Diacylglycerol kinase inhibition and vascular function

Hyehun Choi, Kyan J. Allahdadi, Rita C A Tostes, R Clinton Webb

Research output: Contribution to journalReview article

3 Citations (Scopus)

Abstract

Diacylglycerol kinases (DGKs), a family of lipid kinases, convert diacylglycerol (DG) to phosphatidic acid (PA). Acting as a second messenger, DG activates protein kinase C (PKC). PA, a signaling lipid, regulates diverse functions involved in physiological responses. Since DGK modulates two lipid second messengers, DG and PA, regulation of DGK could induce related cellular responses. Currently, there are 10 mammalian isoforms of DGK that are categorized into five groups based on their structural features. These diverse isoforms of DGK are considered to activate distinct cellular functions according to extracellular stimuli. Each DGK isoform is thought to play various roles inside the cell, depending on its subcellular localization (nuclear, ER, Golgi complex or cytoplasm). In vascular smooth muscle, vasoconstrictors such as angiotensin II, endothelin-1 and norepinephrine stimulate contraction by increasing inositol trisphosphate (IP3), calcium, DG and PKC activity. Inhibition of DGK could increase DG availability and decrease PA levels, as well as alter intracellular responses, including calcium-mediated and PKC-mediated vascular contraction. The purpose of this review is to demonstrate a role of DGK in vascular function. Selective inhibition of DGK isoforms may represent a novel therapeutic approach in vascular dysfunction.

Original languageEnglish (US)
Pages (from-to)148-152
Number of pages5
JournalCurrent Enzyme Inhibition
Volume5
Issue number3
DOIs
StatePublished - Oct 21 2009

Fingerprint

Diacylglycerol Kinase
Blood Vessels
Phosphatidic Acids
Diglycerides
Protein Isoforms
Protein Kinase C
Second Messenger Systems
Lipids
Calcium
Golgi Apparatus
Vasoconstrictor Agents
Endothelin-1
Inositol
Vascular Smooth Muscle
Angiotensin II
Muscle
Norepinephrine
Cytoplasm

Keywords

  • Diacylglycerol
  • Diacylglycerol kinase
  • Phosphatidic acid
  • Protein kinase C
  • Vascular function
  • Vasoconstrictor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Drug Discovery

Cite this

Diacylglycerol kinase inhibition and vascular function. / Choi, Hyehun; Allahdadi, Kyan J.; Tostes, Rita C A; Webb, R Clinton.

In: Current Enzyme Inhibition, Vol. 5, No. 3, 21.10.2009, p. 148-152.

Research output: Contribution to journalReview article

Choi, Hyehun ; Allahdadi, Kyan J. ; Tostes, Rita C A ; Webb, R Clinton. / Diacylglycerol kinase inhibition and vascular function. In: Current Enzyme Inhibition. 2009 ; Vol. 5, No. 3. pp. 148-152.
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