Ukr.Biochem.J. 2018; Том 90, № 3, травень-червень, c. 49-61

doi: https://doi.org/10.15407/ubj90.03.049

IRE1 змінює ефект дефіциту глутаміну на експресію факторів росту пухлин у клітинах гліоми лінії U87

10.05.2018   Без категорії   No comments

О. Г. Мінченко, А. П. Харькова, О. С. Гнатюк,
О. Я. Лузіна, І. В. Кривдюк, А. Ю. Кузнєцова

Інститут біохімії ім. О. В. Палладіна НАН України, Київ;
e-mail: ominchenko@yahoo.com

У роботі досліджували експресію групи генів, що кодують важливі протеїни в клітинах гліоми лінії U87 в умовах пригнічення функції ERN1 (endoplasmic reticulum to nucleus signaling 1) та дефіциту глутаміну. Показано, що за умов дефіциту глутаміну знижувався рівень експресії мРНК ATF6 (activating transcription factor 6), EIF2AK3/PERK (eukaryotic translation initiation factor 2 alpha kinase 3), GLO1 (glyoxalase I), BIRC5 (baculoviral IAP repeat-containing 5) та RAB5C (RAB5C, a member of RAS oncogene family) в контрольних клітинах гліоми. В той самий час, рівень експресії мРНК HSPB8 (heat shock 22 kDa protein 8) та HSPA5/GRP78 (heat shock protein family A (Hsp70) member 5) був резистентним до дефіциту глутаміну в цих клітинах гліоми. Пригнічення ERN1 модифікувало ефект дефіциту глутаміну на рівень експресії більшості досліджених генів у клітинах гліоми лінії U87: збільшувало експресію генів ATF6 і HSPA5 та посилювало чутливість генів EIF2AK3 і BIRC5 до дефіциту глутаміну. Більше того, експресія досліджених генів (за винятком EIF2AK3) знижувалася в клітинах гліоми з пригніченим ERN1 у присутності глутаміну. Показано, що дефіцит глутаміну змінює експресію більшості досліджених генів залежно від ERN1 і ці зміни, можливо, причетні до пригнічення росту гліом із клітин без функціональної активності сигнального ензиму ERN1.

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