Hyperphosphorylation of CREB in human dopaminergic neurons: a kinetic study of cellular distribution of total CREB and phospho-CREB following oxidative stress

This source preferred by Rick Stafford

This data was imported from PubMed:

Authors: Ahmed, B.Y., Husnain, O., Stafford, R., Howard, M., Gujar, A.S., Moradiya, V., Patel, K.K. and Sihotra, S.

Journal: Neuroreport

Volume: 24

Issue: 13

Pages: 757-762

eISSN: 1473-558X

DOI: 10.1097/WNR.0b013e328364d616

The neurotoxin, 6-hydroxy dopamine (6-OHDA)-induced oxidative stress causes alterations in intracellular signalling events and activates cellular and molecular mechanisms leading to the degeneration of the dopamine-containing neurons (DCNs). The cyclic-AMP response element-binding protein (CREB) modulates the transcription of mitochondrial and nuclear genes upon phosphorylation. However, oxidative stress disrupts CREB functions and inhibits CREB signalling pathways. We have measured the activities and levels of both total CREB and its phosphorylated form (phospho-CREB) in cytosolic, mitochondrial and nuclear compartments in control (untreated) and stressed (6-OHDA-treated) DCN, differentiated from the ReNVM cell line (dDCN) at 0, 24 and 72 h time points following oxidative stress. Our results indicate that CREB phosphorylation occurs in all three subcellular locations. It further shows significant disruption of the phosphorylation process by 6-OHDA treatment and shows tridirectional trafficking of total CREB and phospho-CREB between cytosol, mitochondria and nucleus following oxidative stress induced by 6-OHDA treatment. In conclusion, our results indicate the presence of specific signalling molecules in all the compartments studied and their involvement in the signal transduction processes, where total CREB and phospho-CREB levels and activities are either upregulated or downregulated to balance each other for their roles.

This data was imported from Scopus:

Authors: Ahmed, B.Y., Husnain, O., Stafford, R., Howard, M., Gujar, A.S., Moradiya, V., Patel, K.K. and Sihotra, S.

Journal: NeuroReport

Volume: 24

Issue: 13

Pages: 757-762

eISSN: 1473-558X

ISSN: 0959-4965

DOI: 10.1097/WNR.0b013e328364d616

The neurotoxin, 6-hydroxy dopamine (6-OHDA)-induced oxidative stress causes alterations in intracellular signalling events and activates cellular and molecular mechanisms leading to the degeneration of the dopamine-containing neurons (DCNs). The cyclic-AMP response element-binding protein (CREB) modulates the transcription of mitochondrial and nuclear genes upon phosphorylation. However, oxidative stress disrupts CREB functions and inhibits CREB signalling pathways. We have measured the activities and levels of both total CREB and its phosphorylated form (phospho-CREB) in cytosolic, mitochondrial and nuclear compartments in control (untreated) and stressed (6-OHDA-treated) DCN, differentiated from the ReNVM cell line (dDCN) at 0, 24 and 72 h time points following oxidative stress. Our results indicate that CREB phosphorylation occurs in all three subcellular locations. It further shows significant disruption of the phosphorylation process by 6-OHDA treatment and shows tridirectional trafficking of total CREB and phospho-CREB between cytosol, mitochondria and nucleus following oxidative stress induced by 6-OHDA treatment. In conclusion, our results indicate the presence of specific signalling molecules in all the compartments studied and their involvement in the signal transduction processes, where total CREB and phospho-CREB levels and activities are either upregulated or downregulated to balance each other for their roles. © 2013 Wolters Kluwer Health / Lippincott.

This data was imported from Web of Science (Lite):

Authors: Ahmed, B.Y., Husnain, O., Stafford, R., Howard, M., Gujar, A.S., Moradiya, V., Patel, K.K. and Sihotra, S.

Journal: NEUROREPORT

Volume: 24

Issue: 13

Pages: 757-762

ISSN: 0959-4965

DOI: 10.1097/WNR.0b013e328364d616

This data was imported from Europe PubMed Central:

Authors: Ahmed, B.Y., Husnain, O., Stafford, R., Howard, M., Gujar, A.S., Moradiya, V., Patel, K.K. and Sihotra, S.

Journal: Neuroreport

Volume: 24

Issue: 13

Pages: 757-762

eISSN: 1473-558X

ISSN: 0959-4965

The neurotoxin, 6-hydroxy dopamine (6-OHDA)-induced oxidative stress causes alterations in intracellular signalling events and activates cellular and molecular mechanisms leading to the degeneration of the dopamine-containing neurons (DCNs). The cyclic-AMP response element-binding protein (CREB) modulates the transcription of mitochondrial and nuclear genes upon phosphorylation. However, oxidative stress disrupts CREB functions and inhibits CREB signalling pathways. We have measured the activities and levels of both total CREB and its phosphorylated form (phospho-CREB) in cytosolic, mitochondrial and nuclear compartments in control (untreated) and stressed (6-OHDA-treated) DCN, differentiated from the ReNVM cell line (dDCN) at 0, 24 and 72 h time points following oxidative stress. Our results indicate that CREB phosphorylation occurs in all three subcellular locations. It further shows significant disruption of the phosphorylation process by 6-OHDA treatment and shows tridirectional trafficking of total CREB and phospho-CREB between cytosol, mitochondria and nucleus following oxidative stress induced by 6-OHDA treatment. In conclusion, our results indicate the presence of specific signalling molecules in all the compartments studied and their involvement in the signal transduction processes, where total CREB and phospho-CREB levels and activities are either upregulated or downregulated to balance each other for their roles.

The data on this page was last updated at 04:40 on August 18, 2017.