Carbon monoxide differentially modulates STAT1 and STAT3 and inhibits apoptosis via a phosphatidylinositol 3-kinase/Akt and p38 kinase-dependent STAT3 pathway during anoxia-reoxygenation injury
Authors: Peiying Shan
Patty J Lee
Jawed Alam
Xin-Yuan Fu
Xuchen Zhang
Journal: Journal of Biological Chemistry (2005)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Carbon monoxide; signaling mechanisms; endothelial cells; apoptosis; STAT1
Affiliations: Section of Pulmonary & Critical Care Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.

Abstract:  Carbon monoxide (CO), previously considered a toxic waste product of heme catabolism, is emerging as an important gaseous molecule. In addition to its important role in neurotransmission, exogenous CO protects against vascular injury, transplant rejection, and acute lung injury. However, little is known regarding the precise signaling mechanisms of CO. We have recently shown that CO attenuates endothelial cell apoptosis during anoxia-reoxygenation injury by activating MKK3/p38alpha mitogen-activated protein kinase (MAPK) pathways. Our current study is the first to demonstrate that CO can differentially modulate STAT1 and STAT3 activation and, specifically, that STAT3 activation by CO is responsible for the anti-apoptotic effect in endothelial cells. In addition, we show that the anti-apoptotic effects of CO depend upon both phosphatidylinositol 3-kinase/Akt and p38 MAPK signaling pathways in endothelial cells, whereas previous reports have implicated only the MKK3/p38 MAPK pathway. Using chemical inhibitors and dominant negative constructs, we show that CO enhances STAT3 activation via phosphatidylinositol 3-kinase/Akt and p38 MAPK pathways with subsequent attenuation of Fas expression and caspase 3 activity. These data highlight the anti-apoptotic signaling mechanisms of CO and, importantly, delineate potential therapeutic strategies to prevent ischemia-reperfusion or anoxia-reoxygenation injury in the vasculature. 

Retracted: No

PubPeer comments:
 In Figure 7, a micrograph has been duplicated and presented as something else (c vs d). ![file] , 
 Many thanks for the interest in novel bioactive bone substitutes. As reported, the significant progress has been made with the incorporation of strontium, which obviously stimulates the new bone formation. We do hope more audience can comment on it and further improve our findings. In Fig. 7, we found 6Sr and 9Sr showed more mineralization comparing with other groups at lower or higher Sr, but 6Sr showed best cell response. In that case, we checked the original images and found c and d were taken from the same sample of 6Sr with continuous imaging, but with wrong labeling in group d. That was because they were very close. So, it can be found the some portion of the images were the same, that was because they were from the same sample. It might be the mistake with the collection of pics with wrong labelling and also many difficult to be detected by eyes. I have to say the research work needs to be thoroughly checked before publication, and many thanks to point out this. We will contact with the editor and fix the image in fig 7d asap. We do hope the further collaboration can be made globally, in particular for osteoporotic application and commercialization. , 
 An extensive correction has been published: https: www.sciencedirect.com science article pii S2452199X20303303 , 
 From the correction:  3. After carefully re-examined the origin data, it was found that u201cWnt3Au201d was written into u201cWnt5Au201d mistakenly, and the authors deeply regretted the careless. As a matter of fact, u201cWnt5Au201d isn t included in the genes of Wnt u03b2-catenin signaling pathway (classical Wnt pathway). Therefore, all of the u201cWnt5Au201d was revised to u201cWnt3Au201d, including in Fig. 9a and b. Also, after carefully re-examined, it was found that u201cDKK1u201d was written into u201cDDK1u201d mistakenly in Fig 9b, and the authors deeply regretted the careless. Therefore, u201cDDK1u201d in Fig 9b was revised to u201cDKK1u201d. I am not so sure if it s that easy, to just change the text. The primer used for RT-PCR for Wnt5A, is actually specific for Wnt5A (Table 3). Also, this primer is specific for mouse and not human. The study was performed in human cells. Please note that also the primer sequence for RUNX2 in Table 3 is wrong (it is specific for OCN). ![file] ,