Cigarette smoke induces metabolic reprogramming in lung cells

Uncategorized
  1. Hitendra S. Solanki1,2,
  2. Niraj Babu1,3,
  3. Ankit Jain1,2,
  4. Mohd Younis Bhat1,4,
  5. Vinuth N. Puttamallesh1,4,
  6. Jayshree Advani1,3,
  7. Remya Raja1,
  8. Kiran K. Mangalaparthi1,4,
  9. Mahesh M. Kumar5,
  10. T. S. Keshava Prasad1,6,7,
  11. Premendu Prakash Mathur2,
  12. David Sidransky8,
  13. Harsha Gowda1,7*,
  14. Aditi Chatterjee1,7*

Authors Affiliation(s)

  • 1Institute of Bioinformatics, International Tech Park, Bangalore 560066, INDIA
  • 2School of Biotechnology, KIIT University, Bhubaneswar, Odisha 751024, INDIA
  • 3Manipal University, Madhav Nagar, Manipal 576104, INDIA
  • 4Amrita School of Biotechnology, Amrita University, Kollam 690525, INDIA
  • 5Department of Neuro-Virology, National Institute of Mental Health and Neurosciences, Bangalore 560029, INDIA
  • 6NIMHANS-IOB Proteomics and Bioinformatics Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bangalore 560029, INDIA
  • 7YU-IOB Center for Systems Biology and Molecular Medicine, Yenepoya University, Mangalore 575018, INDIA
  • 8Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine; Baltimore, MD 21231, USA

Can J Biotech, Volume 1, Special Issue-Supplement, Page 281, DOI: https://doi.org/10.24870/cjb.2017-a265

Presenting author: hitendra08@gmail.com; *Corresponding authors: aditi@ibioinformatics.org, harsha@ibioinformatics.org

Abstract

Cigarette smoking remains the leading cause of non-small cell lung carcinoma. Studies involving acute exposure of smoke on lung cells revealed induction of pre- cancerous state in lung cells. Recently few studies have reported the chronic effect of cigarette smoke in inducing cellular transformation. Yet no systemic study has been performed to understand the molecular alterations in lung cells due to cigarette smoke. Hence it is both important and necessary to study the chronic effect of cigarette smoke in a temporal setting to understand the molecular alterations. In this study, we carried out TMT based proteomic profiling of lung cells which were exposed to cigarette smoke condensate (CSC) for upto 12 months. We identified 2621 proteins in total, of which 145, 114, 87, 169 and 671 proteins were differentially expressed (p<0.05, 1.5 fold) in 2nd, 4th, 6th, 8th and 12th month respectively.Pathway analysis revealed enrichment of xenobiotic metabolism signaling for the first 8 months of smoke treatment, whereas continued exposure of smoke for 12 months revealed mitochondrial reprogramming in cells which includes dysregulation of oxidative phosphorylation machinery leading to enhanced reactive oxygen species and higher expression of enzymes involved in tricarboxylic acid cycle (TCA). In addition, chronic exposure of smoke led to overexpression of enzymes involved in glutamine metabolism, fatty acid degradation and lactate synthesis. This could possibly explain the availability of alternative source of carbon in TCA cycle apart from glycolytic pyruvate. Our data indicates that chronic exposure to cigarette smoke induces metabolic transformation in cells to support growth and survival.