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Aspects of the transcriptional and translational regulation of nitric oxide synthase 1

Pierson, Shawn M
http://rave.ohiolink.edu/etdc/view?acc_num=osu1111595828

Abstract Details

2005, Doctor of Philosophy, Ohio State University, Pharmacy.
The nitric oxide synthases (NOS) catalyze the formation of nitric oxide (NO) and citrulline from the reactants arginine and oxygen. Three isoforms of the enzyme have been discovered and designated NOS1, NOS2 and NOS3. NO produced by NOS1 plays a role in a variety of physiological processes including learning and memory, bronchial relaxation and GI motility. Excessive production of NO can be toxic to neurons and is associated with various pathophysiological conditions. This dissertation explores the regulation of the gene encoding for NOS1 in order to gain insights into its normal and abnormal regulation. Using PC12 cells, we studied the effect the peptide pituitary derived adenylate cyclase activating peptide (PACAP38), a 38 amino acid peptide hormone, had on endogenous NOS1 expression. We showed that PACAP led to an increase in both NOS1 mRNA and protein. Further, it was demonstrated that the transcript upregulated was a shortened transcript driven by a promoter located in what is normally exon 2. We next looked at the effect of PACAP38 had on the rat and human exon 2 promoters. We showed both of these promoters were stimulated by PACAP and required the activation of multiple signal transduction pathways for full activation. We next looked at the effect of PACAP38 on another human NOS1 promoter, the 5’2(1F) promoter. We demonstrated that the activation of the cAMP-PKA pathway was totally responsible for activation of this promoter by PACAP38. We then mapped the region of 5’2 necessary for PACAP stimulation to a 230 base pair region just upstream of the 5’2 alternate first exon and that a single CRE site within this region was essential for PACAP38 stimulation. Lastly, we cloned and characterized two novel promoters of NOS1. The first promoter drives the expression of a NOS1 transcript containing a novel alternate first exon discovered by Greg Hartt working in our lab. This exon was designated 5’3 by us and 1D by others. The second promoter drives the expression of a transcript containing a second alternate first exon discovered by Dr Hartt and designated 5’4 by us and 1C by others.
Anthony Young (Advisor)
156 p.
nNOS; NOS1; Nitric oxide synthase 1; alternate first exons; PACAP; pituitary adenylate cyclase activating peptide

Recommended Citations

Citations

  • Pierson, S. M. (2005). Aspects of the transcriptional and translational regulation of nitric oxide synthase 1 [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1111595828

    APA Style (7th edition)

  • Pierson, Shawn. Aspects of the transcriptional and translational regulation of nitric oxide synthase 1. 2005. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1111595828.

    MLA Style (8th edition)

  • Pierson, Shawn. "Aspects of the transcriptional and translational regulation of nitric oxide synthase 1." Doctoral dissertation, Ohio State University, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=osu1111595828

    Chicago Manual of Style (17th edition)

osu1111595828
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© 2005, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.