title: 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.
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.
authors.affiliation: Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, Gong Ren Ti Yu Chang Nan Rd, Chaoyang District, Beijing, People's Republic of China.
authors.forename: Yan-Rui
authors.initials: YR
authors.lastname: Zhao
authors.affiliation: Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, Gong Ren Ti Yu Chang Nan Rd, Chaoyang District, Beijing, People's Republic of China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, Gong Ren Ti Yu Chang Nan Rd, Chaoyang District, Beijing, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, Gong Ren Ti Yu Chang Nan Rd, Chaoyang District, Beijing, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shan
authors.affiliation: Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, Gong Ren Ti Yu Chang Nan Rd, Chaoyang District, Beijing, People's Republic of China. doctorzyr@163.com.
authors.forename: Jun-Lin
authors.initials: JL
authors.lastname: Zhou
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology* / Q000503:physiopathology; D000818:Animals; D005121:Extremities / Q000098:blood supply*; D007378:Interleukins / Q000502:physiology; D007511:Ischemia / Q000150:complications* / Q000503:physiopathology; D053614:Janus Kinase 2 / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D051058:Oncogene Protein v-akt / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications* / Q000503:physiopathology; D050796:STAT3 Transcription Factor / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013458:Sulfur Dioxide / Q000378:metabolism*
chemical_list: D007378:Interleukins; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D013458:Sulfur Dioxide; D019869:Phosphatidylinositol 3-Kinases; C507927:Jak2 protein, rat; D053614:Janus Kinase 2; D051058:Oncogene Protein v-akt
keywords: Acute lung injury; Inhibitor; Ischemia/reperfusion; JAK2/STAT3; Na2SO3/NaHSO3; PI3K/Akt; Sulfur dioxide; p38 MAPK