Cellular and Molecular Life Sciences

, Volume 67, Issue 2, pp 321–333 | Cite as

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

  • Jiong-Yu Hu
  • Zhi-Gang Chu
  • Jian Han
  • Yong-ming Dang
  • Hong Yan
  • Qiong Zhang
  • Guang-ping Liang
  • Yue-Sheng Huang
Research Article

Abstract

In both cardiomyocytes and HeLa cells, hypoxia (1% O2) quickly leads to microtubule disruption, but little is known about how microtubule dynamics change during the early stages of hypoxia. We demonstrate that microtubule associated protein 4 (MAP4) phosphorylation increases while oncoprotein 18/stathmin (Op18) phosphorylation decreases after hypoxia, but their protein levels do not change. p38/MAPK activity increases quickly after hypoxia concomitant with MAP4 phosphorylation, and the activated p38/MAPK signaling leads to MAP4 phosphorylation and to Op18 dephosphorylation, both of which induce microtubule disruption. We confirmed the interaction between phospho-p38 and MAP4 using immunoprecipitation and found that SB203580, a p38/MAPK inhibitor, increases and MKK6(Glu) overexpression decreases hypoxic cell viability. Our results demonstrate that hypoxia induces microtubule depolymerization and decreased cell viability via the activation of the p38/MAPK signaling pathway and changes the phosphorylation levels of its downstream effectors, MAP4 and Op18.

Keywords

Cardiomyocyte HeLa cells Hypoxia Mitogen-activated protein kinase Microtubule associated protein Oncoprotein 18 Phosphorylation Cell culture 

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Copyright information

© Birkhäuser Verlag, Basel/Switzerland 2009

Authors and Affiliations

  • Jiong-Yu Hu
    • 1
  • Zhi-Gang Chu
    • 1
  • Jian Han
    • 2
  • Yong-ming Dang
    • 1
  • Hong Yan
    • 1
  • Qiong Zhang
    • 1
  • Guang-ping Liang
    • 1
  • Yue-Sheng Huang
    • 1
  1. 1.State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Burn Research, Southwest HospitalThe Third Military Medical UniversityChongqingPeople’s Republic of China
  2. 2.Department of Gynecology and Obstetrics, Daping HospitalThe Third Military Medical UniversityChongqingPeople’s Republic of China

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