Research article summary (published 18 Aug 2009):

Hydrostatic pressure-dependent changes in cyclic AMP signaling in optic nerve head astrocytes from Caucasian and African American donors.

Full Abstract

PURPOSE: Investigate the effect of hydrostatic pressure (HP) on 3', 5'-cyclic adenosine monophosphate (cAMP) levels and downstream signaling in cultures of normal optic nerve head (ONH) astrocytes from Caucasian American (CA) and African American (AA) donors. METHODS: Intracellular cAMP levels were assayed after exposing ONH astrocytes to HP for varying times. Quantitative RT-PCR was used to determine the expression levels of selected cAMP pathway genes in human ONH astrocytes after HP treatment. Western blots were used to measure changes in the phosphorylation state of cAMP response element binding protein (CREB) in astrocytes subjected to HP, ATP, and phosphodiesterase or kinase inhibitors. RESULTS: The basal intracellular cAMP level is similar among AA and CA astrocytes. After exposure to HP for 15 min and 30 min in the presence of a phosphodiesterase inhibitor a further increase of intracellular cAMP was observed in AA astrocytes, but not in CA astrocytes. Consistent with activation of the cAMP-dependent protein kinase pathway, CREB phosphorylation (Ser-133) was increased to a greater extent in AA than in CA astrocytes after 3 h of HP. Exposure to elevated HP for 3-6 h differentially altered the expression levels of selected cAMP pathway genes (ADCY3, ADCY9, PTHLH, PDE7B) in AA compared to CA astrocytes. Treatment with ATP increased more CREB phosphorylation in CA than in AA astrocytes, suggesting differential Ca(2+) signaling in these populations. CONCLUSIONS: Activation of the cAMP-dependent signaling pathway by pressure may be an important contributor to increased susceptibility to elevated intraocular pressure and glaucoma in AA, a population at higher risk for the disease.

Author information

Author/s: Chen, Lin (L); Lukas, Thomas J (TJ); Hernandez, M Rosario (MR);

Affiliation: Department of Ophthalmology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.

Grants: EY06416 (Agency:NEI NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Molecular vision (Mol Vis), published in United States. (Language: eng)

Reference: 2009-; vol 15 (issue ) : pp 1664-72

Dates: Created 2009/08/27; Completed 2009/10/27;

PMID: 19710943, status: MEDLINE (last retrieval date: 10/27/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adaptor Proteins, Signal Transducing - genetics; metabolism Adenosine Triphosphate - pharmacology Adenylate Cyclase - genetics; metabolism Adult African Americans Aged Astrocytes - drug effects; enzymology; metabolism Calcium Signaling - drug effects Cyclic AMP - metabolism Cyclic AMP Response Element-Binding Protein - metabolism Cyclic Nucleotide Phosphodiesterases, Type 7 - genetics; metabolism European Continental Ancestry Group Female Gene Expression Regulation - drug effects

Gene Expression Regulation - drug effects Humans Hydrostatic Pressure Isoquinolines - pharmacology Male Membrane Proteins - genetics; metabolism Middle Aged Optic Disk - cytology Parathyroid Hormone-Related Protein - genetics; metabolism Phosphorylation - drug effects RNA, Messenger - genetics; metabolism Signal Transduction - drug effects; genetics Sulfonamides - pharmacology Tissue Donors

Associated Chemicals: Adaptor Proteins, Signal Transducing (0) ; CAP2 protein, human (0) ; Cyclic AMP Response Element-Binding Protein (0) ; Isoquinolines (0) ; Membrane Proteins (0) ; PTHLH protein, human (0) ; Parathyroid Hormone-Related Protein (0) ; RNA, Messenger (0) ; Sulfonamides (0) ; H 89 (127243-85-0) ; Adenosine Triphosphate (56-65-5) ; Cyclic AMP (60-92-4) ; Cyclic Nucleotide Phosphodiesterases, Type 7 (EC 3.1.4.17) ; PDE7B protein, human (EC 3.1.4.17) ; Adenylate Cyclase (EC 4.6.1.1)

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