A team of scientists conducting a study to examine COPD development at the cellular level demonstrated that free radicals could reach the endoplasmic reticulum and alter its function. Anna Blumental-Perry, PhD, and colleagues aimed to better understand the mechanisms of a fairly new scientific concept: the smoke induced collapse of protein homeostasis and its contribution to age-dependent onset of COPD. Knowing that upon inhalation of cigarette smoke (CS), the free radicals in it can reach the interior of lung cells where they react with a wide variety of cell proteins and affect their functions, the scientists formed the hypothesis that CS-free radicals can interfere with proper folding of the proteins within the cell, reports Science Daily.
The findings showed that free radicals, which are small, unstable molecules present in CS, can reach the endoplasmic reticulum, a cellular organelle that is critical in manufacturing and transporting fats, steroids, hormones and various proteins, and alter its function by oxidizing and damaging its most abundant and crucial to protein folding chaperone, Protein Disulfide Isomerase (PDI), according to Science Daily. Determining that PDI is a vital factor in the development of COPD, the research team identified how cells adapt to the presence of less functional PDI; specifically, increasing the levels of it through a mechanism at the protein synthesis level as opposed to the level of gene transcription.
The Science Daily report indicates that since adaptation wears off with age, the researchers have now identified one of the first clues to age-dependency in COPD onset.
“Understanding the mechanisms of the collapse of protein homeostasis in COPD allows us to focus on maintaining functional levels of PDI. This could improve outcomes for the many patients with COPD as well as potentially giving us clues to improve health with aging.” said Blumental-Perry. “We discovered that PDI is a critical new factor in the pathogenesis of COPD, and that protein collapse in COPD is age dependent and unpredictable. Based on these fascinating findings, we plan to conduct future research targeting failed adaptive systems in an effort to maintain functional levels of PDI, and prevent it from acquisitions of ‘bad’ functions — discoveries that could ultimately help us to identify new therapeutic approaches for COPD.”
Photo Credit: Case Western Reserve University School of Medicine
Source: Science Daily