Activation of human prorenin by lipidic constituents of the cell membrane.
Activation of semipurified human kidney prorenin was found to occur in vitro in presence of a mixture of lipids that mimics the composition of the inner human cell membrane. The lipid-dependent activation was indeed only partial (38 +/- 4%) when compared to that obtained by trypsin in liquid phase (100 micrograms/mL) used as a control of maximal activation (100%) under our experimental conditions (semipurified human kidney prorenin in presence of semipurified human plasma renin substrate at a concentration of 1400 ng/mL, at pH 7.2). The phenomenon was time-dependent up to 60 min whereas the angiotensin I generated after 120 min was virtually the same as that generated after 60 min thus indicating a possible reversible activation of human prorenin. We speculate that prorenin may be reversibly activated by contact with the lipidic portion of the cell membrane either inside or outside the cells thus allowing a limited angiotensin II-generating cascade at a local site initiated by prorenin independently from the presence of active renin.
Glorioso
N
N
Dipartimento di Medicina Interna, Università di Sassari, Italy.
Troffa
C
C
Tonolo
G
G
Manunta
P
P
Madeddu
P
P
Melis
M G
MG
Pazzola
A
A
Pala
F
F
Maioli
M
M
Mameli
P
P
D000803:Angiotensin I / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000502:physiology*; D012083:Renin / Q000378:metabolism*; D013997:Time Factors
D004792:Enzyme Precursors; D008055:Lipids; D000803:Angiotensin I; D012083:Renin