scholarly journals Human Recombinant Leptin Shows Dose and Time-Dependent Release of Nitric Oxide from Endothelial Nitric Oxide Synthase in Endothelium While on Angiogenesis

Author(s):  
Reji Manjunathan ◽  
Swaraj Sinha ◽  
Akila Swaminathan ◽  
Dharanibalan Kasiviswanathan ◽  
Malathi Ragunathan ◽  
...  

Abstract Nitric Oxide (NO) modulates various assortments of the angiogenic process. The endogenous hormone leptin is able to induce different physiological process such as angiogenesis at low concentration because of its high receptor specific affinity. Various studies speculated leptin’s ability to induce endothelium‐dependent vascular relaxation by stimulating NO through different signaling pathways. So far, no studies have reported the dose and time dependent potential of human recombinant leptin on NO release. Hence, an attempt has been made to understand the optimal concentration and time of incubation of human recombinant leptin for the enzymatic release of NO from endothelial Nitric Oxide Synthase (eNOS). Leptin induced changes in the localization and phosphorylation pattern of eNOS in cultured endothelium under various concentrations and time of incubation is studied. The 5 Nanomolar concentration of human recombinant leptin within 6 minutes of incubation could induce significant levels of NO from the activated eNOS in cultured endothelium through plasma membrane localization and phosphorylation of eNOS. Our findings suggest that human recombinant leptin can modulate NO-dependent new therapeutic avenue for angiogenesis-related disorders such as wound healing if used within the active concentration and time of incubation.

Author(s):  
Chi-Ming Wei ◽  
Margarita Bracamonte ◽  
Shi-Wen Jiang ◽  
Richard C. Daly ◽  
Christopher G.A. McGregor ◽  
...  

Nitric oxide (NO) is a potent endothelium-derived relaxing factor which also may modulate cardiomyocyte inotropism and growth via increasing cGMP. While endothelial nitric oxide synthase (eNOS) isoforms have been detected in non-human mammalian tissues, expression and localization of eNOS in the normal and failing human myocardium are poorly defined. Therefore, the present study was designed to investigate eNOS in human cardiac tissues in the presence and absence of congestive heart failure (CHF).Normal and failing atrial tissue were obtained from six cardiac donors and six end-stage heart failure patients undergoing primary cardiac transplantation. ENOS protein expression and localization was investigated utilizing Western blot analysis and immunohistochemical staining with the polyclonal rabbit antibody to eNOS (Transduction Laboratories, Lexington, Kentucky).


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