PMID- 20889972
OWN - NLM
STAT- MEDLINE
DCOM- 20110110
LR  - 20220309
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 285
IP  - 50
DP  - 2010 Dec 10
TI  - Dipetalodipin, a novel multifunctional salivary lipocalin that inhibits platelet 
      aggregation, vasoconstriction, and angiogenesis through unique binding 
      specificity for TXA2, PGF2alpha, and 15(S)-HETE.
PG  - 39001-12
LID - 10.1074/jbc.M110.152835 [doi]
AB  - Dipetalodipin (DPTL) is an 18 kDa protein cloned from salivary glands of the 
      triatomine Dipetalogaster maxima. DPTL belongs to the lipocalin superfamily and 
      has strong sequence similarity to pallidipin, a salivary inhibitor of 
      collagen-induced platelet aggregation. DPTL expressed in Escherichia coli was 
      found to inhibit platelet aggregation by collagen, U-46619, or arachidonic acid 
      without affecting aggregation induced by ADP, convulxin, PMA, and ristocetin. An 
      assay based on incubation of DPTL with small molecules (e.g. prostanoids, 
      leukotrienes, lipids, biogenic amines) followed by chromatography, mass 
      spectrometry, and isothermal titration calorimetry showed that DPTL binds with 
      high affinity to carbocyclic TXA(2), TXA(2) mimetic (U-46619), TXB(2), PGH(2) 
      mimetic (U-51605), PGD(2,) PGJ(2), and PGF(2alpha). It also interacts with 
      15(S)-HETE, being the first lipocalin described to date to bind to a derivative 
      of 15-lipoxygenase. Binding was not observed to other prostaglandins (e.g. 
      PGE(1), PGE(2), 8-iso-PGF(2alpha), prostacyclin), leukotrienes (e.g. LTB(4), LTC(4), 
      LTD(4), LTE(4)), HETEs (e.g. 5(S)-HETE, 12(S)-HETE, 20-HETE), lipids (e.g. 
      arachidonic acid, PAF), and biogenic amines (e.g. ADP, serotonin, epinephrine, 
      norepinephrine, histamine). Consistent with its binding specificity, DPTL 
      prevents contraction of rat uterus stimulated by PGF(2alpha) and induces relaxation 
      of aorta previously contracted with U-46619. Moreover, it inhibits angiogenesis 
      mediated by 15(S)-HETE and did not enhance inhibition of collagen-induced 
      platelet aggregation by SQ29548 (TXA(2) antagonist) and indomethacin. A 3-D model 
      for DPTL and pallidipin is presented that indicates the presence of a conserved 
      Arg(39) and Gln(135) in the binding pocket of both lipocalins. Results suggest 
      that DPTL blocks platelet aggregation, vasoconstriction, and angiogenesis through 
      binding to distinct eicosanoids involved in inflammation.
FAU - Assumpcao, Teresa C F
AU  - Assumpcao TC
AD  - Vector Biology Section, Laboratory of Malaria and Vector Research, NIAID, 
      National Institutes of Health, Bethesda, Maryland 20892-8132, USA.
FAU - Alvarenga, Patricia H
AU  - Alvarenga PH
FAU - Ribeiro, Jose M C
AU  - Ribeiro JM
FAU - Andersen, John F
AU  - Andersen JF
FAU - Francischetti, Ivo M B
AU  - Francischetti IM
LA  - eng
GR  - Z01 AI000810-11/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20101002
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Hydroxyeicosatetraenoic Acids)
RN  - 0 (Insect Proteins)
RN  - 0 (Lipocalins)
RN  - 0 (dipetalodipin protein, Dipetalogaster maxima)
RN  - 57576-52-0 (Thromboxane A2)
RN  - 73945-47-8 (15-hydroxy-5,8,11,13-eicosatetraenoic acid)
RN  - B7IN85G1HY (Dinoprost)
SB  - IM
MH  - Animals
MH  - Aorta/drug effects/metabolism
MH  - Dinoprost/*metabolism
MH  - Female
MH  - Horses
MH  - Hydroxyeicosatetraenoic Acids/*chemistry
MH  - Insect Proteins/*chemistry
MH  - Lipocalins/chemistry/*metabolism
MH  - *Neovascularization, Pathologic
MH  - Platelet Aggregation/*drug effects
MH  - Rats
MH  - Rats, Wistar
MH  - Saliva/*metabolism
MH  - Salivary Glands/metabolism
MH  - Thromboxane A2/*metabolism
MH  - Triatominae/*metabolism
MH  - Uterus/drug effects
MH  - *Vasoconstriction
PMC - PMC2998087
EDAT- 2010/10/05 06:00
MHDA- 2011/01/11 06:00
PMCR- 2011/12/10
CRDT- 2010/10/05 06:00
PHST- 2010/10/05 06:00 [entrez]
PHST- 2010/10/05 06:00 [pubmed]
PHST- 2011/01/11 06:00 [medline]
PHST- 2011/12/10 00:00 [pmc-release]
AID - S0021-9258(20)60600-7 [pii]
AID - M110.152835 [pii]
AID - 10.1074/jbc.M110.152835 [doi]
PST - ppublish
SO  - J Biol Chem. 2010 Dec 10;285(50):39001-12. doi: 10.1074/jbc.M110.152835. Epub 
      2010 Oct 2.