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

• Published in: The journal of physiological sciences Vol. 66; no. 3; pp. 229 - 239
• Main Authors: Zhao, Yan-Rui, Wang, Dong, Liu, Yang, Shan, Lei, Zhou, Jun-Lin
• Format: Journal Article
• Language: English
• Published: Japan Elsevier Inc 01.05.2016; Springer Japan
• Subjects: Acute lung injury; Acute Lung Injury - etiology; Acute Lung Injury - physiopathology; Animals; Extremities - blood supply; Inhibitor; Interleukins - physiology; Ischemia - complications; Ischemia - physiopathology; Ischemia/reperfusion; JAK2/STAT3; Janus Kinase 2 - physiology; Male; MAP Kinase Signaling System - physiology; Na2SO3/NaHSO3; Oncogene Protein v-akt - physiology; Original Paper; p38 MAPK; Phosphatidylinositol 3-Kinases - physiology; PI3K/Akt; Rats; Rats, Sprague-Dawley; Reperfusion Injury - complications; Reperfusion Injury - physiopathology; Signal Transduction - physiology; STAT3 Transcription Factor - physiology; Sulfur dioxide; Sulfur Dioxide - metabolism; Acute lung injury; Na2SO3/NaHSO3; JAK2/STAT3; Inhibitor; Ischemia/reperfusion; p38 MAPK; Sulfur dioxide; PI3K/Akt
• DOI: 10.1007/s12576-015-0418-z
• ISSN: 1880-6546; 1880-6562

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.