Oxidative stress reduces HDAC-2 activity and expression through the activation of PI3K-δ, leading to phosphorylation and ubiquitination of this epigenetic regulatory enzyme [62], peroxynitrite, which is increased in COPD lungs, also inactivates HDAC-2 by tyrosine nitration and ubiquitination [63]. Here, HDAC2 is linked to chronic obstructive pulmonary disease.