Downregulation of the α1 - and β1 -subunit of sGC in Arterial Smooth Muscle Cells of OPSCC Is HPV-Independent

Journal of Dental Research
Y KorkmazC U Huebbers

Abstract

The nitric oxide (NO)-sensitive soluble guanylyl cyclase (sGC) is a heterodimeric enzyme with an α and β subunit. NO binds to heme of the β1-subunit of sGC, activates the enzyme in the reduced heme iron state in vascular smooth muscle cells (VSMCs), and generates cGMP-inducing vasodilatation and suppression of VSMC proliferation. In the complex tumor milieu with higher levels of reactive oxygen species (ROS), sGC heme iron may become oxidized and insensitive to NO. To change sGC from an NO-insensitive to NO-sensitive state or NO-independent manner, protein expression of sGC in VSMC is required. Whether sGCα1β1 exists at the protein level in arterial VSMCs of oropharyngeal squamous cell carcinoma (OPSCC) is unknown. In addition, whether differences in the genetic profile between human papillomavirus (HPV)-positive and HPV-negative OPSCC contributes to the regulation of sGCα1β1 is unclear. Therefore, we compared the effects of HPV-positive and HPV-negative OPSCC on the expression of sGCα1β1 in arterial VSMCs from tumor-free and tumor-containing regions of human tissue sections using quantitative immunohistochemistry. In comparison to the tumor-free region, we found a decrease in expression of both α1- and β1-subunits in the arter...Continue Reading

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Citations

Jun 9, 2020·Frontiers in Pharmacology·Anida VelagicBarbara K Kemp-Harper
Aug 10, 2019·Oxidative Medicine and Cellular Longevity·Rebecca SchülerSusanne Helena Karbach
Jan 13, 2021·International Journal of Molecular Sciences·Yüksel KorkmazJames Deschner
May 15, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yang GaoDan-Li Yang

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Methods Mentioned

BETA
PCR
enzyme-linked immunosorbent assay
electrophoresis
ubiquitination

Software Mentioned

GraphPad Prism
BLAST

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