Aspirin-triggered resolvin D1 down-regulates inflammatory responses and protects against endotoxin-induced acute kidney injury

Chen, Jiao; Shetty, Sreerama; Zhang, Ping; Gao, Rong; Hu, Yuxin; Wang, Shuxia; Li, Zhenyu; Fu, Jing

doi:10.1016/j.taap.2014.03.017

Cited by 73 publications

(60 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Site-directed mutagenesis has further revealed that HK2 is phosphorylated by Akt on threonine 473 within an Akt consensus sequence in cardiomyocytes in vitro (44). We examined signaling changes in the renal cortex that might precede HK activation and noted increased activation of Akt as early as 1 h after LPS administration, which is consistent with other reports (11,31). Inhibition of Akt by MK-2206 attenuated increases in HK activity following LPS exposure.…”

Section: F441supporting

confidence: 87%

Renal cortical hexokinase and pentose phosphate pathway activation through the EGFR/Akt signaling pathway in endotoxin-induced acute kidney injury

Smith

Stallons

Schnellmann

2014

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

Smith JA, Stallons LJ, Schnellmann RG. Renal cortical hexokinase and pentose phosphate pathway activation through the EGFR/ Akt signaling pathway in endotoxin-induced acute kidney injury. Am J Physiol Renal Physiol 307: F435-F444, 2014. First published July 2, 2014; doi:10.1152/ajprenal.00271.2014.-While disruption of energy production is an important contributor to renal injury, metabolic alterations in sepsis-induced AKI remain understudied. We assessed changes in renal cortical glycolytic metabolism in a mouse model of sepsis-induced AKI. A specific and rapid increase in hexokinase (HK) activity (ϳ2-fold) was observed 3 h after LPS exposure and maintained up to 18 h, in association with a decline in renal function as measured by blood urea nitrogen (BUN). LPS-induced HK activation occurred independently of HK isoform expression or mitochondrial localization. No other changes in glycolytic enzymes were observed. LPS-mediated HK activation was not sufficient to increase glycolytic flux as indicated by reduced or unchanged pyruvate and lactate levels in the renal cortex. LPS-induced HK activation was associated with increased glucose-6-phosphate dehydrogenase activity but not glycogen production. Mechanistically, LPS-induced HK activation was attenuated by pharmacological inhibitors of the EGF receptor (EGFR) and Akt, indicating that EGFR/phosphatidylinositol 3-kinase/Akt signaling is responsible. Our findings reveal LPS rapidly increases renal cortical HK activity in an EGFR-and Akt-dependent manner and that HK activation is linked to increased pentose phosphate pathway activity.lipopolysaccharide; acute kidney injury; hexokinase; EGFR; pentose phosphate pathway ACUTE KIDNEY INJURY (AKI) is defined as an abrupt decline in renal function which occurs over a period of hours to days (7). A number of stimuli may lead to the development of AKI, including sepsis, ischemia-reperfusion (I/R) injury, trauma, or exposure to nephrotoxic agents. Among the leading causes of AKI, sepsis is thought to be the most common contributor (ϳ50% of all cases) in the intensive care unit (ICU) setting (64). Despite increased understanding of the pathophysiology underlying AKI, mortality from the disease remains near 40% and has not changed over several decades (27,60,65). AKI in the setting of sepsis increases this mortality by almost twofold (48, 65). Unfortunately, currently available treatments for sepsis-induced AKI include supportive care and renal replacement therapy. A better understanding of the mechanisms leading to renal damage as well as recovery in septic AKI is essential for development of therapeutic strategies to improve outcomes in this disease.The pathophysiology of sepsis-induced AKI is widely recognized as multifactorial, involving microvascular, immunological, and tubular components that contribute to renal dysfunction. The microvascular component is characterized by reduced capillary flow, leading to local areas of hypoperfusion (29,30,66). Infiltration of both macrophages and neutrophils also exposes the septic ki...

show abstract

Section: F441supporting

confidence: 87%

Renal cortical hexokinase and pentose phosphate pathway activation through the EGFR/Akt signaling pathway in endotoxin-induced acute kidney injury

Smith

Stallons

Schnellmann

2014

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

show abstract

“…Reduced infiltration of neutrophils, lower expression of adhesion molecules and less activation of NF-κB has been reported [105]. …”

Section: Molecules Involved In Resolution Of Inflammationmentioning

confidence: 99%

Pro-Resolving Molecules—New Approaches to Treat Sepsis?

Buechler

Pohl

Aslanidis

2017

IJMS

View full text Add to dashboard Cite

Inflammation is a complex response of the body to exogenous and endogenous insults. Chronic and systemic diseases are attributed to uncontrolled inflammation. Molecules involved in the initiation of inflammation are very well studied while pathways regulating its resolution are insufficiently investigated. Approaches to down-modulate mediators relevant for the onset and duration of inflammation are successful in some chronic diseases, while all of them have failed in sepsis patients. Inflammation and immune suppression characterize sepsis, indicating that anti-inflammatory strategies alone are inappropriate for its therapy. Heme oxygenase 1 is a sensitive marker for oxidative stress and is upregulated in inflammation. Carbon monoxide, which is produced by this enzyme, initiates multiple anti-inflammatory and pro-resolving activities with higher production of omega-3 fatty acid-derived lipid metabolites being one of its protective actions. Pro-resolving lipids named maresins, resolvins and protectins originate from the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid while lipoxins are derived from arachidonic acid. These endogenously produced lipids do not simply limit inflammation but actively contribute to its resolution, and thus provide an opportunity to combat chronic inflammatory diseases and eventually sepsis.

show abstract

“…Moreover, animal studies confirm an aspirin-induced resolvin-mediated attenuation of AKI during endotoxemia. 64 Like other DAMPs, histones (nuclear gene-regulating proteins) are released by necroptotic cells, activate the immune system and promote sepsis-induced organ injury. 65 Activated protein C, which degrades extracellular histones, was a previously approved therapy for sepsis but was removed from the market owing to lack of efficacy in a large RCT.…”

Section: Future Therapiesmentioning

confidence: 99%