Protein-Serine-Threonine Kinases

Publication Title: 
Anticancer Research

BACKGROUND: Previous studies indicate that specific extracts and the pure triterpene glycoside actein obtained from black cohosh inhibit growth of human breast cancer cells. Our aim is to identify alterations in gene expression induced by treatment with a methanolic extract (MeOH) of black cohosh. MATERIALS AND METHODS: We treated MDA-MB-453 human breast cancer cells with the MeOH extract at 40 microg/ml and collected RNA at 6 and 24 h; we confirmed the microarray results with real-time RT-PCR for 18 genes.

Author(s): 
Einbond, Linda Saxe
Su, Tao
Wu, Hsan-au
Friedman, Richard
Wang, Xiaomei
Jiang, Bei
Hagan, Timothy
Kennelly, Edward J.
Kronenberg, Fredi
Weinstein, I. Bernard
Publication Title: 
American Journal of Physiology. Endocrinology and Metabolism

Berberine, a botanical alkaloid used to control blood glucose in type 2 diabetes in China, has recently been reported to activate AMPK. However, it is not clear how AMPK is activated by berberine. In this study, activity and action mechanism of berberine were investigated in vivo and in vitro. In dietary obese rats, berberine increased insulin sensitivity after 5-wk administration. Fasting insulin and HOMA-IR were decreased by 46 and 48%, respectively, in the rats.

Author(s): 
Yin, Jun
Gao, Zhanguo
Liu, Dong
Liu, Zhijun
Ye, Jianping
Publication Title: 
Hepatology (Baltimore, Md.)

S-adenosylmethionine (SAMe) is involved in numerous complex hepatic processes such as hepatocyte proliferation, death, inflammatory responses, and antioxidant defense. One of the most relevant actions of SAMe is the inhibition of hepatocyte proliferation during liver regeneration. In hepatocytes, SAMe regulates the levels of cytoplasmic HuR, an RNA-binding protein that increases the half-life of target messenger RNAs such as cyclin D1 and A2 via inhibition of hepatocyte growth factor (HGF)-mediated adenosine monophosphate-activated protein kinase (AMPK) phosphorylation.

Author(s): 
Vázquez-Chantada, Mercedes
Ariz, Usue
Varela-Rey, Marta
Embade, Nieves
Martínez-López, Nuria
Fernández-Ramos, David
Gomez-Santos, Laura
Lamas, Santiago
Lu, Shelly C.
Martínez-Chantar, M. Luz
Mato, José M.
Publication Title: 
Hepatology (Baltimore, Md.)

Hepatic S-adenosylmethionine (SAMe) is maintained constant by the action of methionine adenosyltransferase I/III (MATI/III), which converts methionine into SAMe and glycine N-methyltransferase (GNMT), which eliminates excess SAMe to avoid aberrant methylation reactions. During liver regeneration after partial hepatectomy (PH) MATI/III activity is inhibited leading to a decrease in SAMe. This injury-related reduction in SAMe promotes hepatocyte proliferation because SAMe inhibits hepatocyte DNA synthesis.

Author(s): 
Varela-Rey, Marta
Fernández-Ramos, David
Martínez-López, Nuria
Embade, Nieves
Gomez-Santos, Laura
Beraza, Naiara
Vázquez-Chantada, Mercedes
Rodríguez, Juan
Luka, Zigmund
Wagner, Conrad
Lu, Shelly C.
Martínez-Chantar, M. Luz
Mato, José M.
Publication Title: 
Discovery Medicine

Systemic lupus erythematosus (SLE) is a common autoimmune disease with unclear etiology. Treatments for it often provide inadequate control of disease activity or are limited by side effects. Recent studies have shown that rapamycin can be an effective treatment in both murine lupus models and human SLE. We demonstrated that rapamycin could directly alter molecular abnormalities in SLE T cells related to calcium signaling but not mitochondrial function.

Author(s): 
Fernandez, David
Perl, Andras
Publication Title: 
Hepatology (Baltimore, Md.)

LKB1, originally considered a tumor suppressor, plays an important role in hepatocyte proliferation and liver regeneration. Mice lacking the methionine adenosyltransferase (MAT) gene MAT1A exhibit a chronic reduction in hepatic S-adenosylmethionine (SAMe) levels, basal activation of LKB1, and spontaneous development of nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). These results are relevant for human health because patients with liver cirrhosis, who are at risk to develop HCC, have a marked reduction in hepatic MAT1A expression and SAMe synthesis.

Author(s): 
Martínez-López, Nuria
Varela-Rey, Marta
Fernández-Ramos, David
Woodhoo, Ashwin
Vázquez-Chantada, Mercedes
Embade, Nieves
Espinosa-Hevia, Luis
Bustamante, Francisco Javier
Parada, Luis A.
Rodríguez, Manuel S.
Lu, Shelly C.
Mato, José M.
Martínez-Chantar, María L.
Publication Title: 
American Journal of Clinical Pathology

Epidemiologic studies link vitamin D deficiency to onset of type 1 diabetes mellitus (T1DM). T1DM exhibits increased inflammation, which is pronounced with microvascular complications (T1DM-MV). However, there are a paucity of data on vitamin D in T1DM-MV in relation to biomarkers of inflammation, and this formed the aim of the study. Healthy control subjects (n = 36), patients with T1DM (n = 24), and patients with T1DM-MV (n =26) were recruited. Serum vitamin D levels, monocyte toll-like receptor (TLR) 2 and TLR4 expression and nuclear factor-κB (NFκB) activity were assessed.

Author(s): 
Devaraj, Sridevi
Yun, Jung-Mi
Duncan-Staley, Catherine R.
Jialal, Ishwarlal
Publication Title: 
Lipids

Policosanol, a well-defined mixture of very long chain primary alcohols that is available as a nutraceutical product, has been reported to lower blood cholesterol levels. The present studies demonstrate that policosanol promotes the phosphorylation of AMP-kinase and HMG-CoA reductase in hepatoma cells and in mouse liver after intragastric administration, providing a possible means by which policosanol might lower blood cholesterol levels.

Author(s): 
Banerjee, Subhashis
Ghoshal, Sarbani
Porter, Todd D.
Publication Title: 
Journal of Nanobiotechnology

BACKGROUND: The development of effective drug delivery systems capable of transporting small interfering RNA (siRNA) has been elusive. We have previously reported that colorectal cancer tumor xenograft growth was arrested following treatment with liposomal preparation of siDCAMKL-1. In this report, we have utilized Nanoparticle (NP) technology to deliver DCAMKL-1 specific siRNA to knockdown potential key cancer regulators. In this study, mRNA/miRNA were analyzed using real-time RT-PCR and protein by western blot/immunohistochemistry.

Author(s): 
Sureban, Sripathi M.
May, Randal
Mondalek, Fadee G.
Qu, Dongfeng
Ponnurangam, Sivapriya
Pantazis, Panayotis
Anant, Shrikant
Ramanujam, Rama P.
Houchen, Courtney W.
Publication Title: 
Blood

Targeting cancer stem cells is of paramount importance in successfully preventing cancer relapse. Recently, in silico screening of public gene-expression datasets identified cyclooxygenase-derived cyclopentenone prostaglandins (CyPGs) as likely agents to target malignant stem cells. We show here that Δ(12)-PGJ(3), a novel and naturally produced CyPG from the dietary fish-oil ω-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA; 20:5) alleviates the development of leukemia in 2 well-studied murine models of leukemia.

Author(s): 
Hegde, Shailaja
Kaushal, Naveen
Ravindra, Kodihalli C.
Chiaro, Christopher
Hafer, Kelsey T.
Gandhi, Ujjawal H.
Thompson, Jerry T.
van den Heuvel, John P.
Kennett, Mary J.
Hankey, Pamela
Paulson, Robert F.
Prabhu, K. Sandeep

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