Identification of signaling pathways involved in aberrant production of adipokines in adipocytes undergoing oxidative stress.
OBJECTIVE
In obesity, oxidative stress is responsible for the aberrant production of adipokines such as adiponectin, plasminogen activator inhibitor (PAI)-1 and interleukin-6 (IL-6), which is causally associated with obesity-related inflammation, insulin resistance and cardiovascular disease. However, the signaling transduction pathways participating in adipokine dysregulation induced by oxidative stress are largely unknown. Thus, the aim of the present study was to identify possible involved signaling pathways.


METHODS
3T3-L1 cells were differentiated into adipocytes and underwent oxidative stress by exposure to extraneous H(2)O(2). Quantitative PCR and immunoassays were performed to determine mRNA and protein levels of adipokines (adiponectin, PAI-1 and IL-6), respectively. Possible signaling pathways involved were high-throughout identified by Bioplex phosphoprotein assays and subsequently confirmed by inhibition of the targeted protein kinases such as Akt, ERK1/2, JAK/STAT, JNK, and p70 S6K, respectively.


RESULTS
H(2)O(2) markedly suppressed adiponectin mRNA expression as well as protein secretion; however, it enhanced PAI-1 and IL-6 production in mature adipocytes. Akt,JAK/STAT and ERK1/2 participated in the H(2)O(2)-induced increase of PAI-1 and IL-6 expression, whereas adiponectin expression was reduced by H(2)O(2) via Akt and JAK/STAT.


CONCLUSIONS
Akt and JAK/STAT are congenerous pathways through which oxidative stress downregulates adiponectin and upregulates PAI-1 and IL-6 expression. ERK1/2 participates not in H(2)O(2)-induced decrease of adiponectin expression, but in the increase of PAI-1 and IL-6.
Chen
Baoying
B
Department of Radiology, Tangdu Hospital, Fourth Military Medical University, Shaanxi, China.
Wei
Jingguo
J
Wang
Wei
W
Cui
Guangbin
G
Zhao
Yufeng
Y
Zhu
Xiaoxing
X
Zhu
Miaozhang
M
Guo
Wei
W
Yu
Jun
J
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D052242:Adiponectin / Q000096:biosynthesis*; D000818:Animals; D002460:Cell Line; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015850:Interleukin-6 / Q000819:agonists / Q000378:metabolism*; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011494:Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D058258:Serpin E2; D015843:Serpins / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
D052242:Adiponectin; D015850:Interleukin-6; D012333:RNA, Messenger; D058258:Serpin E2; C511869:Serpine2 protein, mouse; D015843:Serpins; D006861:Hydrogen Peroxide; D011494:Protein Kinases