Enhancing the GLP-1 receptor signaling pathway leads to proliferation and neuroprotection in human neuroblastoma cells.

Enhancing the GLP-1 receptor signaling pathway leads to proliferation and neuroprotection in human neuroblastoma cells.

J Neurochem. 2010 Apr 2;

Authors: Li Y, Tweedie D, Mattson MP, Holloway HW, Greig NH

Abstract Increasing evidence suggests that glucagon-like peptide-1 (GLP-1), an incretin hormone of current interest in type 2 diabetes, is neuroprotective in both cell culture and animal models. To characterize the neuroprotective properties of GLP-1 and associated underlying mechanisms, we over-expressed the GLP-1 receptor (R) on human neuroblastoma SH-SY5Y cells to generate a neuronal culture system featuring enhanced GLP-1R signaling. In GLP-1R over-expressing SH-SY5Y (SH-hGLP-1R#9) cells, GLP-1 and the long-acting agonist exendin-4 (Ex-4) stimulated cell proliferation and increased cell viability by 2-fold at 24 h at physiologically relevant concentrations. This GLP-1R-dependent action was mediated via the protein kinase A (PKA) and phosphoinositide 3-kinase (PI3K) signaling pathways, with the mitogen-activated protein kinase (MAPK) pathway playing a minor role. GLP-1 and Ex-4 pretreatment dose-dependently protected SH-hGLP-1R#9 cells from hydrogen peroxide (H(2)O(2))- and 6-hydroxydopamine (6-OHDA)-induced cell death. This involved amelioration of elevated caspase-3 activity, down-regulation of pro-apoptotic Bax and up-regulation of anti-apoptotic Bcl-2 protein. In the presence of 6-OHDA, GLP-1's ability to lower caspse-3 activity was abolished with the PI3K inhibitor, LY2940002, and partly reduced with the PKA inhibitor, H89. Hence, GLP-1R mediated neurotrophic and anti-apoptotic actions co-contribute to the neuroprotective property of GLP-1 in neuronal cell cultures, and reinforce the potential therapeutic value of GLP-1R agonists in neurodegenerative disorders involving oxidative stress.

PMID: 20374430 [PubMed - as supplied by publisher]

Read the complete post at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?tmpl=NoSidebarfile&db=PubMed&cmd=Retrieve&list_uids=20374430&dopt=Abstract

Posted 9 Apr 2010 3:20 AM by pubmed: neuroblastoma
Filed under:

Seten amet diorl oprta ahsellu miokiste porta.

Bean nonumy hendrit mauris phelus porta. Fusce suscipit varius ui. Fusce feugiat malesada odio. Morbi nunc odio, gravida sit cursusnec, luctus aorem. auris phelus porta ae. Fusce suscipit varius ui. Fusce feug.

Read More

There is nothing quite as devastating as hearing that word - neuroblastoma. In seconds your world is turned upside down and your normal life is but a distant memory. You are thrust into a confusing world full of fear. Your child has cancer.

We know. We have been there. The Neuroblastoma Foundation is here for you.

Welcome to our website. It is a place for you to find answers and ask questions. One of the primary goals of the Neuroblastoma Foundation is to ensure that parents, patients and health care professionals find the information they need to make the best treatment decisions possible for children and adults affected by neuroblastoma. There is a vast amount of information throughout the internet, much of which is encapsulated in medical jargon that is so complex that even many medical professionals have difficulty in interpreting its meaning. We are here to help to decipher this information and to make sure you (and your oncologist) understand exactly what it means to you. From treatment decisions to side effects we have parents and experts that have experienced it all and are willing to distill it for you.