Nicotine proteome effects tissue-specific alterations – ezine – raid 5 data recovery

Many consumers who vape believe that it is harmless. Cigarettes are known to cause many diseases including cancer, bronchitis, emphysema, heart disease and stroke, among others, but e-cigarettes do not contain tobacco so are “safe”. While it is true that the vapour from e-cigarettes does not contain the 7000 chemicals that are found in tobacco smoke, there is increasing evidence that they are not as healthy as some might think.

This is of growing concern to health authorities worldwide given the rapid rise in the numbers of people vaping. The World Health Organization has estimated that 35 million people used e-cigarettes in 2016, a rise from 7 million in 2011, and predicts 55 million users by 2021. While there has been a multitude of research studies into the effects of smoking, as well as secondhand and thirdhand smoke, the equivalent research on e-cigarette smoking is much sparser, partly due to the shorter time that they have been available.

It is possible that related diseases have yet to reveal themselves.

The key ingredient in e-cigarettes is nicotine, which is toxic to developing foetuses, can damage adolescent brain development and is a suspected carcinogen. It is supplemented by flavourings and the carriers propylene glycol and glycerin which produce toxic aldehydes upon heating. In addition, a recent study published in 2017 demonstrated that e-cigarettes have detrimental effects on the airways and could initiate respiratory diseases.

These warning signs could be the tip of the iceberg and it is generally agreed that more research should be carried out on the effects of vaping and of inhaling nicotine. One new study carried out in the US has looked at the effects of orally ingested nicotine on the proteins in various organs in mice. Joao Paulo, Steven Gygi, Mark Jedrychowski, Edward Chouchani and Lawrence Kazak from Harvard Medical School and the Dana-Farber Cancer Institute in Boston published their findings in Proteomics, revealing "the vast extent of exposure across murine tissue". Tandem mass tagging

The nicotine was administered in drinking water to five mice while five others were given normal water. After 21 days, tissue was dissected from seven organs: the brain, heart, kidney, liver, lung, pancreas and spleen. The proteins from each organ were extracted and digested with Lys-C then trypsin to produce mixtures of peptides.

In order to compare the peptide abundances across the treated and control animals, the mixtures from each tissue were treated with ten tandem mass tagging reagents which were then pooled 1:1 across all of the samples. After further offline fractionation, the peptides were analysed by liquid chromatography-tandem mass spectrometry and the ion counts for all peptide spectrum matches in the reference database were used to determine the relative amounts of each protein.

A refined sample processing protocol used lower amounts of starting material than those typically required for proteomics experiments and permitted fast offline centrifugation-based fractionation. This made it far easier to compare the proteins in the different tissues, all 70 samples being fractionated within one hour. Localised actions of nicotine in different tissues

More than 138,000 individual peptides were quantified in all seven tissues, leading to the identification of 11,516 proteins. The number of proteins in each tissue ranged from 5325 in the pancreas to 7839 in spleen, approaching the numbers that have been reported in other studies that used far more starting material.

Within a particular tissue, the proteins with altered abundances caused by nicotine exposure numbered 7,27, 34, 35, 36, 105 and 126 for pancreas, brain, heart, kidney, liver, lung and spleen, respectively, but the totals did not correlate with total proteins measured in each type. Of these, 11 were significantly altered in more than one tissue. The implicated pathways included lipid metabolism, iron metabolism, amino acid degradation, calcium signalling, and fatty acid metabolism.

"These proteins may serve as a basis to dissect further the role of nicotine in pathway modulation and to target specific mechanisms that lead to or are a consequence of the observed protein alterations", the team declared. "They may be key candidates for further targeted experiments and validation with orthogonal techniques such as Western blotting, immunofluorescence or mass spectrometry based MS2."

Clearly, the effects of nicotine across the human body are widespread, although they are local rather than global. The chemical was taken orally in these experiments so the results need to be confirmed by inhalation, to mimic more closely the effects of electronic cigarettes and provide a better understanding of nicotine damage.