caa a22 4500 606236503 CHVBK 20210128101248.0 cr unu---uuuuu 210128e20150201xx s 000 0 eng 10.1007/s11010-014-2267-0 doi (NATIONALLICENCE)springer-10.1007/s11010-014-2267-0 Cross-talk between p38MAPK and Giα in regulating cPLA2 activity by ET-1 in pulmonary smooth muscle cells [Elektronische Daten] [Sajal Chakraborti, Animesh Chowdhury, Tapati Chakraborti] Endothelin-1 (ET-1) is known as the most potent vasoconstrictor yet described. Infusion of ET-1 into isolated rabbit lung has been shown to cause pulmonary vasoconstriction with the involvement of arachidonic acid metabolites. Given the potency of arachidonic acid metabolites, the activity of phospholipase A2 must be tightly regulated. Herein, we determined the mechanisms by which ET-1 stimulates cPLA2 activity during ET-1 stimulation of bovine pulmonary artery smooth muscle cells. We demonstrated that (i) treatment of bovine pulmonary artery smooth muscle cells with ET-1 stimulates cPLA2 activity in the cell membrane; (ii) ET-1 caused increase in O 2 ·− production occurs via NADPH oxidase-dependent mechanism; (iii) ET-1-stimulated NADPH oxidase activity is markedly prevented upon pretreatment with PKC-ζ inhibitor, indicating that PKC-ζ plays a prominent role in this scenario; (iv) ET-1-induced NADPH oxidase-derived O 2 ·− stimulates an aprotinin sensitive protease activity due to prominent increase in [Ca2+]i; (v) the aprotinin sensitive protease plays a pivotal role in activating PKC-α, which in turn phosphorylates p38MAPK and subsequently Giα leading to the activation of cPLA2. Taken together, we suggest that cross-talk between p38MAPK and Giα with the involvement of PKC-ζ, NADPH oxidase-derived O 2 ·− , [Ca2+]i, aprotinin-sensitive protease and PKC-α play a pivotal role for full activation of cPLA2 during ET-1 stimulation of pulmonary artery smooth muscle cells. Springer Science+Business Media New York, 2014 Endothelin-1 nationallicence Pulmonary artery smooth muscle cells nationallicence Protease nationallicence NADPH oxidase nationallicence Superoxide nationallicence Protien kinase C nationallicence p38 mitogen activated protein kinase nationallicence Pertussis toxin nationallicence G protein nationallicence cPLA2 : Cytosolic phospholipase A2 nationallicence ET-1 : Endothelin-1 nationallicence Giα : α-Subunit of the inhibitory G protein nationallicence [Ca2+]i : Intracellular Ca2+ nationallicence MAPK : Mitogen activated protein kinase nationallicence PKC : Protein kinase C nationallicence PLC : Phospholipase C nationallicence O 2 ·− : Superoxide anion nationallicence Chakraborti Sajal Department of Biochemistry and Biophysics, University of Kalyani, 741235, Kalyani, West Bengal, India aut Chowdhury Animesh Department of Biochemistry and Biophysics, University of Kalyani, 741235, Kalyani, West Bengal, India aut Chakraborti Tapati Department of Biochemistry and Biophysics, University of Kalyani, 741235, Kalyani, West Bengal, India aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 400/1-2(2015-02-01), 107-123 0300-8177 400:1-2<107 2015 400 11010 https://doi.org/10.1007/s11010-014-2267-0 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-014-2267-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Chakraborti Sajal Department of Biochemistry and Biophysics, University of Kalyani, 741235, Kalyani, West Bengal, India aut NATIONALLICENCE 700 1- Chowdhury Animesh Department of Biochemistry and Biophysics, University of Kalyani, 741235, Kalyani, West Bengal, India aut NATIONALLICENCE 700 1- Chakraborti Tapati Department of Biochemistry and Biophysics, University of Kalyani, 741235, Kalyani, West Bengal, India aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 400/1-2(2015-02-01), 107-123 0300-8177 400:1-2<107 2015 400 11010