Protein-Serine-Threonine Kinases

Publication Title: 
Hepatology (Baltimore, Md.)

RNA-binding proteins (RBPs) play a major role in the control of messenger RNA (mRNA) turnover and translation rates. We examined the role of the RBP, human antigen R (HuR), during cholestatic liver injury and hepatic stellate cell (HSC) activation. HuR silencing attenuated fibrosis development in vivo after BDL, reducing liver damage, oxidative stress, inflammation, and collagen and alpha smooth muscle actin (α-SMA) expression. HuR expression increased in activated HSCs from bile duct ligation mice and during HSC activation in vitro, and HuR silencing markedly reduced HSC activation.

Author(s): 
Woodhoo, Ashwin
Iruarrizaga-Lejarreta, Marta
Beraza, Naiara
García-Rodríguez, Juan L.
Embade, Nieves
Fernández-Ramos, David
Martínez-López, Nuria
Gutierrez-de Juan, Virginia
Arteta, Beatriz
Caballeria, Juan
Lu, Shelly C.
Mato, José M.
Varela-Rey, Marta
Martínez-Chantar, María L.
Publication Title: 
Gastroenterology

BACKGROUND & AIMS: Patients with cirrhosis are at high risk for developing hepatocellular carcinoma (HCC), and their liver tissues have abnormal levels of S-adenosylmethionine (SAMe). Glycine N-methyltransferase (GNMT) catabolizes SAMe, but its expression is down-regulated in HCC cells. Mice that lack GNMT develop fibrosis and hepatomas and have alterations in signaling pathways involved in carcinogenesis. We investigated the role of GNMT in human HCC cell lines and in liver carcinogenesis in mice.

Author(s): 
Martínez-López, Nuria
García-Rodríguez, Juan L.
Varela-Rey, Marta
Gutiérrez, Virginia
Fernández-Ramos, David
Beraza, Naiara
Aransay, Ana M.
Schlangen, Karin
Lozano, Juan Jose
Aspichueta, Patricia
Luka, Zigmund
Wagner, Conrad
Evert, Matthias
Calvisi, Diego F.
Lu, Shelly C.
Mato, José M.
Martínez-Chantar, María L.
Publication Title: 
Nutrition Research (New York, N.Y.)

We have previously shown that green and black tea extracts increase the phosphorylation of AMP-activated protein kinase (AMPK) and HMG-CoA reductase in rat hepatoma cells in culture, concomitant with a decrease in cholesterol synthesis. In the present study, we evaluated the ability of a single oral dose of green or black tea extract to promote the phosphorylation of AMPK, liver kinase B1 (LKB1, an AMPK-kinase), and HMG-CoA reductase in mouse liver.

Author(s): 
Banerjee, Subhashis
Ghoshal, Sarbani
Porter, Todd D.
Publication Title: 
PloS One

Acute Respiratory Distress Syndrome (ARDS) is a clinical syndrome characterized by diffuse alveolar damage usually secondary to an intense host inflammatory response of the lung to a pulmonary or extrapulmonary infectious or non-infectious insult often leading to the development of intra-alveolar and interstitial fibrosis. Curcumin, the principal curcumoid of the popular Indian spice turmeric, has been demonstrated as an anti-oxidant and anti-inflammatory agent in a broad spectrum of diseases.

Author(s): 
Avasarala, Sreedevi
Zhang, Fangfang
Liu, Guangliang
Wang, Ruixue
London, Steven D.
London, Lucille
Publication Title: 
Journal of Parkinson's Disease

Oxidative stress plays an important role in the degeneration of dopaminergic neurons in Parkinson's disease (PD). Disruptions in the physiologic maintenance of the redox potential in neurons interfere with several biological processes, ultimately leading to cell death. Evidence has been developed for oxidative and nitrative damage to key cellular components in the PD substantia nigra.

Author(s): 
Dias, Vera
Junn, Eunsung
Mouradian, M. Maral
Publication Title: 
The Journal of Pharmacology and Experimental Therapeutics

Tumor-induced angiogenesis is essential for invasive growth and hematogenous metastasis of adenoid cystic carcinoma (ACC), a highly aggressive neoplasm mostly occurring in salivary glands. Previous studies have indicated that strategies directed against angiogenesis will help develop new therapeutic agents for ACC. The Chinese folk medicine licorice has been used for years as a natural remedy for angiogenesis-related diseases.

Author(s): 
Sun, Zhi-Jun
Chen, Gang
Zhang, Wei
Hu, Xiang
Huang, Cong-Fa
Wang, Yu-Fan
Jia, Jun
Zhao, Yi-Fang
Publication Title: 
Cell Cycle (Georgetown, Tex.)

In this study, we report the functional characterization of a new ent-kaurene diterpenoid termed pharicin A, which was originally isolated from Isodon, a perennial shrub frequently used in Chinese folk medicine for tumor treatment. Pharicin A induces mitotic arrest in leukemia and solid tumor-derived cells identified by their morphology, DNA content and mitotic marker analyses. Pharicin A-induced mitotic arrest is associated with unaligned chromosomes, aberrant BubR1 localization and deregulated spindle checkpoint activation.

Author(s): 
Xu, Han-Zhang
Huang, Ying
Wu, Ying-Li
Zhao, Yong
Xiao, Wei-Lie
Lin, Qi-Shan
Sun, Han-Dong
Dai, Wei
Chen, Guo-Qiang
Publication Title: 
Circulation Journal: Official Journal of the Japanese Circulation Society

BACKGROUND: Common variations in the gene with no-lysine kinase 1 (WNK1) are associated with hypertension, but because of gene-environment interaction, it is difficult to fully identify the genetic contribution of WNK1 gene polymorphism to blood pressure (BP) variability. The aim of this study was to identify the effect of common WNK1 variants on the shift of BP during strict dietary interventions of salt or potassium intake.

Author(s): 
Liu, Fuqiang
Zheng, Shuhui
Mu, Jianjun
Chu, Chao
Wang, Lan
Wang, Yang
Xiao, Hongyu
Wang, Dan
Cao, Yu
Ren, Keyu
Liu, Enqi
Yuan, Zuyi
Publication Title: 
FASEB journal: official publication of the Federation of American Societies for Experimental Biology

Oxidative stress is believed to be an important factor in the development of age-related diseases, and studies in lower organisms have established links between oxidative stress tolerance and longevity. We have hypothesized that aging is associated with a reduced ability to mount acute host defenses to oxidant injury, which increases the vulnerability of aged cells to stress. We tested this hypothesis by using primary hepatocytes from young (4-6 months) and aged (24-26 months) rats. Old hepatocytes were more sensitive to H2O2-induced apoptosis than were young cells.

Author(s): 
Ikeyama, Shizuo
Kokkonen, Gertrude
Shack, Sonsoles
Wang, Xian-Tao
Holbrook, Nikki J.
Publication Title: 
The Journal of Biological Chemistry

Akt is a serine-threonine kinase that mediates a variety of cellular responses to external stimuli. During postnatal development, Akt signaling in the heart was up-regulated when the heart was rapidly growing and was down-regulated by caloric restriction, suggesting a role of Akt in nutrient-dependent regulation of cardiac growth. Consistent with this notion, reductions in Akt, 70-kDa S6 kinase 1, and eukaryotic initiation factor 4E-binding protein 1 phosphorylation were observed in mice with cardiac-specific deletion of insulin receptor gene, which exhibit a small heart phenotype.

Author(s): 
Shiojima, Ichiro
Yefremashvili, Mikkael
Luo, Zhengyu
Kureishi, Yasuko
Takahashi, Akihiro
Tao, Jingzang
Rosenzweig, Anthony
Kahn, C. Ronald
Abel, E. Dale
Walsh, Kenneth

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