New Study Uncovers How Nicotine Triggers Heart Cell Damage

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PASADENA, Calif. — June 6, 2024 — A new study led by Dr. Nicole H. Purcell, Senior Scientist at Huntington Medical Research Institutes (HMRI), and Dr. Khaja Shameem Mohammed Abdul reveals a key molecular pathway by which nicotine exposure causes oxidative stress and cell death in the heart.

Published in the Journal of Molecular and Cellular Cardiology, the paper — “Increased PHLPP1 Expression Through ERK–4E-BP1 Signaling Axis Drives Nicotine-Induced Oxidative Stress–Related Damage of Cardiomyocytes” — identifies a novel mechanism linking nicotine exposure to mitochondrial dysfunction and cardiomyocyte injury.

The research team — Khaja Shameem Mohammed Abdul, Kimin Han, Alyssa B. Guerrero, Cekia N. Wilson, Amogh Kulkarni, and Nicole H. Purcell — demonstrated that nicotine exposure:

  • Increases expression of the enzyme PHLPP1 (Pleckstrin Homology Domain Leucine-Rich Repeat Protein Phosphatase 1) in adolescent rodent hearts and cultured cardiomyocytes.

  • Activates the ERK/4E-BP1 signaling pathway, which in turn drives PHLPP1 protein synthesis.

  • Elevates NADPH oxidase 4 (NOX4) levels and reactive oxygen species (ROS) production, leading to oxidative stress and cardiomyocyte apoptosis.

  • Causes mitochondrial dysfunction that depends directly on PHLPP1 activity.

Importantly, inhibiting ERK activation or protein synthesis prevented the nicotine-induced increase in PHLPP1, confirming that this pathway is central to the mechanism of injury.

“This work provides new insight into how nicotine — whether from traditional or electronic cigarettes — damages heart cells at the molecular level,” said Dr. Purcell. “By identifying PHLPP1 as a critical mediator, we open new possibilities for therapeutic intervention.”

The findings deepen understanding of nicotine’s cellular toxicity and align with HMRI’s broader research focus on cardiovascular injury and recovery mechanisms.

Full article: Journal of Molecular and Cellular Cardiology, June 2024