ArticleCell death & disease2014
Selective inhibition of protein kinase C β2 attenuates the adaptor P66 Shc-mediated intestinal ischemia-reperfusion injury.
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- Non-Ser36 phosphorylated p66Shc inhibits TRPC-dependent and TRPC-independent calcium influx in vascular smooth muscle cells.Biochemical and biophysical research communications · 2025Article
- Exploring the Gut-Mitochondrial Axis: p66Shc Adapter Protein and Its Implications for Metabolic Disorders.International journal of molecular sciences · 2024Review
- Advancements in the study of acute lung injury resulting from intestinal ischemia/reperfusion.Frontiers in medicine · 2024Review
- Protective Effect of Oxygen and Isoflurane in Rodent Model of Intestinal Ischemia-Reperfusion Injury.International journal of molecular sciences · 2023Article
- Cellular Signal Transduction Pathways Involved in Acute Lung Injury Induced by Intestinal Ischemia-Reperfusion.Oxidative medicine and cellular longevity · 2021Review
- Oxidative Stress in Intestinal Ischemia-Reperfusion.Frontiers in medicine · 2021Review
- The Inhibition of Protein Kinase C β Contributes to the Pathogenesis of Preeclampsia by Activating Autophagy.EBioMedicine · 2020Article
- circ-PRKCB acts as a ceRNA to regulate p66Shc-mediated oxidative stress in intestinal ischemia/reperfusion.Theranostics · 2020Article
- Diurnal oscillations of endogenous HNature cell biology · 2019Article
- Carvedilol alleviates diabetic cardiomyopathy in diabetic rats.Experimental and therapeutic medicine · 2019Article
- Epicatechin Gallate Protects HBMVECs from Ischemia/Reperfusion Injury through Ameliorating Apoptosis and Autophagy and Promoting Neovascularization.Oxidative medicine and cellular longevity · 2019Article
- PKCβII-induced upregulation of PGP9.5 and VEGF in postoperative persistent pain in rats.Journal of pain research · 2018Article
- MicroRNA-378 protects against intestinal ischemia/reperfusion injury via a mechanism involving the inhibition of intestinal mucosal cell apoptosis.Cell death & disease · 2017Article
- PKCζ phosphorylates TRAF2 to protect against intestinal ischemia-reperfusion-induced injury.Cell death & disease · 2017Article
- Protein kinase C beta II upregulates intercellular adhesion molecule-1 via mitochondrial activation in cultured endothelial cells.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2017Article
- MicroRNA-682-mediated downregulation of PTEN in intestinal epithelial cells ameliorates intestinal ischemia-reperfusion injury.Cell death & disease · 2016Article
- SIRTUIN 1 ACTIVATOR SRT1720 PROTECTS AGAINST ORGAN INJURY INDUCED BY INTESTINAL ISCHEMIA-REPERFUSION.Shock (Augusta, Ga.) · 2016Article
- PKCδ promotes high glucose induced renal tubular oxidative damage via regulating activation and translocation of p66Shc.Oxidative medicine and cellular longevity · 2014Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Apoptosis is a major mode of cell death occurring during ischemia-reperfusion (I/R) induced injury. The p66(Shc) adaptor protein, which is mediated by PKCβ, has an essential role in apoptosis under oxidative stress. This study aimed to investigate the role of PKCβ2/p66(Shc) pathway in intestinal I/R injury. In vivo, ischemia was induced by superior mesenteric artery occlusion in mice. Ruboxistaurin (PKCβ inhibitor) or normal saline was administered before ischemia. Then blood and gut tissues were collected after reperfusion for various measurements. In vitro, Caco-2 cells were challenged with hypoxia-reoxygenation (H/R) to simulate intestinal I/R. Translocation and activation of PKCβ2 were markedly induced in the I/R intestine. Ruboxistaurin significantly attenuated gut damage and decreased the serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Pharmacological blockade of PKCβ2 suppressed p66(Shc) overexpression and phosphorylation in the I/R intestine. Gene knockdown of PKCβ2 via small interfering RNA (siRNA) inhibited H/R-induced p66(Shc) overexpression and phosphorylation in Caco-2 cells. Phorbol 12-myristate 13-acetate (PMA), which stimulates PKCs, induced p66(Shc) phosphorylation and this was inhibited by ruboxistaurin and PKCβ2 siRNA. Ruboxistaurin attenuated gut oxidative stress after I/R by suppressing the decreased expression of manganese superoxide dismutase (MnSOD), the exhaustion of the glutathione (GSH) system, and the overproduction of malondialdehyde (MDA). As a consequence, ruboxistaurin inhibited intestinal mucosa apoptosis after I/R. Therefore, PKCβ2 inhibition protects mice from gut I/R injury by suppressing the adaptor p66(Shc)-mediated oxidative stress and subsequent apoptosis. This may represent a novel therapeutic approach for the prevention of intestinal I/R injury.
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