Repercussion of isocyanates exposure on different cellular proteins in human pulmonary arterial endothelial cells

Abstract

The endothelium is the thin interior surface of blood vessels normally involved in many aspects of vascular biology; including vasoconstriction, vasodilatation, and angiogenesis can be injured by physical or chemical stress, particularly by the drugs and other environmental toxins.  Although, isocyanates have drawn significant attention in the recent past as they react with DNA to produce toxicogenomic insults due to high degree of reactivity and low molecular weight having functional group–N=C=O. Moreover, patho-physiological implications resulting from occupational and accidental exposures of these compounds are yet too elusive. On this premise, a strenuous effort was made to assess the cellular response of methyl isocyanate on cultured human pulmonary arterial endothelial cells (HPAE-26). Study was conducted in different time intervals to evaluate cellular response after exposure to isocyanates using N-succinimidyl N-methylcarbamate, a surrogate chemical substitute to methyl isocyanate (MIC). The role of different cell cycle regulatory proteins: cyclin A and E & cdk2; cell cycle inhibitory proteins: p53, p21& GADD45; DNA damage responsive proteins; ATM, ATR & γH2AX and repair proteins: Mre11, Nbs1 & Rad50 were evaluated through immuno-blotting. Our results demonstrate that isocyanates induced toxicity involved in vascular damage of endothelial cells with subsequent perturb expression of different tumor suppressor and repair proteins concurrently higher expression of Cdk2 and cyclins unveiled the progression of oncogenesis in the cells in-vitro.