Smoking related diseases: the central role of monoamine oxidase

Abstract

Smoking is a major risk factor of morbidity and mortality. It is well established that monoamine oxidase (MAO) activity is decreased in smokers. Serotonin (5-HT), a major substrate for MAO that circulates as a reserve pool stored in platelets, is a marker of platelet activation. We recently reported that smoking durably modifies the platelet 5-HT/MAO system by inducing a demethylation of the MAO gene promoter resulting in high MAO protein concentration persisting more than ten years after quitting smoking. The present data enlarges the results to another MAO substrate, norepinephrine (NE), further confirming the central role of MAO in tobacco use-induced diseases. Thus, MAO could be a readily accessible and helpful marker in the risk evaluation of smoking-related diseases, from cardiovascular and pulmonary diseases to depression, anxiety and cancer. The present review implements the new finding of epigenetic regulation of MAO and suggests that smoking-induced MAO demethylation can be considered as a hallmark of smoking-related cancers similarly to other aberrant DNA methylations.

Keywords: cancer; cardiovascular; depression; epigenetic; monoamine oxidase; norepinephrine; platelets; serotonin; smoking.

Figure 1

Platelet MAO in smokers (44 S), non smokers (34 NS) and former smokers (37 FS). Left: MAO activity (nmoles.mg protein⁻¹h⁻¹) Right: MAO amount (pmoles.mg protein⁻¹). **P < 0.001, ***P < 0.00001.

Figure 2

Norepinephrine (NE, left) and its metabolite DHPG (right) in the plasma from non smokers (white bars), former smokers (FS dotted bars), and smokers (S hatched bars) **P < 0.001; Differences between FS and S were not significant (P > 0.05) for NE and the same applies between NS and S for DHPG. NE and DHPG were determined by HPLC with electrochemical detection as previously described [8].

Figure 3

Correlation between platelet MAO amount and duration of smoking. A: in the whole population (smokers S + former smokers FS + non smokers NS: n = 108, r = 0.25, P < 0.01) and B: in smokers (S) above the cut-off value (n = 18, r = 0.77, P < 0.01).

Figure 4

Methylation of the 22 CpG sites of the MAOB promoter in PBMC from non smokers (4 NS, white bars), former smokers (4 FS, dotted bars) and smokers (5 S, hatched bars). The differences between NS and FS or S are significant at all sites (0.0001 < P < 0.02) except at sites 19–20.