title: Expression changes of genes associated with apoptosis and survival processes in Parkinson's disease.
abstract: Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive degeneration of the dopaminergic neurons in substantia nigra, presumably due to increased apoptosis and oxidative stress. To investigate whether PD-induced survival/apoptosis gene expression changes can serve as prognostic biomarkers of PD, we measured expression levels of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt pathway factors and additional apoptotic and anti-apoptotic factors in peripheral blood mononuclear cells (PBMC) of PD patients (n=50) and healthy controls (n=50) by real time PCR. Expression levels of apoptotic factors phosphatase and tensin homolog (PTEN) and mitochondrial apoptosis-inducing factor 1 (AIFM1) were significantly decreased, anti-apoptotic factors DJ-1 and Akt-1 were significantly increased and anti-apoptotic Bcl-2 was significantly decreased in PD patients. Expression levels of AIFM1 were significantly correlated with Hoehn-Yahr scores. Moreover, PD patients with postural instability showed significantly reduced expression levels of anti-apoptotic DJ-1, Akt-1 and mTOR than PD patients without postural instability. Expression profiles of brain samples of mice with rotenone-induced PD model and PBMC samples of PD patients showed remarkable resemblance. Our results indicate that the anti-apoptotic PI3K/Akt pathway is over activated in PD, presumably as an effort to compensate for increased neuronal apoptosis and oxidative stress. By contrast, patients with postural instability show reduced anti-apoptotic factor expression suggesting that this compensating mechanism fails in patients with this particular motor symptom. PBMC expression levels of AIFM1 might serve as a biomarker of disability and disease progression in PD.
authors.affiliation: Department of Neuroscience, Institute for Experimental Medical Research (DETAE), Istanbul University, Istanbul, Turkey.
authors.forename: Nazli
authors.initials: N
authors.lastname: Yalçınkaya
authors.affiliation: Department of Neuroscience, Institute for Experimental Medical Research (DETAE), Istanbul University, Istanbul, Turkey.
authors.forename: Hazal
authors.initials: H
authors.lastname: Haytural
authors.affiliation: Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Başar
authors.initials: B
authors.lastname: Bilgiç
authors.affiliation: Department of Genetics, Institute for Experimental Medical Research (DETAE), Istanbul University, Istanbul, Turkey.
authors.forename: Özkan
authors.initials: Ö
authors.lastname: Özdemir
authors.affiliation: Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Haşmet
authors.initials: H
authors.lastname: Hanağası
authors.affiliation: Department of Neuroscience, Institute for Experimental Medical Research (DETAE), Istanbul University, Istanbul, Turkey.
authors.forename: Cem İsmail
authors.initials: Cİ
authors.lastname: Küçükali
authors.affiliation: Department of Biochemistry, Eyup State Hospital, Istanbul, Turkey.
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Özbek
authors.affiliation: Department of Neuroscience, Institute for Experimental Medical Research (DETAE), Istanbul University, Istanbul, Turkey.
authors.forename: Uğur
authors.initials: U
authors.lastname: Akcan
authors.affiliation: Department of Genetics, Institute for Experimental Medical Research (DETAE), Istanbul University, Istanbul, Turkey.
authors.forename: Halil Atilla
authors.initials: HA
authors.lastname: İdrisoğlu
authors.affiliation: Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Hakan
authors.initials: H
authors.lastname: Gürvit
authors.affiliation: Department of Neuroscience, Institute for Experimental Medical Research (DETAE), Istanbul University, Istanbul, Turkey. Electronic address: drerdem@yahoo.com.
authors.forename: Erdem
authors.initials: E
authors.lastname: Tüzün
mesh_terms: D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D016022:Case-Control Studies; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012402:Rotenone; D015398:Signal Transduction
chemical_list: D051033:Apoptosis Inducing Factor; D015415:Biomarkers; D019253:Proto-Oncogene Proteins c-bcl-2; D012402:Rotenone; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse; D053148:Caspase 3; D053453:Caspase 9
keywords: Akt; Apoptosis; Parkinson’s; Real time PCR; Survival; disease