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. Author manuscript; available in PMC: 2011 Dec 31.
Published in final edited form as: Respir Physiol Neurobiol. 2010 Sep 8;174(3):299–306. doi: 10.1016/j.resp.2010.08.019

Fig. 3. Model of redox-dependent induction of senescence associated MMP-1.

Fig. 3

Our data suggests that age associated MMP-1 expression is redox-sensitive. The redox-dependence is initially due to the activation of c-Jun N-terminal kinase pathway. Previous results have also shown that the activation of JNK pathway involves activation of upstream MAPKK, MKK-4 and MKK-7. Our lab has shown that MKK-4 is similarly regulated in an age- and redox-dependent manner. Furthermore, with age there is decrease in total levels of MKP-1 which may implicate a process of “oxidative inactivation”. Use of kinase specific pharmacological and molecular inhibitor indicate that other MAP kinases such as Erk, p38 and PI-3-Kinase may also participate in oxidant-dependent regulation of MMP-1 transcription. To conclude, JNK is one of the key mediators of redox dependent MMP-1 induction and the senescence-dependent MMP-1 induction is a complex signaling process dependent on ROS regulating a number of distinct signaling networks that converge to drive MMP-1 expression. Dashed lines indicate sites of redox regulation.