cAMP elevating agents suppress secretory phospholipase A(2)-induced matrix metalloproteinase-2 activation |
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Authors: | Lee Chuhee Lee Jingu Choi Young-Ae Kang Shin-Sung Baek Suk-Hwan |
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Institution: | Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, Daegu 705-035, South Korea; Aging-Associated Vascular Disease Research Center, Daegu 705-035, South Korea. |
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Abstract: | Phospholipase A2 proteins are major regulators of the arachidonic acid cascade and are involved in various cellular responses. Previously, we reported that group IB PLA2 proteins stimulate MMP-2 activation and subsequent cell migration. Here, we describe a novel mechanism whereby sPLA2-induced proMMP-2 activation is regulated by intracellular cAMP in HT1080 cells, although sPLA2 itself had no effect on the regulation of cAMP levels. Exogenous dibutyryl cAMP (a cAMP analogue) strongly inhibited proMMP-2 activation, and cAMP elevating agents, namely, cholera toxin (a Gs activator) and forskolin (an adenylyl cyclase activator), abrogated basal and sPLA2-induced proMMP-2 activation. We also found that the down-regulation of TIMP-2 expression and extracellular signal-regulated kinase (ERK)1/2 activation by sPLA2 were blocked by increasing the intracellular cAMP level. Taken together, our data indicate that sPLA2-induced proMMP-2 activation is influenced by intracellular cAMP levels via the modulations of TIMP-2 expression and ERK1/2 activation. |
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Keywords: | sPLA2 MMP-2 cAMP TIMP-2 ERK1/2 |
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