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Targeting mitochondria with folic acid and vitamin B 12 ameliorates nicotine mediated islet cell dysfunction
Author(s) -
Bhattacharjee Ankita,
Prasad Shilpi Kumari,
Banerjee Oly,
Singh Siddhartha,
Banerjee Arnab,
Bose Ananya,
Pal Swagata,
Maji Bithin Kumar,
Mukherjee Sandip
Publication year - 2018
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.22586
Subject(s) - nicotine , mitochondrion , reactive oxygen species , endocrinology , chemistry , vitamin e , medicine , glutathione , lactate dehydrogenase , biochemistry , oxidative stress , biology , pharmacology , antioxidant , enzyme
Nicotine, one of the well‐known highly toxic components of cigarette smoke, causes a number of adverse health effects and diseases. Our previous study has shown that nicotine induces reactive oxygen species (ROS) in islet cell and disrupts islet cell mitochondrial membrane potential (ΔΨm). However, supplementation with folic acid and vitamin B 12 were found effective against nicotine induced changes in pancreatic islet cells. But the toxicological effects and underlying mechanisms of nicotine‐induced mitochondrial dysfunction is still unknown. In this study, nicotine exposure decreases mitochondrial enzymes (pyruvate dehydrogenase, alpha‐ketoglutarate dehydrogenase, aconitase, malate dehydrogenase) activities by increasing cytosolic Ca 2+ level which may contribute to increased mitochondrial ROS production by raising its flow to mitochondria. This in turn produces malondialdehyde and nitric oxide (NO) with a concomitant decrease in the activities of antioxidative enzymes and glutathione levels leading to loss of ΔΨm. Simultaneously, nicotine induces pancreatic islet cell apoptosis by modulating ΔΨm via increased cytosolic Ca 2+ level, altered Bcl‐2, Bax, cytochrome c, caspase‐9, PARP expressions which were prevented by the supplementation of folic acid and vitamin B 12 . In conclusion, nicotine alters islet cell mitochondrial redox status, apoptotic machinery, and enzymes to cause disruption in the ΔΨm and supplementation of folic acid and vitamin B 12 possibly blunted all these mitochondrial alterations. Therefore, this study may help to determine the pathophysiology of nicotine‐mediated islet cell mitochondrial dysfunction.