Modulation of parkin gene expression in noradrenergic neuronal cells.
Typical autosomal recessive juvenile Parkinsonism (AR-JP) is resulted from the loss of function mutation in the parkin gene. In an effort to learn more about the cell type-specific functional role of parkin, we used in vitro model such as locus coeruleus (LC) noradrenergic (NA) neuronal progenitor cell line, LC3541. Employing this in vitro model, we revealed that parkin plays a crucial role in phenotypic differentiation of NA neurons. Our results showed that parkin mRNA was expressed during the differentiation of NA neuronal progenitor cell line and that the level of the parkin mRNA was down-regulated by oxidative stress in the NA neuronal cells. Parkin protein overexpression in LC3541 cells induced expression of NA markers (TH, phox2a and DBH). Small interfering RNA (SiRNA) for parkin supressed NA differentiation and DBH expression. Preventing protein kinase A (PKA) activation with PKI attenuated expression of DBH in parkin overexpressed LC3541 cells. These findings suggest that the relative abundance of parkin enhances differentiation of NA phenotypes via a PKA-dependent pathway.
Park
Euteum
E
Department of Biotechnology (BK21 Program), Chosun University, Gwangju 501-759, Republic of Korea.
Kim
Seung
S
Kim
Sung-Jun
SJ
Park
Yeol
Y
Lee
Jung-Sup
JS
Yoo
Jin-Cheol
JC
Kim
Chun-Sung
CS
Kim
Do Kyung
DK
Lee
Sook-Young
SY
Chun
Hong Sung
HS
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004299:Dopamine beta-Hydroxylase / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008125:Locus Coeruleus / Q000166:cytology / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000502:physiology*; D009638:Norepinephrine / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013564:Sympathetic Nervous System / Q000502:physiology*; D014162:Transfection; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
D012333:RNA, Messenger; D034741:RNA, Small Interfering; D004299:Dopamine beta-Hydroxylase; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D017868:Cyclic AMP-Dependent Protein Kinases; D009638:Norepinephrine