Differential Expression and Cellular Distribution of gamma-Tubulin and beta III-Tubulin in Medulloblastomas and Human Medulloblastoma Cell Lines
ring; Physiology; Cell Biology; complex; mammalian-cells; monoclonal-antibodies; candidate genes; cerebellar medulloblastomas; kinesin-like protein; microtubule nucleation; mitotic spindle; pale islands; posttranslational modification
In previous studies, we have shown overexpression and ectopic subcellular distribution of gamma-tubulin and beta III-tubulin in human glioblastomas and glioblastoma cell lines (Katsetos et al., 2006,] Neuropathol Exp Neurol 65:455-467; Katsetos et al., 2007, Neurochem Res 32:1387-1398). Here we determined the expression of gamma-tubulin in surgically excised medulloblastomas (n = 20) and in the human medulloblastoma cell lines D283 Med and DAOY. In clinical tissue samples, the immunohistochemical distribution of gamma-tubulin labeling was pervasive and inversely related to neuritogenesis. Overexpression of gamma-tubulin was widespread in poorly differentiated, proliferating tumor cells but was significantly diminished in quiescent differentiating tumor cells undergoing neuritogenesis, highlighted by beta III-tubulin immunolabeling. By quantitative real-time PCR, gamma-tubulin transcripts for TUBG1, TUBG2, and TUBB3 genes were detected in both cell lines but expression was less prominent when compared with the human glioblastoma cell lines. Immunoblotting revealed comparable amounts of gamma-tubulin and beta III-tubulin in different phases of cell cycle; however, a larger amount of gamma-tubulin was detected in D283 Med when compared with DAOY cells. Interphase D283 Med cells exhibited predominantly diffuse cytoplasmic gamma-tubulin localization, in addition to the expected centrosome-associated distribution. Robust beta III-tubulin immunoreactivity was detected in mitotic spindles of DAOY cells. Our data indicate that overexpression of gamma-tubulin may be linked to phenotypic dedifferentiation (anaplasia) and tumor progression in medulloblastomas and may potentially serve as a promising tumor marker. J. Cell. Physiol. 223: 519-529,2010. (C) 2010 Wiley-Liss, Inc.
Caracciolo V; D'Agostino L; Draberova E; Sladkova V; Crozier-Fitzgerald C; Agamanolis D P; De Chadarevian J P; Legido A; Giordano A; Draber P; Katsetos C D
Journal of Cellular Physiology
2010
2010-05
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1002/jcp.22077" target="_blank" rel="noreferrer noopener">10.1002/jcp.22077</a>
Fenofibrate Differentially Regulates Plasminogen Activator Inhibitor-1 Gene Expression via Adenosine Monophosphate-Activated Protein Kinase-Dependent Induction of Orphan Nuclear Receptor Small Heterodimer Partner
cells; binding; complex; fibrosis; Gastroenterology & Hepatology; promoter; beta; mechanisms; pai-1; shp; smad3
Plasminogen activator inhibitor type I (PAI-1) is a marker of the fibrinolytic system and serves as a possible predictor for hepatic metabolic syndromes. Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPAR alpha) agonist, is a drug used for treatment of hyperlipidemia. Orphan nuclear receptor small heterodimer partner (SHP) plays a key role in transcriptional repression of crucial genes involved in various metabolic pathways. In this Study, we show that fenofibrate increased SHP gene expression in cultured liver cells and in the normal and diabetic mouse liver by activating the adenosine monophosphate-activated protein kinase (AMPK signaling pathway in a PPAR alpha-independent manner. Administration of transforming growth factor beta (TGF-beta) or a methionine-deficient and choline-deficient (MCD) diet to induce the progressive fibrosing steatohepatitis model in C57BL/6 mice was significantly reversed by fenofibrate via AMPK-mediated induction of SHP gene expression with a dramatic decrease in PAI-1 messenger RNA (mRNA) and protein expression along with other fibrotic marker genes. No reversal was observed in SHP null mice treated with fenofibrate. Treatment with another PPAR alpha agonist, WY14643, showed contrasting effects on these marker gene expressions in wild-type and SHP null mice, demonstrating the specificity of fenofibrate in activating AMPK signaling. Fenofibrate exhibited a differential inhibitory pattern on PAI-1 gene expression depending on the transcription factors inhibited by SHP. Conclusion: By demonstrating that a PPAR alpha-independent fenofibrate-AMPK-SHP regulatory cascade can play a key role in PAI-1 gene down-regulation and reversal of fibrosis, our study suggests that various AMPK activators regulating SHP might provide a novel pharmacologic option in ameliorating hepatic metabolic syndromes. (HEPATOLOGY 2009;50:880-892.)
Chanda D; Lee C H; Kim Y H; Noh J R; Kim D K; Park J H; Hwang J H; Lee M R; Jeong K H; Lee I K; Kweon G R; Shong M; Oh G T; Chiang J Y L; Choi H S
Hepatology
2009
2009-09
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1002/hep.23049" target="_blank" rel="noreferrer noopener">10.1002/hep.23049</a>
Pili Torti: Clinical Findings, Associated Disorders, and New Insights Into Mechanisms of Hair Twisting
Dermatology; disease; complex; defects; mutations; bcs1l gene
Pili torti is a hair shaft disorder characterized by hair that does not grow long and is easily broken; the hair often has a coarse or spangled appearance. A diagnosis is made by light microscopy of flattened hair twisted 180 degrees along its axis. Although pili torti may be isolated, it is commonly associated with other congenital defects and therefore, if identified, further evaluation for possible neurologic deficits and ectodermal disorders is an important part of the clinical evaluation. Alterations of the inner root sheath likely lead to the abnormal molding and twisting of the hair shaft. More recent research suggests that these alterations may occur in the face of mitochondrial dysfunction and may be influenced by the presence of reactive oxygen species. Cutis. 2009;84: 143-147.
Mirmirani P; Samimi S S; Mostow E
Cutis
2009
2009-09
Journal Article or Conference Abstract Publication
n/a
Effect Of Ethidium On The Morphology, Antiviral Activity And Subcellular-distribution Of Poly R(a-u)
agents; binding; Cell Biology; complex; delivery; dna; double-stranded-rna; human interferon; induction; inhibition; microscopy
Jamison J M; Gilloteaux J J; Adrian M; Summers J L
Cell Biology International
1993
1993-12
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1006/cbir.1993.1042" target="_blank" rel="noreferrer noopener">10.1006/cbir.1993.1042</a>