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The p38/MAPK pathway regulates microtubule polymerization through phosphorylation of MAP4 and Op18 in hypoxic cells

Jiong-Yu Hu1, Zhi-Gang Chu, Jian Han

  • 1State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Burn Research, Southwest Hospital, The Third Military Medical University, 400038, Chongqing, People's Republic of China.

Cellular and Molecular Life Sciences : CMLS
|November 17, 2009
PubMed

Insights

Hypoxia disrupts microtubules by activating the p38/MAPK pathway, altering phosphorylation of MAP4 and Op18, which reduces cell viability. This study reveals key molecular mechanisms behind hypoxic cell damage.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Physiology

Background:

  • Hypoxia rapidly disrupts microtubules in cells, but early dynamic changes remain unclear.
  • Understanding microtubule dynamics under hypoxia is crucial for cell survival research.

Purpose of the Study:

  • To investigate the early molecular mechanisms of microtubule disruption during hypoxia.
  • To identify signaling pathways and proteins involved in hypoxia-induced cell damage.

Main Methods:

  • Studied microtubule-associated protein 4 (MAP4) and oncoprotein 18/stathmin (Op18) phosphorylation.
  • Assessed p38/MAPK activity and its downstream effects.
  • Utilized immunoprecipitation and pharmacological inhibitors (SB203580) and genetic manipulation (MKK6(Glu) overexpression).

Main Results:

  • Hypoxia increased MAP4 phosphorylation and decreased Op18 phosphorylation without changing protein levels.
  • p38/MAPK activation correlated with these phosphorylation changes and induced microtubule disruption.
  • Inhibition of p38/MAPK improved hypoxic cell viability, while MKK6(Glu) overexpression decreased it.

Conclusions:

  • Hypoxia triggers microtubule depolymerization and reduced cell viability through p38/MAPK pathway activation.
  • Altered phosphorylation of MAP4 and Op18 are key downstream events in this process.

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