Blocking NAD+/CD38/cADPR/Ca2+ pathway in sepsis prevents organ damage

Peng, Qianyi; Ai, Meilin; Zhang, Lina; Zou, Yu; Ma, Xiaochun; Ai, Yuhang

doi:10.1016/j.jss.2015.11.029

Cited by 16 publications

(16 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The pathological scores for the liver and kidney were determined according to previous reports with minor modifications. 15,16 For the lung sections, the score was determined as the number of neutrophils in the alveolar space: 0 = no neutrophils, 1 = 1-10 in one field, 2 = 11-20 in one field, and 3 = >20 in one field. For the liver sections, the degree of inflammation, ballooning degeneration, and hepatic cord structure disruption was scored as follows: 0 = none, 1 = mild, 2 = moderate, and 3 = severe.…”

Section: Tissue Pathological Scorementioning

confidence: 99%

Prostaglandin F _2α receptor antagonist attenuates LPS‐induced systemic inflammatory response in mice

et al. 2020

View full text Add to dashboard Cite

Sepsis is a systemic immune response to infection. In patients with sepsis, many symptoms such as organ dysfunction, hypotension, hypothermia, or fever, increased level of leukocytes, and tachycardia are observed. 1 The hallmark pathological feature of sepsis is the infiltration of inflammatory leukocytes into multiple organs. Macrophages are the fast immune cells to phagocyte pathogens. These macrophages produce pro-inflammatory cytokines [eg, tumor necrosis factor (TNF)-α, interleukin (IL)-1, and IL-6] to induce the infiltration of other immune cells such as neutrophils. 2 Neutrophils also kill pathogens by producing oxidase-derived reactive oxygen species (ROS), cytotoxic granule components, antimicrobial peptides, and neutrophil extracellular traps (NETs). 3 Continuing or overproduction of pro-inflammatory cytokines, ROS, and NETs in macrophages and neutrophils caused tissue damages, and the incidence of severe sepsis and septic shock was increased. In

show abstract

Section: Tissue Pathological Scorementioning

confidence: 99%

Prostaglandin F _2α receptor antagonist attenuates LPS‐induced systemic inflammatory response in mice

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The CLP+ 8-Br-cADPR group was injected with 1 µmol/kg 8-Br-cADPR dissolved in normal saline solution through the tail vein immediately after CLP surgery. [ 22 ] Rats were killed after anesthesia, and the lungs were collected and frozen in liquid nitrogen or were perfused and fixed for histology studies.…”

Section: Ethodsmentioning

confidence: 99%

“…Intracellular NAD + levels were measured by an enzyme cycling method as described previously. [ 22 23 ] Briefly, lung tissues were pulverized into a powder in liquid nitrogen, resuspended in 100 mmol/L HCl, put on ice for 10 min, and then centrifuged at 12,000 × g . The acid-soluble fractions were neutralized with 100 mmol/L KOH.…”

Section: Ethodsmentioning

confidence: 99%

Blocking Cyclic Adenosine Diphosphate Ribose-mediated Calcium Overload Attenuates Sepsis-induced Acute Lung Injury in Rats

Peng

Zou

Zhang

et al. 2016

Chinese Medical Journal

Self Cite

View full text Add to dashboard Cite

Background:Acute lung injury (ALI) is a common complication of sepsis that is associated with high mortality. Intracellular Ca2+ overload plays an important role in the pathophysiology of sepsis-induced ALI, and cyclic adenosine diphosphate ribose (cADPR) is an important regulator of intracellular Ca2+ mobilization. The cluster of differentiation 38 (CD38)/cADPR pathway has been found to play roles in multiple inflammatory processes but its role in sepsis-induced ALI is still unknown. This study aimed to investigate whether the CD38/cADPR signaling pathway is activated in sepsis-induced ALI and whether blocking cADPR-mediated calcium overload attenuates ALI.Methods:Septic rat models were established by cecal ligation and puncture (CLP). Rats were divided into the sham group, the CLP group, and the CLP+ 8-bromo-cyclic adenosine diphosphate ribose (8-Br-cADPR) group. Nicotinamide adenine dinucleotide (NAD+), cADPR, CD38, and intracellular Ca2+ levels in the lung tissues were measured at 6, 12, 24, and 48 h after CLP surgery. Lung histologic injury, tumor necrosis factor (TNF)-α, malondialdehyde (MDA) levels, and superoxide dismutase (SOD) activities were measured.Results:NAD+, cADPR, CD38, and intracellular Ca2+ levels in the lungs of septic rats increased significantly at 24 h after CLP surgery. Treatment with 8-Br-cADPR, a specific inhibitor of cADPR, significantly reduced intracellular Ca2+ levels (P = 0.007), attenuated lung histological injury (P = 0.023), reduced TNF-α and MDA levels (P < 0.001 and P = 0.002, respectively) and recovered SOD activity (P = 0.031) in the lungs of septic rats.Conclusions:The CD38/cADPR pathway is activated in the lungs of septic rats, and blocking cADPR-mediated calcium overload with 8-Br-cADPR protects against sepsis-induced ALI.

show abstract

“…Another plausible explanation of lower NAD + levels in CIS-mediated renal damage is the up-regulation of ADP-ribosyl cyclase indicated by formation of cADPR in kidney tissue samples and in Vero cells. Data analysis also revealed further mobilization of calcium (high cytosolic calcium levels) upon CIS treatment or IRR exposure as a consequence of cADPR synthesis or extreme ROS formation [ 42 , 43 ]; the effect that was abolished by pretreatment with L-TH. Despite the anti-apoptotic effect of L-TH on normal Vero cells have been elucidated, the therapeutic potential targeting CIS anti-colorectal carcinoma (Caco-2) has not been disturbed upon L-TH pre-incubation.…”

Section: Discussionmentioning

confidence: 99%

L-thyroxine modifies nephrotoxicity by regulating the apoptotic pathway: The possible role of CD38/ADP-ribosyl cyclase-mediated calcium mobilization

et al. 2017

View full text Add to dashboard Cite

Thyroid hormones are well-established as a key regulator of many cellular metabolic pathways developed in various pathogeneses. Here, we dedicated the current work to investigate the role of thyroid hormone analogue (L-thyroxine, L-TH) in regulating the renal cytotoxicity using in vivo and in vitro models. Swiss mice were exposed to gamma radiation (IRR, 6Gy) or treated with cisplatin (CIS, 15 mg/kg, i.p.) for induction of nephrotoxicity. Remarkably, pretreatment with L-TH (1μg/kg) ameliorated the elevated kidney function biomarkers, oxidative stress and protected the renal tissue from the subsequent cellular damage. Likewise, L-TH inhibited the apoptotic cascade by down-regulating the extreme consumption of the cellular energy (ATP), the expression of caspase-3 and Bax, and the stimulation of cyclic ADP ribose (cADPR)/calcium mobilization. Moreover, incubation with L-TH (120nM/4h) significantly blocked the cytotoxicity of CIS on Vero cells and the depletion of NAD+ content as well as modified the ADP-ribose cyclase (CD38) enzymatic activity. High doses of L-TH (up to30 nM/4h) inversely increased the radiosensitivity of Vero cells towards IRR (up to 6Gy). On the other hand, L-TH did not interfere CIS-induced cytotoxicity of colorectal adenocarcinoma (Caco-2) cell line. In conclusion, pretreatment with L-TH could be a promising protective approach to the renal cellular damage induced during either CIS or IRR therapy by regulating the unbalanced oxidative status, the expression of pro-apoptotic biomarkers via modulation of cADPR mediated-calcium mobilization.

show abstract

Blocking NAD+/CD38/cADPR/Ca2+ pathway in sepsis prevents organ damage

Cited by 16 publications

References 46 publications

Prostaglandin F _2α receptor antagonist attenuates LPS‐induced systemic inflammatory response in mice

Prostaglandin F _2α receptor antagonist attenuates LPS‐induced systemic inflammatory response in mice

Blocking Cyclic Adenosine Diphosphate Ribose-mediated Calcium Overload Attenuates Sepsis-induced Acute Lung Injury in Rats

L-thyroxine modifies nephrotoxicity by regulating the apoptotic pathway: The possible role of CD38/ADP-ribosyl cyclase-mediated calcium mobilization

Contact Info

Product

Resources

About

Blocking NAD+/CD38/cADPR/Ca2+ pathway in sepsis prevents organ damage

Cited by 16 publications

References 46 publications

Prostaglandin F 2α receptor antagonist attenuates LPS‐induced systemic inflammatory response in mice

Prostaglandin F 2α receptor antagonist attenuates LPS‐induced systemic inflammatory response in mice

Blocking Cyclic Adenosine Diphosphate Ribose-mediated Calcium Overload Attenuates Sepsis-induced Acute Lung Injury in Rats

L-thyroxine modifies nephrotoxicity by regulating the apoptotic pathway: The possible role of CD38/ADP-ribosyl cyclase-mediated calcium mobilization

Contact Info

Product

Resources

About

Prostaglandin F _2α receptor antagonist attenuates LPS‐induced systemic inflammatory response in mice

Prostaglandin F _2α receptor antagonist attenuates LPS‐induced systemic inflammatory response in mice