Heme oxygenase-1–derived carbon monoxide enhances the host defense response to microbial sepsis in mice

Chung, Sung Min; Liu, Xiaoli; Macias, Alvaro A.; Baron, Rebecca M.; Perrella, Mark A.

doi:10.1172/jci32730

Cited by 281 publications

(288 citation statements)

References 46 publications

Supporting

Mentioning

277

Contrasting

Unclassified

Order By: Relevance

“…These include, severe sepsis [11,41,51], severe malaria [42], ischemia-reperfusion injury [2,14,31], rejection of transplanted organs [8], induction of immunological tolerance [61], autoimmune neuroinflammation [10], restenosis [4,37], myocardial infarction [27] and, as illustrated more recently, type 2 diabetes and obesity [23].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic efficacy of naringin on cyclosporine (A) induced nephrotoxicity in rats: Involvement of hemeoxygenase-1

Chandramohan

Parameswari

2013

Pharmacological Reports

View full text Add to dashboard Cite

Abstract:Background: Clinically, chronic nephrotoxicity may lead to renal functional impairment and progress to end stage renal failure. The renoprotective effect of a flavonoid naringin (NG) against cyclosporine A (CsA)-induced nephrotoxicity was investigated in this study. Methods: Nephrotoxicity was induced in male albino Wistar rats by injecting 25 mg/kg body weight of CsA for a period of 21 days. CsA-induced rats were also cotreated with 40 mg of NG/kg body weight, orally. Results: After the experimental period, the levels of lipid peroxides (TBARS) and hydroxyl radical (OH ) were found to be elevated, whereas the levels of SOD, catalase, glutathione, vitamin C, E and A were decreased in CsA-induced rats. NG co-treatment significantly decreased the levels of lipid peroxides and hydroxyl radicals and restored the levels of enzymic and non-enzymic antioxidants in renal tissues. Histological analysis revealed that CsA administration caused severe and widespread necrosis with dilatation of proximal tubules, vacuolization, tubular cell desquamation and intraluminal cast formation with massive infiltration of inflammatory cells. CsA-induced histopathological renal changes were minimal in animals which received NG treatment. The western blot and confocal microscopic expression of heme oxygenase-1 was restored by NG. In CsA-induced animals the expression was reduced compared to NG treated animals. Conclusions: The present study reveals that NG can act as effective renoprotective drug against CsA-induced toxicity.

show abstract

Section: Discussionmentioning

confidence: 99%

Therapeutic efficacy of naringin on cyclosporine (A) induced nephrotoxicity in rats: Involvement of hemeoxygenase-1

Chandramohan

Parameswari

2013

Pharmacological Reports

View full text Add to dashboard Cite

show abstract

“…CLP was performed as described 53 with minor modifications. Briefly, the mouse cecum was exposed through a 1.5-cm incision and the cecum was ligated with 4-0 silk without causing bowel obstruction and then perforated with a 22-gauge needle (Korea Vaccine, ND.SY1030-010) (1 hole injury).…”

Section: Animal Experimentsmentioning

confidence: 99%

SESN2/sestrin2 suppresses sepsis by inducing mitophagy and inhibiting NLRP3 activation in macrophages

et al. 2016

View full text Add to dashboard Cite

Proper regulation of mitophagy for mitochondrial homeostasis is important in various inflammatory diseases. However, the precise mechanisms by which mitophagy is activated to regulate inflammatory responses remain largely unknown. The NLRP3 (NLR family, pyrin domain containing 3) inflammasome serves as a platform that triggers the activation of CASP1 (caspase 1) and secretion of proinflammatory cytokines. Here, we demonstrate that SESN2 (sestrin 2), known as stress-inducible protein, suppresses prolonged NLRP3 inflammasome activation by clearance of damaged mitochondria through inducing mitophagy in macrophages. SESN2 plays a dual role in inducing mitophagy in response to inflammasome activation. First, SESN2 induces "mitochondrial priming" by marking mitochondria for recognition by the autophagic machinery. For mitochondrial preparing, SESN2 facilitates the perinuclear-clustering of mitochondria by mediating aggregation of SQSTM1 (sequestosome 1) and its binding to lysine 63 (Lys63)-linked ubiquitins on the mitochondrial surface. Second, SESN2 activates the specific autophagic machinery for degradation of primed mitochondria via an increase of ULK1 (unc-51 like kinase 1) protein levels. Moreover, increased SESN2 expression by extended LPS (lipopolysaccharide) stimulation is mediated by NOS2 (nitric oxide synthase 2, inducible)-mediated NO (nitric oxide) in macrophages. Thus, Sesn2-deficient mice displayed defective mitophagy, which resulted in hyperactivation of inflammasomes and increased mortality in 2 different sepsis models. Our findings define a unique regulatory mechanism of mitophagy activation for immunological homeostasis that protects the host from sepsis.

show abstract

“…For instance, HO-1-derived carbon monoxide enhances the host defense response to microbial sepsis in mice. 73 A recent study demonstrated that high-mobility group box 1 contributes to lethality of endotoxemia in HO-1-deficient mice. 74 A significant reduction of high-mobility group box 1 was noted after administration of carbon monoxide and biliverdin, products of the HO-1 enzymatic pathway.…”

Section: Therapeutic Options For the Present And Futurementioning

confidence: 99%

Sepsis and Acute Kidney Injury

Zarjou

Agarwal

2011

Journal of the American Society of Nephrology

452

363

View full text Add to dashboard Cite

Heme oxygenase-1–derived carbon monoxide enhances the host defense response to microbial sepsis in mice

Cited by 281 publications

References 46 publications

Therapeutic efficacy of naringin on cyclosporine (A) induced nephrotoxicity in rats: Involvement of hemeoxygenase-1

Therapeutic efficacy of naringin on cyclosporine (A) induced nephrotoxicity in rats: Involvement of hemeoxygenase-1

SESN2/sestrin2 suppresses sepsis by inducing mitophagy and inhibiting NLRP3 activation in macrophages

Sepsis and Acute Kidney Injury

Contact Info

Product

Resources

About