Calmodulin Antagonist, W-7 Inhibits the Mitogen-induced Proliferation in Peripheral Human Lymphocytes, Reflecting Alterations Associated with Aging

O investigate whether calmodulin can be related to the mitogen-induced proliferation by phytohemagglutinin-P (PHA-P) in peripheral lymphocytes, we studied the effect of calmodulin antagonist, N-(6-aminohexyl)-5-chloro-l-naphthalenesulfonamide hydrochloride (W-7) , on the mitogenic reaction. Healty human adults both males and females, age range 40-68) were examined. Under the stimulation with the mitogen PHA-P, lymphocytes were incubated for 72 hrs at 37℃ , with W-7 of 0, 2.5, 5, 10, 25 and 50μM. The effects of W-7 were determined by the inhibition of DNA synthesis, measuring the incorporation of [3^H]thymidine ([3^H]dT), in the culture medium with and without W-7. In all of the 36 subjects, W-7 exhibited the inhibition of [3^H]dT incorporation. These findings suggest that W-7-inhibits the PHA-mitogenic reaction, and that calmodulin is related to the initiation of the mitogen-induced proliferation. Furthermore, for all subjects, a positive correlation (N=36, r=0.457, ρ<0.01) was found between the age and inhibition ratio with W-7 at 10μM. These findings suggest that the marked increase in inhibition ratio with W-7 serves as a useful marker, reflecting the alterations associated with aging.

カルモジュリン

W-7

リンパ球

PHA

加齢の指標