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Apoptosis AND MST1

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https://www.readbyqxmd.com/read/29155025/understanding-the-role-of-mammalian-sterile-20-like-kinase-1-mst1-in-cardiovascular-disorders
#1
REVIEW
Yang Yang, Haichang Wang, Zhiqiang Ma, Wei Hu, Dongdong Sun
Hippo signaling is a conserved pathway and plays important role in controlling cell proliferation and differentiation. As critical components of the Hippo pathway in mammals, mammalian sterile 20-like kinase 1 (MST1) participate in cell apoptosis and cell proliferation. Yes-associated protein (YAP) acts as a downstream transcriptional co-activator of MST1. MST1 is present in heart tissue and helps determine the fate of cardiomyocytes by regulating the balance between autophagy and apoptosis. Recent studies showed MST1 signaling is an essential participant in many cardiovascular disorders, including aortic dissection, aortic aneurysm, atherosclerosis, myocardial ischemic injury, and cardiomyopathy...
November 15, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29127009/nicorandil-alleviates-myocardial-injury-and-post-infarction-cardiac-remodeling-by-inhibiting-mst1
#2
Shanjie Wang, Yanhong Fan, Xinyu Feng, Chuang Sun, Zhaofeng Shi, Tian Li, Jianjun Lv, Zhi Yang, Zhijing Zhao, Dongdong Sun
BACKGROUND: Cardiomyocyte autophagy and apoptosis are crucial events underlying the development of cardiac abnormalities and dysfunction after myocardial infarction (MI). A better understanding of the cell signaling pathways involved in cardiac remodeling may support the development of new therapeutic strategies for the treatment of heart failure (HF) after MI. METHODS: A cardiac MI injury model was constructed by ligating the left anterior descending (LAD) coronary artery...
November 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29108216/-research-advances-in-the-role-of-the-hippo-signaling-pathway-in-pathogenesis-of-liver-cancer
#3
L Yuan, Z W Li
The Hippo signaling pathway consists of four core components in mammals, i.e., Mst1/2, WW45, Mob1, and LATS1/2, which can inhibit the transcriptional coactivator YAP from entering the nucleus, maintain the balance between cell proliferation and apoptosis, control organ size, and maintain homeostasis. If the core components of the Hippo signaling pathway are inactivated due to gene mutation or epigenetic alterations, YAP is overexpressed and activated in the nucleus, which then induces excessive cell proliferation and inhibits cell apoptosis...
October 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/29098035/mammalian-sterile-20-like-kinase-1-expression-and-its-prognostic-significance-in-patients-with-breast-cancer
#4
Xiao-Yan Lin, Feng-Feng Cai, Ming-Hong Wang, Xin Pan, Fang Wang, Lu Cai, Rong-Rong Cui, Su Chen, Ewelina Biskup
Mammalian sterile 20-like kinase 1 (Mst1) is a major inhibitor of cell proliferation, and is involved in apoptosis, oncogenesis and organ growth via its ubiquitously encoded serine threonine kinase. Previous studies have demonstrated that Mst1 has a tumor suppressor function in human breast cancer. Mst1 deletion or mutation is associated with tumorigenesis, whereas Mst1 overexpression leads to tumor cell apoptosis and decreases proliferation of tumor cells. Our previous study reported the tumor suppressive function of Mst1, and debated Mst1 as a prognostic factor in human breast cancer...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29063978/mst1-regulates-colorectal-cancer-stress-response-via-inhibiting-bnip3-related-mitophagy-by-activation-of-jnk-p53-pathway
#5
Qi Li, Feng Qi, Xiangchao Meng, Chenpei Zhu, Yingtang Gao
The Hippo-Mst1 pathway is associated with tumor development and progression. However, little evidence is available for its role in colorectal cancer (CRC) stress response via mitochondrial homeostasis. In this study, we conducted gain-of function assay about Mst1 in CRC via adenovirus transfection. Then, cellular viability and apoptosis were measured via MTT, TUNEL assay, and typan blue staining. Mitochondrial function was detected via JC1 staining, mPTP opening assay, and immunofluorescence of cyt-c. Mitophagy was observed via western blots and immunofluorescence...
October 24, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/29054447/deletion-ofmst1-attenuates-neuronal-loss-andimproves-neurological-impairment-inarat-model-oftraumatic-brain-injury
#6
Di Li, Haibo Ni, Qin Rui, Rong Gao, Gang Chen
Neuronal cell death following traumatic brain injury (TBI) is a considerable contributor to neurological deficits. In our work, we explored the functions of Mammalian STE20-like kinase-1 (Mst1), a apoptosis-promoting kinase and aslo a pivotal bridgebuilder of apoptotic signaling, in the etiopathogenesis of an experimental rat model of TBI. We found that the phosphorylation level of Mst1 in injured area was significantly increased after TBI. Furthermore, we discovered that inhibition of Mst1 phosphorylation can effectively reduce neuronal cell death by inhibiting the activation of caspase 3 and suppressing the damage of DNA during TBI...
October 17, 2017: Brain Research
https://www.readbyqxmd.com/read/28990064/gaseous-signalling-molecule-so2-via-hippo%C3%A2-mst-pathway-to-improve-myocardial-fibrosis-of-diabetic-rats
#7
Maojun Liu, Shengquan Liu, Wenting Tan, Fen Tang, Junrong Long, Zining Li, Biao Liang, Chun Chu, Jun Yang
Recent studies have indicated the existence of an endogenous sulfur dioxide (SO2)‑generating system in the cardiovascular system. The present study aimed to discuss the function and regulatory mechanism of gaseous signal molecule SO2 in inhibiting apoptosis and endoplasmic reticulum stress (ERS) via the Hippo‑MST signaling pathway to improve myocardial fibrosis of diabetic rats. A total of 40 male Sprague‑Dawley rats were randomly divided into four groups (10 rats per group): Normal control group (control group), diabetic rats group [streptozotocin (STZ) group], SO2 intervention group (STZ+SO2 group) and diabetes mellitus rats treated with L‑Aspartic acid β‑hydroxamate (HDX) group (HDX group)...
December 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28893403/energy-restriction-affect-liver-development-in-hu-sheep-ram-lambs-through-hippo-signaling-pathway
#8
Ting-Ting Zhang, Guo-Min Zhang, Yu-Hang Jin, Yi-Xuan Guo, Zhen Wang, Yi-Xuan Fan, M A El-Samahy, Feng Wang
This study aimed to evaluate the effects of dietary energy restriction on postnatal liver development in Hu sheep ram lambs. A total of 16 ram lambs were randomly divided into two groups: 100% energy requirements diet and 55% energy requirements diet, which were fed for 75 d. Results showed that the final body and liver weights decreased with energy restriction (p <0.05). Energy restriction caused a significant decrease in the levels of circulating insulin-like growth factor 1 (IGF1) and an increase in growth hormone secretion (p <0...
September 2, 2017: Tissue & Cell
https://www.readbyqxmd.com/read/28835703/neuroprotective-effects-of-cgp3466b-on-apoptosis-are-modulated-by-protein-l-isoaspartate-d-aspartate-o-methyltransferase-mst1-pathways-after-traumatic-brain-injury-in-rats
#9
Feng Liang, Ligen Shi, Jingwei Zheng, Sheng Chen, Yangxin Wang, Jianmin Zhang
Neuronal apoptosis chiefly contributes to the cell loss following traumatic brain injury (TBI). CGP3466B is a compound related to the anti-Parkinsonism drug R-(-)-deprenyl. Previous studies have illuminated anti-apoptosis effects of CGP3466B in different cell lines, but the underlying mechanisms have not been fully elucidated. Mammalian sterile 20 (STE20)-like kinase1 (Mst1) is a core component of the Hippo signaling pathway. Protein-L-isoaspartate (D-aspartate) O-methyltransferase (PCMT1) is an enzyme that repairs damaged L-isoaspartyl residues in proteins...
August 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28757479/the-functions-of-the-hippo-signaling-pathway-in-immune-cells
#10
REVIEW
Shu-juan Yu, Jing Geng, Lan-fen Chen
The Hippo signaling pathway, first identified in Drosophila, has emerged as a critical regulator for controlling the size of organs. Activation of the Hippo signaling pathway negatively regulates the Yorkie ortholog YAP in multiple organs, important in the regulation of cell proliferation, differentiation, and apoptosis during development. The Serine/Threonine protein kinases MST1 and MST2, mammalian homologs of the Drosophila Hippo kinase, play central roles in the Hippo signaling pathway in mammals. Recent studies reveal that non-canonical Hippo signaling pathways are also involved in the regulation of various other biological processes, particularly the important roles of MST1 and MST2 kinases in immune cell activation, adhesion, migration, growth, and apoptosis...
July 20, 2017: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/28552397/morin-attenuates-diethylnitrosamine-induced-rat-liver-fibrosis-and-hepatic-stellate-cell-activation-by-co-ordinated-regulation-of-hippo-yap-and-tgf-%C3%AE-1-smad-signaling
#11
NaveenKumar Perumal, MadanKumar Perumal, Devaraj Halagowder, NiranjaliDevaraj Sivasithamparam
Despite great progress in understanding the activation of hepatic stellate cells (HSCs) during liver fibrosis, therapeutic approaches to inhibit HSC activation remain very limited. Recent reports highlight Yes-associated protein (Yap) and transforming growth factor-β1 (TGF-β1) as critical regulators of HSC activation and henceforth a compound targeting Hippo/Yap and TGF-β1/Smad pathways would be a potential anti-fibrotic candidate. Morin, a dietary flavonoid, was earlier reported to inhibit HSC proliferation and induction of apoptosis of cultured HSCs, mainly by suppressing Wnt/β-catenin and NF-κB signaling, but its effect on Hippo/Yap and TGF-β1/Smad pathways was not determined...
September 2017: Biochimie
https://www.readbyqxmd.com/read/28534197/pcmt1-ameliorates-neuronal-apoptosis-by-inhibiting-the-activation-of-mst1-after-subarachnoid-hemorrhage-in-rats
#12
Ligen Shi, Ammar Al-Baadani, Keren Zhou, Anwen Shao, Shenbin Xu, Sheng Chen, Jianmin Zhang
Mammalian sterile 20-like kinase 1 (MST1) is found to promote neuronal apoptosis. Protein-L-isoaspartate (D-aspartate) O-methyltransferase (PCMT1), an anti-apoptosis factor, was recently identified as an MST1-interacting protein. This study aims to explore the potential role of PCMT1 in reducing MST1-induced neuronal apoptosis after subarachnoid hemorrhage (SAH) in rats. One hundred ninety-eight male Sprague-Dawley rats were used. An exogenous PCMT1 agonist, CGP 3466B, was injected subcutaneously 1 h after the SAH induced by endovascular perforation...
May 22, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/28487119/the-mammalian-ste20-like-kinase-1-mst1-is-a-substrate-for-the-apoptosis-inhibiting-protein-kinase-ck2
#13
Christina Servas, Sandra Kiehlmeier, Julia Hach, Rebecca Gross, Claudia Götz, Mathias Montenarh
Apoptosis and the response to cell stress are evolutionary highly conserved mechanisms. Both processes require strict regulation, which is often performed by protein kinases. The mammalian Sterile 20-like kinase 1 (MST1) is a pro-apoptotic protein kinase, which is activated and cleaved by caspases upon the induction of cell stress. Being a phosphoprotein itself, the activity of MST1 is regulated by phosphorylation. Protein kinase CK2 is an anti-apoptotic protein kinase which seems to be involved in the regulation of many different cellular processes including apoptosis...
May 6, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28480597/melatonin-protects-against-diabetic-cardiomyopathy-through-mst1-sirt3-signaling
#14
Mingming Zhang, Jie Lin, Shanjie Wang, Zheng Cheng, Jianqiang Hu, Tingting Wang, Wanrong Man, Tao Yin, Wenyi Guo, Erhe Gao, Russel J Reiter, Haichang Wang, Dongdong Sun
This study investigated the effects of melatonin on diabetic cardiomyopathy (DCM) and determined the underlying mechanisms. Echocardiography indicated that melatonin notably mitigated the adverse left ventricle remodeling and alleviated cardiac dysfunction in DCM. The mechanisms were attributed to increased autophagy, reduced apoptosis, and alleviated mitochondrial dysfunction. Furthermore, melatonin inhibited Mst1 phosphorylation and promoted Sirt3 expression in DCM. These results indicated that melatonin may exert its effects through Mst1/Sirt3 signaling...
May 8, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28469576/plant-produced-asialo-erythropoietin-restores-pancreatic-beta-cell-function-by-suppressing-mammalian-sterile-20-like-kinase-mst1-and-caspase-3-activation
#15
Elena Arthur, Farooqahmed S Kittur, Yuan Lin, Chiu-Yueh Hung, David C Sane, Jiahua Xie
Pancreatic beta-cell death adversely contributes to the progression of both type I and II diabetes by undermining beta-cell mass and subsequently diminishing endogenous insulin production. Therapeutics to impede or even reverse the apoptosis and dysfunction of beta-cells are urgently needed. Asialo-rhuEPO, an enzymatically desialylated form of recombinant human erythropoietin (rhuEPO), has been shown to have cardioprotective and neuroprotective functions but with no adverse effects like that of sialylated rhuEPO...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28454447/inhibitory-effect-and-mechanism-of-exogenous-mammalian-sterile-20-like-kinase-1-on-the-growth-of-human-colorectal-cancer
#16
Jian Wu, Xiaohong Yang, Hongfei Lu, Liqiao Liu, Baohua Xu, Shuangyan Zheng, Bo Yu, Kemin Jie, Fusheng Wan
The present study aimed to observe the inhibitory effect and preliminary mechanism of exogenous mammalian sterile 20-like kinase 1 (MST1) on the growth of colorectal cancer SW480 cells. The SW480 cells were randomly divided into the following groups: Control, empty enhanced green fluorescent protein (EGFP) plasmid (pEGFP-N1), MST1 EGFP plasmid (pEGFP-MST1), 20 µmol/l fluorouracil (5-FU) and pEGFP-MST1 + 5-FU. An MTS colorimetric assay was used to detect cell viability, Hoechst 33342 staining was used to observe cell apoptosis, and western blotting and immunohistochemistry were used to detect the levels of the proteins MST1, yes-associated protein (YAP), phospho-YAP1 (Ser127), p53 and p53 upregulated modulator of apoptosis (PUMA)...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28448802/ddk-promotes-tumor-chemoresistance-and-survival-via-multiple-pathways
#17
Nanda Kumar Sasi, Arjun Bhutkar, Nathan J Lanning, Jeffrey P MacKeigan, Michael Weinreich
DBF4-dependent kinase (DDK) is a two-subunit kinase required for initiating DNA replication at individual origins and is composed of CDC7 kinase and its regulatory subunit DBF4. Both subunits are highly expressed in many diverse tumor cell lines and primary tumors, and this is correlated with poor prognosis. Inhibiting DDK causes apoptosis of tumor cells, but not normal cells, through a largely unknown mechanism. Firstly, to understand why DDK is often overexpressed in tumors, we identified gene expression signatures that correlate with DDK high- and DDK low-expressing lung adenocarcinomas...
May 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28366538/morin-impedes-yap-nuclear-translocation-and-fosters-apoptosis-through-suppression-of-wnt-%C3%AE-catenin-and-nf-%C3%AE%C2%BAb-signaling-in-mst1-overexpressed-hepg2-cells
#18
NaveenKumar Perumal, MadanKumar Perumal, Anbarasu Kannan, Kumar Subramani, Devaraj Halagowder, NiranjaliDevaraj Sivasithamparam
Recent clinical and experimental evidences strongly acclaim Yes-associated protein (Yap), a key oncogenic driver in liver carcinogenesis, as a therapeutic target. Of the known multiple schemes to inhibit Yap activity, activation of Mammalian Sterile 20-like Kinase 1 (Mst1), an upstream regulator of Yap, appears to be a promising one. In this study, we hypothesize that morin, a bioflavonoid, mediates its anti-cancer effect through the activation of Mst1/hippo signaling in liver cancer cells. To test this hypothesis, both full length Mst1 (F-Mst1) and kinase active N-terminal Mst1 (N-Mst1)-overexpressed HepG2 cells were used...
June 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28210902/deletion-of-mammalian-sterile-20-like-kinase-1-attenuates-neuronal-loss-and-improves-locomotor-function-in-a-mouse-model-of-spinal-cord-trauma
#19
Pan-Feng Wang, Da-Yuan Xu, Yuntong Zhang, Xiao-Bin Liu, Yan Xia, Pan-Yu Zhou, Qing-Ge Fu, Shuo-Gui Xu
Neuronal cell death following spinal cord injury (SCI) is an important contributor to neurological deficits. The purpose of our work was to delineate the function of mammalian sterile 20-like kinase 1 (Mst1), a pro-apoptotic kinase and key mediator of apoptotic signaling, in the pathogenesis of an experimental mouse model of SCI. Male mice received a mid-thoracic spinal contusion injury, and it was found that phosphorylation of Mst1 at the injured site was enhanced significantly following SCI. Furthermore, when compared to the wild-type controls, Mst1-deficient mice displayed improved locomotor function by increased Basso mouse scale score...
July 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28150487/structural-insights-into-the-regulation-of-hippo-signaling
#20
REVIEW
Leah Cairns, Thao Tran, Jennifer M Kavran
During development, the Hippo pathway regulates the balance between cell proliferation and apoptosis to control organ size. Appropriate Hippo signaling is associated with stem cell maintenance, while inappropriate signaling can result in tumorigenesis and cancer. Cellular and genetic investigations have identified core components and determined that complex formation and protein phosphorylation are crucial regulatory events. The recent spate of high-resolution structures of Hippo pathway components have begun to reveal the molecular mechanisms controlling these events, including the molecular determinates of complex formation between YAP and TEAD, the role of phosphorylation in controlling complex formation by Mob, and the conformational changes accompanying Mst1/2 kinase domain activation...
March 17, 2017: ACS Chemical Biology
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