Altered gene expression in cerebral capillaries of stroke-prone spontaneously hypertensive rats

Brain Res. 2001 Aug 10;910(1-2):106-15. doi: 10.1016/s0006-8993(01)02670-1.

Abstract

Stroke-prone spontaneously hypertensive rats (SHRSP) are a well-characterized, genetic model for stroke. We showed earlier that the structure and function of the tight junctions in SHRSP blood-brain barrier endothelial cells is disturbed prior to stroke. To investigate the molecular events leading to endothelial dysfunction in SHRSP cerebral capillaries, we carried out suppression subtractive hybridization (SSH) in combination with a cDNA filter screening step. We identified two cDNA fragments that were upregulated in SHRSP, compared to stroke-resistant spontaneously hypertensive rats (SHR), and found open reading frames of 133 and 138 amino acids, respectively. These peptides did not match any known proteins in public databases. A third upregulated SHRSP cDNA fragment was identified as the rat sulfonylurea receptor 2B (SUR2B). We also isolated and cloned the cDNA of the rat homologue for the mouse G-protein signaling 5 (RGS5) regulator. This regulator was downregulated in SHRSP. We used in situ hybridization to show that rat RGS5 is expressed in the brain capillary endothelium and in the choroid plexus. Our findings may lead to the identification of new stroke-related genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blood-Brain Barrier / genetics
  • Causality
  • Cerebral Arteries / metabolism*
  • Cerebral Arteries / pathology
  • Cerebral Arteries / physiopathology
  • DNA, Complementary / genetics*
  • DNA, Complementary / isolation & purification
  • DNA, Complementary / metabolism
  • Endothelium, Vascular / metabolism*
  • Endothelium, Vascular / pathology
  • Endothelium, Vascular / physiopathology
  • GTP-Binding Proteins / metabolism
  • Gene Expression Regulation, Developmental / physiology*
  • Hypertension / complications
  • Hypertension / genetics
  • Hypertension / metabolism*
  • In Situ Hybridization / methods
  • Molecular Sequence Data
  • Peptide Fragments / genetics
  • Potassium Channels / genetics
  • Potassium Channels / metabolism
  • Potassium Channels, Inwardly Rectifying*
  • RGS Proteins / genetics
  • RGS Proteins / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Inbred SHR / abnormalities
  • Rats, Inbred SHR / genetics
  • Rats, Inbred SHR / metabolism*
  • Receptors, Drug / genetics
  • Receptors, Drug / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Nucleic Acid
  • Signal Transduction / physiology
  • Stroke / genetics
  • Stroke / metabolism*
  • Stroke / physiopathology
  • Sulfonylurea Receptors

Substances

  • ATP-Binding Cassette Transporters
  • Abcc9 protein, mouse
  • DNA, Complementary
  • Peptide Fragments
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • RGS Proteins
  • RNA, Messenger
  • Receptors, Drug
  • Rgs5 protein, rat
  • Sulfonylurea Receptors
  • GTP-Binding Proteins