is a frequent and often severe inflammatory skin disease, characterized by altered epidermal homeostasis. Since we found previously that Akt/mTOR signaling is hyperactivated in psoriatic skin, we aimed at elucidating the role of aberrant mTORC1 signaling in this disease. We found that under healthy conditions mTOR signaling was shut off when keratinocytes switch from proliferation to terminal differentiation. Inflammatory cytokines (IL-1β, IL-17A, TNF-α) induced aberrant mTOR activity which led to enhanced proliferation and reduced expression of differentiation markers...
2017: PloS One
https://www.readbyqxmd.com/read/28694352/protease-activated-receptor-2-promotes-kidney-tubular-epithelial-inflammation-by-inhibiting-autophagy-via-the-pi3k-akt-mtor-signalling-pathway
#5
Chunyang Du, Tao Zhang, Xia Xiao, Yonghong Shi, Huijun Duan, Yunzhuo Ren
Protease-activated receptor-2 (PAR2), which belongs to a specific class of the G-protein-coupled receptors, is central to several inflammation processes. However, the precise molecular mechanism involved remains undefined. Autophagy has been previously shown to affect inflammation. In the present study, we examine the effect of PAR2 on kidney tubular epithelial autophagy and on autophagy-related inflammation and reveal the underlying mechanism involved. Autophagic activity and levels of autophagic marker LC3 were examined in human kidney tubular epithelial cells with PAR2 knockdown or overexpression...
August 2, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28624790/co-targeting-of-igf1r-mtor-pathway-by-mir-497-and-mir-99a-impairs-hepatocellular-carcinoma-development
#6
Henghui Cheng, Jin Xue, Shouhua Yang, Yaobin Chen, Yu Wang, Yuanli Zhu, Xiaoyan Wang, Dong Kuang, Qiurong Ruan, Yaqi Duan, Guoping Wang
Persistent activation of IGF1R/mTOR signaling pathway plays crucial role in the development of hepatocellular carcinoma (HCC). Therefore, our goal was to elucidate microRNAs (miRNAs) targeting IGF1R/mTOR and the therapeutic potential of single or dual miRNA on HCC development. In this study, we found that miR-497 and miR-99a that target the 3'-UTR of both IGF1R and mTOR were down-regulated in HCC human tissues and cell lines. Functional assay revealed that ectopic expression of miR-497 or miR-99a in HCC cells resulted in a significant inhibition on tumor growth and invasiveness in vitro and tumor development in vivo via repressing the expression of IGF1R and mTOR...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28575052/myogenic-differentiation-of-vcp-disease-induced-pluripotent-stem-cells-a-novel-platform-for-drug-discovery
#7
Katrina J Llewellyn, Angèle Nalbandian, Lan N Weiss, Isabela Chang, Howard Yu, Bibo Khatib, Baichang Tan, Vanessa Scarfone, Virginia E Kimonis
Valosin Containing Protein (VCP) disease is an autosomal dominant multisystem proteinopathy caused by mutations in the VCP gene, and is primarily associated with progressive muscle weakness, including atrophy of the pelvic and shoulder girdle muscles. Currently, no treatments are available and cardiac and respiratory failures can lead to mortality at an early age. VCP is an AAA ATPase multifunction complex protein and mutations in the VCP gene resulting in disrupted autophagic clearance. Due to the rarity of the disease, the myopathic nature of the disorder, ethical and practical considerations, VCP disease muscle biopsies are difficult to obtain...
2017: PloS One
https://www.readbyqxmd.com/read/28243129/polydatin-regulates-proliferation-apoptosis-and-autophagy-in-multiple-myeloma-cells-through-mtor-p70s6k-pathway
#8
Baojun Yang, Shunxin Zhao
BACKGROUND: Polydatin (PD) plays an important role in suppressing platelet aggregation, reducing blood lipid, restoring microcirculation and protecting from myocardial ischemia/reperfusion injury and shock. In addition, PD possesses anticancer activity. However, the effect and the mechanism of PD in regulating multiple myeloma (MM) cell survival and death are still unknown. METHODS: Cell proliferation and apoptosis of RPMI 8226 cells, respectively, were analyzed by cell counting kit8 (CCK-8) assay and flow cytometry...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28103582/ampk-autophagy-inhibition-sensitizes-icaritin-induced-anti-colorectal-cancer-cell-activity
#9
Chunxian Zhou, Jun Gu, Gang Zhang, Da Dong, Qunying Yang, Min-Bin Chen, Dongfeng Xu
The current research studied the potential effect of autophagy on icaritin-induced anti-colorectal cancer (CRC) cell activity. Treatment of icaritin in both primary and established (HT-29) CRC cells induced feedback activation of autophagy, evidenced by p62 degradation, Beclin-1 and autophagy-related gene-5 (ATG-5) upregulation, as well as light chain 3B (LC3B)-GFP puncta formation. Pharmacological inhibiting of autophagy dramatically potentiated icaritin-induced CRC cell death and apoptosis. Meanwhile, shRNA-mediated knockdown of Beclin-1 or ATG-5 also sensitized icaritin-induced CRC cell death and apoptosis...
February 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28061443/mhy1485-ameliorates-uv-induced-skin-cell-damages-via-activating-mtor-nrf2-signaling
#10
Bo Yang, Qiu-Yun Xu, Chun-Yan Guo, Jin-Wen Huang, Shu-Mei Wang, Yong-Mei Li, Ying Tu, Li He, Zhi-Gang Bi, Chao Ji, Bo Cheng
Ultra Violet (UV)-caused skin cell damage is a main cause of skin cancer. Here, we studied the activity of MHY1485, a mTOR activator, in UV-treated skin cells. In primary human skin keratinocytes, HaCaT keratinocytes and human skin fibroblasts, MHY1485 ameliorated UV-induced cell death and apoptosis. mTOR activation is required for MHY1485-induced above cytoprotective actions. mTOR kinase inhibitors (OSI-027, AZD-8055 and AZD-2014) or mTOR shRNA knockdown almost abolished MHY1485-induced cytoprotection. Further, MHY1485 treatment in skin cells activated mTOR downstream NF-E2-related factor 2 (Nrf2) signaling, causing Nrf2 Ser-40 phosphorylation, stabilization/upregulation and nuclear translocation, as well as mRNA expression of Nrf2-dictated genes...
February 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/27884298/mhy1485-activates-mtor-and-protects-osteoblasts-from-dexamethasone
#11
Sai Zhao, Caiyun Chen, Shouguo Wang, Feng Ji, Yue Xie
Dexamethasone (Dex) exerts cytotoxic effects to cultured osteoblasts. The potential effect of MHY1485, a small-molecular mammalian target of rapamycin (mTOR) activator, against the process was studied here. In both osteoblastic MC3T3-E1 cells and primary murine osteoblasts, treatment with MHY1485 significantly ameliorated Dex-induced cell death and apoptosis. mTOR inhibition, through mTOR kinase inhibitor OSI-027 or mTOR shRNAs, abolished MHY1485-mediated osteoblast cytoprotection against Dex. Intriguingly, activation of mTOR complex (mTORC1), but not mTORC2, is required for MHY1485's anti-Dex activity...
December 9, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27600753/liraglutide-attenuates-the-osteoblastic-differentiation-of-mc3t3%C3%A2-e1-cells-by-modulating-ampk-mtor-signaling
#12
Xiong-Ke Hu, Xin-Hua Yin, Hong-Qi Zhang, Chao-Feng Guo, Ming-Xing Tang
Liraglutide, a synthetic analogue of glucagon-like peptide‑1, is utilized in the treatment of type 2 diabetes and obesity. Liraglutide has been previously demonstrated to prevent osteoblastic differentiation of human vascular smooth muscle cells, resulting in the slowing of arterial calcification, however, its effect on bone formation remains unclear. The present study investigated the effect of liraglutide on osteoblastic differentiation using Alizarin Red S staining, and examined the molecular mechanisms underlying the regulatory effect by western blot analysis...
October 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/26081285/-pro-renin-receptor-regulates-autophagy-and-apoptosis-in-podocytes-exposed-to-high-glucose
#13
Caixia Li, Helmy M Siragy
High glucose reduces autophagy and enhances apoptosis of podocytes. Previously, we reported that high glucose induced podocyte injury through upregulation of the (pro)renin receptor (PRR). We hypothesized that increasing PRR reduces autophagy and increases apoptosis of mouse podocytes exposed to high glucose via activation of the PI3K/Akt/mTOR signaling pathway. Mouse podocytes were cultured in normal (5 mmol/l) or high (25 mmol/l) d-glucose for 48 h. High glucose significantly increased mRNA and protein levels of PRR, phosphorylation of PI3K/Akt/mTOR, and p62...
August 1, 2015: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/25710488/promotion-of-ovarian-follicle-growth-following-mtor-activation-synergistic-effects-of-akt-stimulators
#14
Yuan Cheng, Jaehong Kim, Xiao Xiao Li, Aaron J Hsueh
Mammalian target of rapamycin (mTOR) is a serine/threonine kinase and mTOR signaling is important in regulating cell growth and proliferation. Recent studies using oocyte- and granulosa cell-specific deletion of mTOR inhibitor genes TSC1 or TSC2 demonstrated the important role of mTOR signaling in the promotion of ovarian follicle development. We now report that treatment of ovaries from juvenile mice with an mTOR activator MHY1485 stimulated mTOR, S6K1 and rpS6 phosphorylation. Culturing ovaries for 4 days with MHY1485 increased ovarian explant weights and follicle development...
2015: PloS One
https://www.readbyqxmd.com/read/22927967/inhibitory-effect-of-mtor-activator-mhy1485-on-autophagy-suppression-of-lysosomal-fusion
#15
Yeon Ja Choi, Yun Jung Park, Ji Young Park, Hyoung Oh Jeong, Dae Hyun Kim, Young Mi Ha, Ji Min Kim, Yu Min Song, Hyoung-Sam Heo, Byung Pal Yu, Pusoon Chun, Hyung Ryong Moon, Hae Young Chung
Autophagy is a major degradative process responsible for the disposal of cytoplasmic proteins and dysfunctional organelles via the lysosomal pathway. During the autophagic process, cells form double-membraned vesicles called autophagosomes that sequester disposable materials in the cytoplasm and finally fuse with lysosomes. In the present study, we investigated the inhibition of autophagy by a synthesized compound, MHY1485, in a culture system by using Ac2F rat hepatocytes. Autophagic flux was measured to evaluate the autophagic activity...
2012: PloS One
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