Novel role of puberty onset protein kisspeptin as an anticoagulation peptide.
A peptide mainly of hypothalamus and placental origin named 'kisspeptin' suppresses metastasis of melanoma cells. As several malignant tumors lead to impaired blood coagulation, we hypothesized if kisspeptin acts also as a potential anticoagulant. The effect was studied in vivo through intraperitoneal administration of kisspeptin to laboratory rats, and application of kisspeptin ex vivo to rat and human blood. In another set of experiments, clotting factors in the form of rat fresh plasma were injected into rats' prior to kisspeptin administration. Standard anticoagulation parameters were studied through established methods and commercially available kits. Herein, we demonstrate dose-dependent anticoagulation effect following in vivo kisspeptin administration. Coagulation time, bleeding time, prothrombin time and activated partial thromboplastin time were significantly (P < 0.0002) prolonged, international normalized ratio increased, while plasma calcium concentration and mean platelet count were significantly decreased (P < 0.001). Mean platelet volume increased only at the highest tested dose while platelet distribution width remained unaltered. Where fresh plasma was administered prior to kisspeptin treatment, results were similar to kisspeptin alone treatment except for significantly (P < 0.001) increased plasma calcium concentration. Application of kisspeptin ex vivo to rat and human blood produced similar results. This is the first report on kisspeptin's role in the anticoagulation of blood and suggests that it may increase the bleeding tendency possibly via modulation of calcium-signaling or inactivating calcium action, inhibition of thrombin and quick reduction in platelet numbers. A detailed investigation of the anticoagulation role of kisspeptin would help to clarify its use as an anticoagulant and thrombolytic agent.
Department of Animal Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan. irfanzia@aqau.edu.pk
Irfan Zia
IZ
Qureshi
Sobia
S
Kanwal
D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology*; D001760:Bleeding Time; D001777:Blood Coagulation / Q000187:drug effects*; D002118:Calcium / Q000097:blood; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D059648:Kisspeptins; D010314:Partial Thromboplastin Time; D010976:Platelet Count; D011517:Prothrombin Time; D051381:Rats; D017207:Rats, Sprague-Dawley; D025521:Tumor Suppressor Proteins / Q000008:administration & dosage / Q000494:pharmacology*
D000925:Anticoagulants; C106628:KISS1 protein, human; D059648:Kisspeptins; D025521:Tumor Suppressor Proteins; D002118:Calcium