Carbon monoxide stimulates astrocytic mitochondrial biogenesis via L-type Ca 2+ channel-mediated PGC-1α/ERRα activation

Choi, Yoon Kyung; Park, Joon Ha; Baek, Yi Yong; Won, Moo Ho; Jeoung, Dooil; Lee, Hansoo; Ha, Kwon Soo; Kwon, Young Guen; Kim, Young Myeong

doi:10.1016/j.bbrc.2016.09.063

Cited by 41 publications

(46 citation statements)

References 28 publications

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“…Furthermore, transplantation of retinal glia enhanced the regeneration of DRG axons after root crush in adult rats [ 62 ]. Two recently released studies discovered that CO prevented neuronal cell death by targeting astrocytic metabolism through purinergic signaling and Ca2+-mediated PGC-1α/ERRα activation [ 63 , 64 ]. The exact mechanism by which the reactive GFAP-positive cells in our culture model promoted RGC to regenerate their axon remains to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotection and neuroregeneration of retinal ganglion cells after intravitreal carbon monoxide release

et al. 2017

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PurposeRetinal ischemia induces apoptosis leading to neurodegeneration and vision impairment. Carbon monoxide (CO) in gaseous form showed cell-protective and anti-inflammatory effects after retinal ischemia-reperfusion-injury (IRI). These effects were also demonstrated for the intravenously administered CO-releasing molecule (CORM) ALF-186. This article summarizes the results of intravitreally released CO to assess its suitability as a neuroprotective and neuroregenerative agent.MethodsWater-soluble CORM ALF-186 (25 μg), PBS, or inactivated ALF (iALF) (all 5 μl) were intravitreally applied into the left eyes of rats directly after retinal IRI for 1 h. Their right eyes remained unaffected and were used for comparison. Retinal tissue was harvested 24 h after intervention to analyze mRNA or protein expression of Caspase-3, pERK1/2, p38, HSP70/90, NF-kappaB, AIF-1 (allograft inflammatory factor), TNF-α, and GAP-43. Densities of fluorogold-prelabeled retinal ganglion cells (RGC) were examined in flat-mounted retinae seven days after IRI and were expressed as mean/mm2. The ability of RGC to regenerate their axon was evaluated two and seven days after IRI using retinal explants in laminin-1-coated cultures. Immunohistochemistry was used to analyze the different cell types growing out of the retinal explants.ResultsCompared to the RGC-density in the contralateral right eyes (2804±214 RGC/mm2; data are mean±SD), IRI+PBS injection resulted in a remarkable loss of RGC (1554±159 RGC/mm2), p<0.001. Intravitreally injected ALF-186 immediately after IRI provided RGC protection and reduced the extent of RGC-damage (IRI+PBS 1554±159 vs. IRI+ALF 2179±286, p<0.001). ALF-186 increased the IRI-mediated phosphorylation of MAP-kinase p38. Anti-apoptotic and anti-inflammatory effects were detectable as Caspase-3, NF-kappaB, TNF-α, and AIF-1 expression were significantly reduced after IRI+ALF in comparison to IRI+PBS or IRI+iALF. Gap-43 expression was significantly increased after IRI+ALF. iALF showed effects similar to PBS. The intrinsic regenerative potential of RGC-axons was induced to nearly identical levels after IRI and ALF or iALF-treatment under growth-permissive conditions, although RGC viability differed significantly in both groups. Intravitreal CO further increased the IRI-induced migration of GFAP-positive cells out of retinal explants and their transdifferentiation, which was detected by re-expression of beta-III tubulin and nestin.ConclusionIntravitreal CORM ALF-186 protected RGC after IRI and stimulated their axons to regenerate in vitro. ALF conveyed anti-apoptotic, anti-inflammatory, and growth-associated signaling after IRI. CO’s role in neuroregeneration and its effect on retinal glial cells needs further investigation.

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Section: Discussionmentioning

confidence: 99%

Neuroprotection and neuroregeneration of retinal ganglion cells after intravitreal carbon monoxide release

et al. 2017

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“…The CO-HO-1 axis increases angiogenesis by upregulating angiogenic stimulators such as interleukin (IL)-8, vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1 [10]. Moreover, the CO-HO-1 pathway increases ATP production through mitochondrial biogenesis [31,[39][40][41], possibly establishing environmental conditions for axonal growth [42]. In this review, we suggest that the CO-HO-1 pathway may affect (1) the intrinsic pathways of neuronal axon regeneration, (2) the expression of neurotrophic factors (i.e., brain-derived neurotrophic factor (BDNF), glial cell-line derived neurotrophic factor (GDNF) and ciliary neurotrophic factor (CNTF)) and (3) axonal regeneration through adult neurogenesis, angiogenesis and mitochondrial biogenesis after CNS injuries.…”

Section: Biological Signaling Of Co: Use Of Co Gas and Cormsmentioning

confidence: 99%

“…In CO/R conditioned astrocyte cells, Ca 2+ entry via L-type Ca 2+ channels can induce Ca 2+ -calmodulin kinase kinase β (CaMKKβ)-mediated AMPKα activation and these effects are initiated by CO and bilirubin [38]. CO/R stimulates the sequential AMPKα-SIRT1-PGC-1α axis in astrocytes, leading to enhanced ATP production and mitochondrial biogenesis [39]. Moreover, CO/R enhances circuits between HIF-1α and ERRα in astrocytes, leading to VEGF upregulation as well as mitochondrial biogenesis [40] (Figure 2).…”

Section: Mitochondria Functionmentioning

confidence: 99%

“…Transfer of astrocytic-derived mitochondria into neurons may enhance neuroplasticity and behavioral improvement [109]. In recent studies, astrocytic HO-1 induction increases the protein levels of two transcription factors, such as HIF-1α and ERRα, in a mouse model of ischemia/reperfusion injury [38][39][40]. Treatment of human astrocyte cells with CO/R enhances HIF-1α stabilization by eliciting the sequential activation of the sequential Ca 2+ -AMPKα-PGC-1α-ERRα axis [40].…”

Section: Strokementioning

confidence: 99%

“…Treatment of human astrocyte cells with CO/R enhances HIF-1α stabilization by eliciting the sequential activation of the sequential Ca 2+ -AMPKα-PGC-1α-ERRα axis [40]. This pathway results in increases in mitochondrial biogenesis and oxygen consumption, resulting in transient low oxygen levels that stabilizes the HIF-1α protein [38,39]. Activation of astrocytic HIF-1α in the CNS may contribute to mitochondrial biogenesis, neuroprotection and angiogenesis after ischemic injury [96,156].…”

Section: Strokementioning

confidence: 99%

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Regenerative Potential of Carbon Monoxide in Adult Neural Circuits of the Central Nervous System

Jung

Koh

Yoo

et al. 2020

IJMS

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Regeneration of adult neural circuits after an injury is limited in the central nervous system (CNS). Heme oxygenase (HO) is an enzyme that produces HO metabolites, such as carbon monoxide (CO), biliverdin and iron by heme degradation. CO may act as a biological signal transduction effector in CNS regeneration by stimulating neuronal intrinsic and extrinsic mechanisms as well as mitochondrial biogenesis. CO may give directions by which the injured neurovascular system switches into regeneration mode by stimulating endogenous neural stem cells and endothelial cells to produce neurons and vessels capable of replacing injured neurons and vessels in the CNS. The present review discusses the regenerative potential of CO in acute and chronic neuroinflammatory diseases of the CNS, such as stroke, traumatic brain injury, multiple sclerosis and Alzheimer’s disease and the role of signaling pathways and neurotrophic factors. CO-mediated facilitation of cellular communications may boost regeneration, consequently forming functional adult neural circuits in CNS injury.

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RETRACTED ARTICLE: Antioxidative effects of polypyrimidine tract-binding protein-associated splicing factor against pathological retinal angiogenesis through promotion of mitochondrial function

Dong

Lin

et al. 2021

J Mol Med

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Carbon monoxide stimulates astrocytic mitochondrial biogenesis via L-type Ca 2+ channel-mediated PGC-1α/ERRα activation

Cited by 41 publications

References 28 publications

Neuroprotection and neuroregeneration of retinal ganglion cells after intravitreal carbon monoxide release

Neuroprotection and neuroregeneration of retinal ganglion cells after intravitreal carbon monoxide release

Regenerative Potential of Carbon Monoxide in Adult Neural Circuits of the Central Nervous System

RETRACTED ARTICLE: Antioxidative effects of polypyrimidine tract-binding protein-associated splicing factor against pathological retinal angiogenesis through promotion of mitochondrial function

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