The Journal of Physiological Sciences

, Volume 66, Issue 3, pp 229–239 | Cite as

The PI3K/Akt, p38MAPK, and JAK2/STAT3 signaling pathways mediate the protection of SO2 against acute lung injury induced by limb ischemia/reperfusion in rats

  • Yan-Rui Zhao
  • Dong Wang
  • Yang Liu
  • Lei Shan
  • Jun-Lin Zhou
Original Paper

Abstract

Sulfur dioxide (SO2) is naturally synthesized by glutamate–oxaloacetate transaminase (GOT) from l-cysteine in mammalian cells. We found that SO2 may have a protective effect on acute lung injury (ALI) induced by limb ischemia/reperfusion (I/R) in rats. The PI3K/Akt, p38MAPK, and JAK2/STAT3 pathways are crucial in cell signaling transduction. The present study aims to verify the role of SO2 on limb I/R-induced ALI, and investigate whether PI3K/Akt, p38MAPK, and JAK2/STAT3 pathways were involved, as well as the relationship among the three pathways; we used specific inhibitors (LY294002, SB03580, and Stattic) to block them, respectively. The experimental methods of Western, ELISA, TUNEL, etc., were used to test the results. In the I/R group, the parameters of lung injury (MDA, MPO, TUNEL, cytokines) increased significantly, but the administration of Na2SO3/NaHSO3 attenuated the damage in the lung. The Western results showed that the rat’s lung exist expression of P-STAT3, P-AKT, and P-p38 proteins. After I/R, P-STAT3, P-Akt, and P-p38 proteins expression all increased. After using Na2SO3/NaHSO3, P-Akt, and P-p38 proteins expression increased, but P-STAT3 protein expression decreased. We also found a strange phenomenon; compared to the I/R + SO2 group, the administration of stattic, P-p38 protein expression showed no change, but P-Akt protein expression increased (p < 0.05). In conclusion, SO2 has a protective effect on rats with limb I/R-induced ALI. The JAK2/STAT3, PI3K/Akt, and p38MAPK pathways are likely all involved in the process, and the JAK2/STAT3 pathway may have an impact on the P13K/Akt pathway.

Keywords

Sulfur dioxide Acute lung injury Ischemia/reperfusion Na2SO3/NaHSO3 JAK2/STAT3 PI3K/Akt p38 MAPK Inhibitor 

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Copyright information

© The Physiological Society of Japan and Springer Japan 2015

Authors and Affiliations

  • Yan-Rui Zhao
    • 1
  • Dong Wang
    • 1
  • Yang Liu
    • 1
  • Lei Shan
    • 1
  • Jun-Lin Zhou
    • 1
  1. 1.Department of OrthopedicsBeijing Chaoyang Hospital, Capital Medical UniversityBeijingPeople’s Republic of China

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