NPD1 rapidly targets mitochondria-mediated apoptosis after acute injection protecting brain against ischemic injury

Zirpoli, Hylde; Sosunov, Sergey A.; Niatsetskaya, Zoya; Mayurasakorn, Korapat; Kollareth, Denny Joseph Manual; Serhan, Charles N.; Ten, Vadim S.; Deckelbaum, Richard J.

doi:10.1016/j.expneurol.2020.113495

Cited by 18 publications

(11 citation statements)

References 60 publications

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“…Dietary supplementation with fish oil for MCMV infection promoted mitochondrial biosynthesis in the liver cells of male C57BL/6 mice [ 44 ]. Both RvD1 and MCTR1 have been reported to improve mitochondrial biogenesis and function induced by multiple adverse factors, such as inflammation or high sugar levels [ 45 – 47 ].…”

Section: Discussionmentioning

confidence: 99%

Docosahexaenoic acid supplementation represses the early immune response against murine cytomegalovirus but enhances NK cell effector function

Wang

et al. 2022

BMC Immunol

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Background Docosahexaenoic acid (DHA) supplementation is beneficial for several chronic diseases; however, its effect on immune regulation is still debated. Given the prevalence of cytomegalovirus (CMV) infection and because natural killer (NK) cells are a component of innate immunity critical for controlling CMV infection, the current study explored the effect of a DHA-enriched diet on susceptibility to murine (M) CMV infection and the NK cell effector response to MCMV infection. Results Male C57BL/6 mice fed a control or DHA-enriched diet for 3 weeks were infected with MCMV and sacrificed at the indicated time points postinfection. Compared with control mice, DHA-fed mice had higher liver and spleen viral loads at day 7 postinfection, but final MCMV clearance was not affected. The total numbers of NK cells and their terminal mature cell subset (KLRG1+ and Ly49H+ NK cells) were reduced compared with those in control mice at day 7 postinfection but not day 21. DHA feeding resulted in higher IFN-γ and granzyme B expression in splenic NK cells at day 7 postinfection. A mechanistic analysis showed that the splenic NK cells of DHA-fed mice had enhanced glucose uptake, increased CD71 and CD98 expression, and higher mitochondrial mass than control mice. In addition, DHA-fed mice showed reductions in the total numbers and activation levels of CD4+ and CD8+ T cells. Conclusions These results suggest that DHA supplementation represses the early response to CMV infection but preserves NK cell effector functions by improving mitochondrial activity, which may play critical roles in subsequent MCMV clearance.

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Section: Discussionmentioning

confidence: 99%

Docosahexaenoic acid supplementation represses the early immune response against murine cytomegalovirus but enhances NK cell effector function

Wang

et al. 2022

BMC Immunol

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“…NPD1 may also work on mitochondria-related cell death pathways, which play a major role in ischemic brain injury. Following NPD1 acute intraperitoneal injection in mice, ischemic core expansion was prevented by about 40%; brain mitochondria showed a preserved membrane structure, together with a reduction of mitochondrial BAX translocation and activation [ 56 ]. NPD1 administration has also been demonstrated to promote neurogenesis and angiogenesis, BBB integrity, penumbra protection and subsequent long-term neurobehavioral recovery after experimental ischemic stroke [ 57 ].…”

Section: Specialized Pro-resolving Mediators and Potential Applicatio...mentioning

confidence: 99%

Specialized Pro-Resolving Mediators in Neuroinflammation: Overview of Studies and Perspectives of Clinical Applications

et al. 2022

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Specialized pro-resolving mediators (SPMs) are lipid mediators derived from poly-unsaturated fatty acids (PUFAs) which have been demonstrated to have an important role in the inflammation environment, preventing an overreaction of the organism and promoting the resolution of inflammation. Our purpose was to point out the current evidence for specialized pro-resolving mediators, focusing on their role in neuroinflammation and in major neurological diseases.

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“…In addition, NPD1 remains one of our most prominently detected mediators increased by LPS in our sCVOs cultures. This small pro-resolving lipid mediator (SPM) has multiple beneficial effects during brain inflammatory insults such as ischemic or traumatic brain injury [ 88 ] via preservation of mitochondrial membrane structure [ 89 ] or blockage of neuronal apoptosis and antioxidative effects [ 90 ]. However, caution needs to be taken as this mediator is hard to distinguish from its isomer protectin DX [ 91 ].…”

Section: Discussionmentioning

confidence: 99%

Norepinephrine Inhibits Lipopolysaccharide-Stimulated TNF-α but Not Oxylipin Induction in n-3/n-6 PUFA-Enriched Cultures of Circumventricular Organs

Pflieger

Wolf

Feldotto

et al. 2022

IJMS

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Sensory circumventricular organs (sCVOs) are pivotal brain structures involved in immune-to-brain communication with a leaky blood–brain barrier that detect circulating mediators such as lipopolysaccharide (LPS). Here, we aimed to investigate the potential of sCVOs to produce n-3 and n-6 oxylipins after LPS-stimulation. Moreover, we investigated if norepinephrine (NE) co-treatment can alter cytokine- and oxylipin-release. Thus, we stimulated rat primary neuroglial sCVO cultures under n-3- or n-6-enriched conditions with LPS or saline combined with NE or vehicle. Supernatants were assessed for cytokines by bioassays and oxylipins by HPLC-MS/MS. Expression of signaling pathways and enzymes were analyzed by RT-PCR. Tumor necrosis factor (TNF)α bioactivity and signaling, IL-10 expression, and cyclooxygenase (COX)2 were increased, epoxide hydroxylase (Ephx)2 was reduced, and lipoxygenase 15-(LOX) was not changed by LPS stimulation. Moreover, LPS induced increased levels of several n-6-derived oxylipins, including the COX-2 metabolite 15d-prostaglandin-J2 or the Ephx2 metabolite 14,15-DHET. For n-3-derived oxylipins, some were down- and some were upregulated, including 15-LOX-derived neuroprotectin D1 and 18-HEPE, known for their anti-inflammatory potential. While the LPS-induced increase in TNFα levels was significantly reduced by NE, oxylipins were not significantly altered by NE or changes in TNFα levels. In conclusion, LPS-induced oxylipins may play an important functional role in sCVOs for immune-to-brain communication.

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NPD1 rapidly targets mitochondria-mediated apoptosis after acute injection protecting brain against ischemic injury

Cited by 18 publications

References 60 publications

Docosahexaenoic acid supplementation represses the early immune response against murine cytomegalovirus but enhances NK cell effector function

Docosahexaenoic acid supplementation represses the early immune response against murine cytomegalovirus but enhances NK cell effector function

Specialized Pro-Resolving Mediators in Neuroinflammation: Overview of Studies and Perspectives of Clinical Applications

Norepinephrine Inhibits Lipopolysaccharide-Stimulated TNF-α but Not Oxylipin Induction in n-3/n-6 PUFA-Enriched Cultures of Circumventricular Organs

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