Cigarette smoke (CS) is an important source of morbidity and early mortality worldwide. Besides causing various life-threatening diseases, CS is also known to cause hypoxia. Chronic hypoxia would induce early aging and premature death. Continuation of smoking during pregnancy is a known risk for the unborn child. Although carbon monoxide (CO) is considered to be a cause of hypoxia, the effect of other component(s) of CS on hypoxia is not known. Here we show by immunoblots and mass spectra analyses that in smoker's blood -benzoquinone (-BQ) derived from CS forms covalent adducts with cysteine 93 residues in both the β chains of hemoglobin (Hb) producing Hb--BQ adducts. UV-vis spectra and CD spectra analyses show that upon complexation with -BQ the structure of Hb is altered. Compared to nonsmoker's Hb, the content of α-helix decreased significantly in smoker's Hb ( = 0.0224). -BQ also induces aggregation of smoker's Hb as demonstrated by SDS-PAGE, dynamic light scattering and atomic force microscopy. Alteration of Hb structure in smoker's blood is accompanied by reduced oxygen binding capacity. Our results provide the first proof that -BQ is a cause of hypoxia in smokers. We also show that although both -BQ and CO are responsible for causing hypoxia in smokers, exposure to CO further affects the function over and above that produced by Hb--BQ adduct.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5615826 | PMC |
http://dx.doi.org/10.1016/j.toxrep.2016.02.001 | DOI Listing |
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!