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

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• 作者：Yan-Rui Zhao ; Dong Wang ; Yang Liu ; Lei Shan…
• 关键词：Sulfur dioxide ; Acute lung injury ; Ischemia/reperfusion ; Na2SO3/NaHSO3 ; JAK2/STAT3 ; PI3K/Akt ; p38 MAPK ; Inhibitor
• 刊名：The Journal of Physiological Sciences
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：66
• 期：3
• 页码：229-239
• 全文大小：5,960 KB
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• 作者单位：Yan-Rui Zhao (1)
  Dong Wang (1)
  Yang Liu (1)
  Lei Shan (1)
  Jun-Lin Zhou (1)
  
  1. Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, Gong Ren Ti Yu Chang Nan Rd, Chaoyang District, Beijing, People’s Republic of China
  
• 刊物主题：Human Physiology; Neurosciences; Animal Biochemistry; Animal Physiology; Cell Physiology; Neurobiology;
• 出版者：Springer Japan
• ISSN：1880-6562

文摘

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.