Prostatic acid phosphatase degrades lysophosphatidic acid in seminal plasma.
Lysophosphatidic acid (LPA) is a lipid mediator with multiple biological activities and is detected in various biological fluids, including human seminal plasma. Due to its cell proliferation stimulatory and anti-apoptotic activities, LPA has been implicated in the progression of some cancers such as ovarian cancer and prostate cancer. Here, we show that prostatic acid phosphatase, which is a non-specific phosphatase and which has been implicated in the progression of prostate cancer, inactivates LPA in human seminal plasma. Human seminal plasma contains both an LPA-synthetic enzyme, lysoPLD, which converts lysophospholipids to LPA and is responsible for LPA production in serum, and its major substrate, lysophosphatidylcholine. In serum, LPA accumulated during incubation at 37 degrees C. However, in seminal plasma, LPA did not accumulate. This discrepancy is explained by the presence of a strong LPA-degrading activity. Incubation of LPA with seminal plasma resulted in the disappearance of LPA and an accompanying accumulation of monoglyceride showing that LPA is degraded by phosphatase activity present in the seminal plasma. When seminal plasma was incubated in the presence of a phosphatase inhibitor, sodium orthovanadate, LPA accumulated, indicating that LPA is produced and degraded in the fluid. Biochemical characterization of the LPA-phosphatase activity identified two phosphatase activities in human seminal plasma. By Western blotting analysis in combination with several column chromatographies, the major activity was revealed to be identical to prostatic acid phosphatase. The present study demonstrates active LPA metabolism in seminal plasma and indicates the possible role of LPA signaling in male sexual organs including prostate cancer.
Tanaka
Masayuki
M
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Kishi
Yasuhiro
Y
Takanezawa
Yasukazu
Y
Kakehi
Yoshiyuki
Y
Aoki
Junken
J
Arai
Hiroyuki
H
D000135:Acid Phosphatase; D000328:Adult; D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D004492:Edetic Acid / Q000494:pharmacology; D006709:Homoarginine / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008246:Lysophospholipids / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010744:Phosphoric Monoester Hydrolases / Q000097:blood / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000097:blood / Q000378:metabolism*; D012661:Semen / Q000201:enzymology*; D013379:Substrate Specificity; D014638:Vanadates / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D008246:Lysophospholipids; D006709:Homoarginine; D014638:Vanadates; D004492:Edetic Acid; C076020:lysophosphatidic acid phosphatase; D000135:Acid Phosphatase; D010744:Phosphoric Monoester Hydrolases; C428439:prostatic acid phosphatase; D017027:Protein Tyrosine Phosphatases; C032881:lysophosphatidic acid