Radiation-induced upregulation of γ-glutamyltransferase in colon carcinoma cells is mediated through the Ras signal transduction pathway

The activity of γ-glutamyltransferase (GGT) is frequently upregulated in tumor cells after oxidative stress and may thus increase the availability of amino acids needed for biosynthesis of the antioxidant glutathione. As γ-radiation of tumor cells can result in oxidative stress, we investigated whet...

Celý popis

Uloženo v:

Podrobná bibliografie
Vydáno v:	Biochimica et biophysica acta Ročník 1760; číslo 2; s. 151 - 157
Hlavní autoři:	Pankiv, Serhiy, Møller, Seila, Bjørkøy, Geir, Moens, Ugo, Huseby, Nils-Erik
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Netherlands Elsevier B.V 01.02.2006
Témata:	Animals Apoptosis - radiation effects Cell Line, Tumor Colon carcinoma cell Colonic Neoplasms - enzymology Extracellular Signal-Regulated MAP Kinases - physiology Gamma Rays gamma-Glutamyltransferase - biosynthesis gamma-Glutamyltransferase - radiation effects Glutathione Humans MAP Kinase Kinase Kinases - physiology Oxidative stress Phosphatidylinositol 3-Kinases - physiology Radioactive irradiation ras Proteins - physiology Rats Reactive Oxygen Species - antagonists & inhibitors Signal Transduction - physiology Up-Regulation - radiation effects γ-glutamyltransferase Oxidative stress PI-3K JNK MAPK Radioactive irradiation MEK GGT ROS γ-glutamyltransferase Colon carcinoma cell GSH ERK Glutathione
ISSN:	0304-4165, 0006-3002, 1872-8006
On-line přístup:	Získat plný text
Tagy:	Přidat tag Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!

Popis
Shrnutí:	The activity of γ-glutamyltransferase (GGT) is frequently upregulated in tumor cells after oxidative stress and may thus increase the availability of amino acids needed for biosynthesis of the antioxidant glutathione. As γ-radiation of tumor cells can result in oxidative stress, we investigated whether such treatments modulate the enzyme level in colon carcinoma CC531 cells. Radiation of these cells blocked cell proliferation, increased cellular size, initiated apoptosis and upregulated GGT activity and protein levels in a dose- and time-related manner. A slight but significant increase in the cellular level of reactive oxygen species (ROS) was found directly after radiation but appeared not to cause the GGT elevation. Thus, other mechanisms than cellular oxidative stress appear to be responsible for the radiation-induced upregulation of GGT. Stable transfection of activated Ras in a human colon carcinoma cell line expressing wild-type Ras resulted in an increased GGT level, while a reduced enzyme level was demonstrated in another cell line with constitutively activated Ras after stably transfection with a dominant-negative Ras mutant. Moreover, addition of specific protein kinase inhibitors that blocked downstream targets PI-3K and MEK1/2 of Ras, prior to and after radiation, attenuated the radiation-induced activation of GGT. These results support a role for Ras, being frequently activated after radiation, in regulating the level of GGT and also indicate that GGT participates in radioresistance.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0304-4165 0006-3002 1872-8006
DOI:	10.1016/j.bbagen.2005.11.006