Oxidative Stress Associated with Aging Activates Protein Kinase Ce, Leading to Cilia Slowing

Details

• Personal Author:
  Bailey KL ; Katafiasz DM ; Kharbanda KK ; Sisson JH ; Wyatt TA
• Description:
  Older people are four times more likely to develop pneumonia than younger people. As we age, many components of pulmonary innate immunity are impaired, including slowing of mucociliary clearance. Ciliary beat frequency (CBF) is a major determinant of mucociliary clearance, and it slows as we age. We hypothesized that CBF is slowed in aging because of increased oxidative stress, which activates PKCe signaling. We pharmacologically inhibited PKCe in ex vivo mouse models of aging. We measured a slowing of CBF with aging that was reversed with inhibition using the novel PKC inhibitor, Ro-31-8220, as well as the PKCe inhibitor, PKCe141. Inhibition of PKCe using siRNA in mouse trachea also returned CBF to normal. In addition, antioxidants decrease PKCe activity and speed cilia. We also aged wild-type and PKCe KO mice and measured CBF. The PKCe KO mice were spared from the CBF slowing of aging. Using human airway epithelial cells from younger and older donors at air-liquid interface (ALI), we inhibited PKCe with siRNA. We measured a slowing of CBF with aging that was reversed with siRNA inhibition of PKCe. In addition, we measured bead clearance speeds in human ALI, which demonstrated a decrease in bead velocity with aging and a return to baseline after inhibition of PKCe. In summary, in human and mouse models, aging is associated with increased oxidant stress, which activates PKCe and slows CBF. [Description provided by NIOSH]
• Subjects:
  Aging Animals Lung Occupational Health Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Aging; Lung Function; Lung Cells; Oxidative Stress; Cell Signaling; Proteins; Animal Studies; Respiratory Infections; Physiological Function; Author Keywords: Aging; Airway Epithelial Cells; Ciliary Beat Frequency; Elderly; Mucociliary Clearance; PKCe Pneumonia; SiRNA
• DOI:
  https://doi.org/10.1152/ajplung.00033.2018
• ISSN:
  1040-0605
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  Nebraska ; OSHA Region 7
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  315
• Issue:
  5
• NIOSHTIC Number:
  nn:20065196
• Citation:
  Am J Physiol Lung Cell Mol Physiol 2018 Nov; 315(5):L882-L890
• Contact Point Address:
  K. L. Bailey, 985910 Nebraska Medical Center, Univ. of Nebraska Medical Center, Omaha, NE 68198-5910
• Email:
  kbailey@unmc.edu
• Federal Fiscal Year:
  2019
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of Nebraska Medical Center - Omaha
• Peer Reviewed:
  True
• Start Date:
  20110901
• Source Full Name:
  American Journal of Physiology: Lung Cellular and Molecular Physiology
• End Date:
  20270831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:97b466e408318a59a3bbb5a3fe151ea60f3edf064cf1e26ee6b24ab076c6975d2e54960b3f295fcfc702d2fd4774f4ce8be19f106961961ef4fdb50ec4f33528
• Download URL:
  https://stacks.cdc.gov/view/cdc/248960/cdc_248960_DS1.pdf
• File Type:
  [PDF - 819.46 KB ]