Kinase activity, heat shock protein 27 phosphorylation, and lung epithelial cell glutathione

Robert Jackson, Rolando Garcia-Rojas

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The 27-kDa heat shock protein (Hps27) is phosphorylated in a way that appears to regulate antioxidant defenses by mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2), a component of the p38MAPK pathway. To investigate the role of Hsp27 in cellular resistance to oxidant stress, lung cells (A549) were incubated with MAPK inhibitors to investigate the pathway's role in antioxidant defense. Cells were harvested for measurement of reduced gluthathione and glutathione disulfide (GSH and GSSH); or, exposed to 2,3-dimethoxy-1,4-napthoquinone (DMNQ). Inhibition of MAPK with SB203580 decreased total cellular glutathione (mean ± SE): Vehicle, 150 ± 20 μM; SB203580, 57 ± 10* (*P <.01). Inhibition of MAPK tripled [GSSG]/[GSH]: Vehicle, 0.29 ± 0.09; SB203580, 1.06 ± 0.43* (*P >.05; n = 6 per group). Hsp27 protein content did not change significantly after MAPK inhibition: Vehicle 2.20 ± 0.24 ng/mg protein; SB203580, 2.03 ± 0.34 (P >.05). Transfection of epithelial cells with wild-type (pcDNA-HA-Hsp27) or phosphomimic (pcDNA-HA-Hsp27-S3D) vector increased Hsp27 protein, which significantly protected cells from oxidant stress. Inhibition of the MAPK system, including p38MAPK, results in cellular oxidant stress. Hsp27, which is phosphorylated by MK2 in the MAPK pathway, protects epithelial cells from oxidant stress.

Original languageEnglish
Pages (from-to)245-262
Number of pages18
JournalExperimental Lung Research
Volume34
Issue number5
DOIs
StatePublished - Jun 1 2008

Fingerprint

HSP27 Heat-Shock Proteins
Phosphorylation
Mitogen-Activated Protein Kinases
Glutathione
Phosphotransferases
Epithelial Cells
Oxidants
Lung
Antioxidants
Proteins
Glutathione Disulfide
Protein Kinase Inhibitors
Heat-Shock Proteins
Protein Kinases
Transfection
MAP-kinase-activated kinase 2
SB 203580

Keywords

  • Glutathione
  • Heat shock protein
  • Hypoxia
  • Kinases
  • Reactive oxygen species

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Kinase activity, heat shock protein 27 phosphorylation, and lung epithelial cell glutathione. / Jackson, Robert; Garcia-Rojas, Rolando.

In: Experimental Lung Research, Vol. 34, No. 5, 01.06.2008, p. 245-262.

Research output: Contribution to journalArticle

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