Ischemia/Reperfusion-Induced Injury of Forebrain Mitochondria and Protection by Ascorbate

Sciamanna, Michele A.; Lee, C.P.

doi:10.1006/abbi.1993.1414

Cited by 89 publications

(38 citation statements)

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“…VCP-Na does not directly act as a cofactor for hydroxylation of proline and lysine residues in procollagen molecules, but it is dephosphorylated on the cell membrane and incorporated as vitamin C. 14,15) The presence of VCP-IS-2Na in cultured normal human fibroblasts could not be confirmed, but instead, the intercellular amount of vitamin C was observed to increase. Therefore, to exhibit vitamin C activity, VCP-IS-2Na needs to be hydrolyzed before membrane transport.…”

Section: Discussionmentioning

confidence: 89%

“…For example, vitamin C increases enzyme activity [9][10][11] ; acts as an inducer of the collagen pathway 12) ; and scavenges free radicals as an antioxidant during oxidant stress. 13,14) An essential function of vitamin C is to act as a cofactor for the hydroxylation of proline and lysine residues in collagen, a major protein component of the body. Vitamin C also increases the transcription rate of procollagen genes and stabilizes procollagen mRNA.…”

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confidence: 99%

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Effect of a Novel Ascorbic Derivative, Disodium Isostearyl 2-O-L-Ascorbyl Phosphate on Human Dermal Fibroblasts: Increased Collagen Synthesis and Inhibition of MMP-1

Shibayama

Hisama²,

Matsuda³

et al. 2008

Biological & Pharmaceutical Bulletin

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Normal cells, including fibroblasts, show density-dependent growth and form monolayers in culture. 1) This is quite different from cell behavior in vivo, where the cells are multilayered and surrounded by extracellular matrix (ECM) components, such as collagen and proteoglycan produced by the cells themselves. The active role of ECM in cell attachment, proliferation 2) and differentiation 3) has recently been recognized. Artificial collagen gels 4) and insoluble ECM 5) obtained from various tissues have been used in studies on cell growth and differentiation. Type I collagen is a major structural protein and is found in large quantities in various parts of the body, especially in the skin, bones, teeth and tendons. A decrease in the production of type I collagen, or that of defective molecules, induces organ deformity or dysfunction and retards embryo and fetus development in extreme cases. [6][7][8] On the other hand, aberrant accumulation of type I collagen in tissues and organs results in organ fibrosis, such as in progressive systemic sclerosis (scleroderma) of the skin, liver fibrosis and pulmonary fibrosis, and also occasionally endangers the life of affected individuals. 7,8) L-Ascorbic acid (vitamin C) is known to be a neutral bioactive agent, and its multifarious activities in many biological systems have been reported. For example, vitamin C increases enzyme activity [9][10][11] ; acts as an inducer of the collagen pathway 12) ; and scavenges free radicals as an antioxidant during oxidant stress. 13,14) An essential function of vitamin C is to act as a cofactor for the hydroxylation of proline and lysine residues in collagen, a major protein component of the body. Vitamin C also increases the transcription rate of procollagen genes and stabilizes procollagen mRNA. 15,16) Its ability to cure scurvy is possibly due to stimulation of collagen synthesis in connective tissues.17) However, vitamin C is unstable in aqueous solutions, even under normal culture conditions at neutral pH and 37°C. To solve this problem, a number of stable derivatives, including L-ascorbic acid 2-sulfate and L-ascorbic acid 2-phosphate (VCP-Na), have been developed. 18,19) VCP-Na shows antiscorbutic activity in guinea pigs, 20,21) and has a stimulatory effect on collagen synthesis in cultured human skin fibroblasts, 22,23) while L-ascorbic acid 2-sulfate does not show these effects. 24)We have recently synthesized a novel lipophilic alkyl vitamin C derivative, sodium isostearyl 2-O-L-ascorbyl phosphate (VCP-IS-Na), which is characterized by its high stability in various aqueous solutions, throughout a wide range of pH values, and its non-reducibility. 25) We have also demonstrated that VCP-IS-Na is superior to VCP-Na with regard to enzymatic hydrolysis by tissue esterase and/or phosphatase to give vitamin C. These findings indicate that vitamin C, released from VCP-IS-Na by enzymatic hydrolysis, exhibits these biological activities.Structurally, the difference between the existing vitamin C derivative VCP-Na and the novel vitamin ...

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Section: Discussionmentioning

confidence: 89%

mentioning

confidence: 99%

Effect of a Novel Ascorbic Derivative, Disodium Isostearyl 2-O-L-Ascorbyl Phosphate on Human Dermal Fibroblasts: Increased Collagen Synthesis and Inhibition of MMP-1

Shibayama

Hisama²,

Matsuda³

et al. 2008

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

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“…Both complex 1 and 2 maximum respiration have been shown to drop by approximately 50% following a moderate unilateral CCI in SD rats (Opii et al, 2007). Significant changes in both NAD-linked and succinate-driven respiration have also been reported following ischemic=reperfusion injury (Sciamanna et al, 1992;Sciamanna and Lee, 1993), as well as spinal cord contusion injury ( Jin et al, 2004).…”

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confidence: 99%

Early Mitochondrial Dysfunction after Cortical Contusion Injury

Gilmer

Roberts

Joy³

et al. 2009

Journal of Neurotrauma

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Following traumatic brain injury, mitochondria sustain structural and functional impairment, which contributes to secondary damage that can continue for days after the initial injury. The present study investigated mitochondrial bioenergetic changes in the rat neocortex at 1 and 3 h after mild, moderate, and severe injuries. Brains from young adult Sprague-Dawley rats were harvested from the injured and contralateral cortex to assess possible changes in mitochondrial respiration abilities following a unilateral cortical contusion injury. Differential centrifugation was used to isolate synaptic and extrasynaptic mitochondria from cortical tissue. Bioenergetics was assessed using a Clark-type electrode and results were graphed as a function of injury severity and time postinjury. Respiration was significantly affected by all injury severity levels compared to uninjured tissue. Complex 1-and complex 2-driven respirations were affected proportionally to the severity of the injury, indicating that damage to mitochondria may occur on a gradient. Total oxygen utilization, respiratory control ratio, ATP production, and maximal respiration capabilities were all significantly decreased in the injured cortex at both 1 and 3 h post-trauma. Although mitochondria displayed bioenergetic deficits at 1 h following injury, damage was not exacerbated by 3 h. This study stresses the importance of early therapeutic intervention and suggests a window of approximately 1-3 h before greater dysfunction occurs.

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“…Mitochondria from hippocampus/liver of 9-11 day old rat pups and hippocampal organotypic slices were isolated according to the procedure described previously (Sciamanna and Lee, 1993). In brief, rat pups were anesthetized using 5% isoflurane (70 % N 2 O -30 % O 2 ).…”

Section: Isolation Of Mitochondriamentioning

confidence: 99%

ɛPKC phosphorylates the mitochondrial K+ATP channel during induction of ischemic preconditioning in the rat hippocampus

et al. 2007

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Neuroprotection against cerebral ischemia conferred by ischemic preconditioning (IPC) requires translocation of epsilon protein kinase C (εPKC). A major goal in our laboratory is to define the cellular targets by which εPKC confers protection. We tested the hypothesis that εPKC targets the mitochondrial channel ( ) after IPC. Our results demonstrated a rapid translocation of εPKC to rat hippocampal mitochondria after IPC. Because in other tissues εPKC targets channels, but its presence in brain mitochondria is controversial, we determined the presence of the channel-specific subunits (Kir6.1 and Kir6.2) in mitochondria isolated from rat hippocampus. Next, we determined whether channels play a role in the IPC induction. In hippocampal organotypic slice cultures, IPC and lethal ischemia were induced by oxygen-glucose deprivation. Subsequent cell death in the CA1 region was quantified using propidium iodide staining. Treatment with the channel openers diazoxide or pinacidil 48 h prior to lethal ischemia protected hippocampal CA1 neurons, mimicking the induction of neuroprotection conferred by either IPC or εPKC agonist-induced preconditioning. Blockade of channels using 5-hydroxydecanoic acid abolished the neuroprotection due to either IPC or εPKC preconditioning. Both ischemic andεPKC agonist-mediated preconditioning resulted in phosphorylation of the channel subunit Kir6.2. After IPC, selective inhibition of εPKC activation prevented Kir6.2 phosphorylation, consistent with Kir6.2 as a phosphorylation target of εPKC or its downstream effectors. Our results support the hypothesis that the brain channel is an important target of IPC and the signal transduction pathways initiated by εPKC.

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Ischemia/Reperfusion-Induced Injury of Forebrain Mitochondria and Protection by Ascorbate

Cited by 89 publications

References 0 publications

Effect of a Novel Ascorbic Derivative, Disodium Isostearyl 2-O-L-Ascorbyl Phosphate on Human Dermal Fibroblasts: Increased Collagen Synthesis and Inhibition of MMP-1

Effect of a Novel Ascorbic Derivative, Disodium Isostearyl 2-O-L-Ascorbyl Phosphate on Human Dermal Fibroblasts: Increased Collagen Synthesis and Inhibition of MMP-1

Early Mitochondrial Dysfunction after Cortical Contusion Injury

ɛPKC phosphorylates the mitochondrial K+ATP channel during induction of ischemic preconditioning in the rat hippocampus

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