Matrix metalloproteinase activity in transformed cells exposed to an antioxidant

Abstract

We showed that antioxidant N acetylcysteine (NAC, 2-10 mM) rapidly (in 2 h) and completely deactivated the activity of matrix metalloproteinases (MMPs) (MMP 2 and MMP 9 gelatinases and MMP 1 and MMP 8 collagenases) secreted by transformed 3T3 SV40 mouse fibroblasts into the medium. The same MMP inhibition took place in the cell free medium conditioned by HT 1080 fibroblasts. This suggests that the direct chemical interaction between NAC and MMP resulted in the loss of MMP activity. In addition to this inhibitory effect, NAC decreased MMP 1 and MMP 9 (but not MMP 2) production in the cell medium. However, the level of MMP 1 and MMP 9 inhibitors (TIMP 1) remained normal, indicating a shift in the balance between the enzyme and inhibitor. The correlation between MMP 2 and the tissue enzyme inhibitor TIMP 2 level was similar in control and NAC treated cells. Moreover, reorganization of collagen type I at the cell surface was observed. Taken together, our results suggest that NAC exposure results in extracellular matrix remodeling and a change in cellular functions.

<p>Evidence for a Beneficial Effect of Oral N-acetylcysteine on Functional Outcomes and Inflammatory Biomarkers in Patients with Acute Ischemic Stroke</p>

“…Given that activation of MMPs is dependent on the modification of the cysteine residue and reaction of ROS with thiol groups can activate these protolithic proteins, 79 it is thought NAC with abundant cysteine residues in its structures may have inhibitory effects on MMP-9 production and activation. 80,81 Taken together, this evidence explains NAC at least in theory via multiple mechanisms of action can exert protective effects on brain tissue during ischemic attacks. Our data also support that early use of NAC in stroke pationts is able to improve the clinical outcomes of these patients.…”