Oxidative calcium influx is mediated by plasma membrane cation-permeable ion channels. The transient receptor potential protein (TRP) and its homologs are cation channels with a tetramer secondary structure which senses diverse stimuli from the extracellular and intracellular Figure 6 Over-expression of endothelial ZO-1 attenuates PM-induced EC barrier disruption in vitro and pulmonary inflammation in vivo. (A) Human lung microvascular EC were grown to 60% confluence and treated with ZO-1 expression plasmid with X-fect reagent for 48 hr, and over-expression of ZO-1 protein was confirmed by Western blot. (B) The ECs were then challenged with PM (100 μg/ml), and changes in TER after 6 hr were measured with ECIS. *p < 0.05 compared to PM-challenged group. AJ mice were treated with ZO-1 expression plasmid with an ACE antibody-conjugated liposome delivery system (5 mg/kg) for 3 days, then challenged with PM (10 mg/kg). After 24 hr of PM exposure, (C) lung ZO-1 levels were analyzed with Western blot. Shown is one of the three repeated blots. BAL was collected and (D) protein content, (E) total white blood cell, and (F) IL-6 levels were measured. N = 4. *p < 0.05 compared to PM-challenged group. **p < 0.05 compared to control. environments [49] . Mammalian TRPs comprise six major subfamilies. TRPM2, a member of the TRP channel M2 subtype, is a calcium-permeable channel activated by intracellular messengers such as ADP-ribose [50] . Massive ROS burden induced by PM contributes to DNA oxidation and damage, which activates poly-ADP ribose polymerase (PARP) to initiate DNA repair mechanisms. PARP binds to single-stranded and double-stranded DNA breaks and catalyses the breakdown of NAD into nicotinamide and ADPribose, the intracellular agonist of TRPM2 [22, 51, 52] . Oxidative stress-mediated activation of the PARP pathway serves as the major source of free ADP-ribose production in endothelial cells [53] . Intracellular ADP-ribose activates TRPM2, allowing calcium ions to enter the cell, which in turn trigger numerous physiological and pathological processes.