LPA (lysophosphatidic acid) is a lipid mediator that stimulates cell proliferation and growth, and is involved in physiological and pathological processes such as wound healing, platelet activation, angiogenesis and the growth of tumours. Therefore defining the mechanisms of LPA production and degradation are of interest in understanding the regulation of these processes. Extracellular LPA synthesis is relatively well understood, whereas the mechanisms of its degradation are not. One route of LPA degradation is dephosphorylation. A candidate enzyme is the integral membrane exophosphatase LPP1 (lipid phosphate phosphohydrolase type 1). In the present paper, we report the development of a mouse wherein the LPP1 gene (Ppap2a) was disrupted. The homozygous mice, which are phenotypically unremarkable, generally lack Ppap2a mRNA, and multiple tissues exhibit a substantial (35–95%) reduction in LPA phosphatase activity. Compared with wild-type littermates, Ppap2atr/tr animals have increased levels of plasma LPA, and LPA injected intravenously is metabolized at a 4-fold lower rate. Our results demonstrate that LPA is rapidly metabolized in the bloodstream and that LPP1 is an important determinant of this turnover. These results indicate that LPP1 is a catabolic enzyme for LPA in vivo.
Skip Nav Destination
Article navigation
May 2009
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Research Article|
April 14 2009
Lipid phosphate phosphohydrolase type 1 (LPP1) degrades extracellular lysophosphatidic acid in vivo
Jose L. Tomsig;
Jose L. Tomsig
*Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, U.S.A.
Search for other works by this author on:
Ashley H. Snyder;
Ashley H. Snyder
*Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, U.S.A.
Search for other works by this author on:
Evgeny V. Berdyshev;
Evgeny V. Berdyshev
†Department of Medicine, Biological Sciences Division, University of Chicago, Chicago, IL 60637, U.S.A.
Search for other works by this author on:
Anastasia Skobeleva;
Anastasia Skobeleva
†Department of Medicine, Biological Sciences Division, University of Chicago, Chicago, IL 60637, U.S.A.
Search for other works by this author on:
Chifundo Mataya;
Chifundo Mataya
‡Department of Biochemistry, University of Alberta, Edmonton, Canada, T6G 2S2
Search for other works by this author on:
Viswanathan Natarajan;
Viswanathan Natarajan
†Department of Medicine, Biological Sciences Division, University of Chicago, Chicago, IL 60637, U.S.A.
Search for other works by this author on:
David N. Brindley;
David N. Brindley
‡Department of Biochemistry, University of Alberta, Edmonton, Canada, T6G 2S2
Search for other works by this author on:
Kevin R. Lynch
Kevin R. Lynch
1
*Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, U.S.A.
1To whom correspondence should be addressed (email krl2z@virginia.edu).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
September 16 2008
Revision Received:
February 02 2009
Accepted:
February 12 2009
Accepted Manuscript online:
February 12 2009
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2009 Biochemical Society
2009
Biochem J (2009) 419 (3): 611–618.
Article history
Received:
September 16 2008
Revision Received:
February 02 2009
Accepted:
February 12 2009
Accepted Manuscript online:
February 12 2009
Citation
Jose L. Tomsig, Ashley H. Snyder, Evgeny V. Berdyshev, Anastasia Skobeleva, Chifundo Mataya, Viswanathan Natarajan, David N. Brindley, Kevin R. Lynch; Lipid phosphate phosphohydrolase type 1 (LPP1) degrades extracellular lysophosphatidic acid in vivo. Biochem J 1 May 2009; 419 (3): 611–618. doi: https://doi.org/10.1042/BJ20081888
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.