Increased Myocardial Dysfunction After Ischemia-Reperfusion in Mice Lacking Glucose-6-Phosphate Dehydrogenase

Jain, Mohit; Cui, Lei; Brenner, Daniel; Wang, Bo; Handy, Diane E.; Leopold, Jane A.; Loscalzo, Joseph; Apstein, Carl S.; Liao, Ronglih

doi:10.1161/01.cir.0000112605.43318.ca

Cited by 117 publications

(99 citation statements)

References 44 publications

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“…MnTMPyP is a SOD mimetic that protects the heart from ischemia/reperfusion injury (31). In the present study, MnTMPyP reduced the post-ischemic lipid peroxidation and the tissue levels of hydrogen peroxide in the kidney.…”

Section: Discussionsupporting

confidence: 57%

Orchiectomy Attenuates Post-ischemic Oxidative Stress and Ischemia/Reperfusion Injury in Mice

Kim

Kil

Seok

et al. 2006

Journal of Biological Chemistry

115

116

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Males are much more susceptible to ischemia/reperfusion (I/R)-induced kidney injury when compared with females. Recently we reported that the presence of testosterone, rather than the absence of estrogen, plays a critical role in gender differences in kidney susceptibility to I/R injury in mice. Although reactive oxygen species and antioxidant defenses have been implicated in I/R injury, their roles remain to be defined. Here we report that the orchiectomized animal had significantly less lipid peroxidation and lower hydrogen peroxide levels in the kidney 4 and 24 h after 30 min of bilateral renal ischemia when compared with intact or dihydrotestosterone-treated orchiectomized males. The post-ischemic kidney expression and activity of manganese superoxide dismutase (MnSOD) in orchiectomized mice was much greater than in intact or dihydrotestosterone-administered orchiectomized mice. Four hours after 30 min of bilateral ischemia, superoxide formation was significantly lower in orchiectomized mice than in intact mice. In Madin-Darby canine kidney cells, a kidney epithelial cell line, 1 mM H 2 O 2 decreased MnSOD activity, an effect that was potentiated by pretreatment with dihydrotestosterone. Orchiectomy prevented the post-ischemic decrease of catalase activity. Treatment of male mice with manganese(III) tetrakis(1-methyl-4-pyridyl)porphyrin (MnTMPyP), a SOD mimetic, reduced the post-ischemic increase of plasma creatinine, lipid peroxidation, and tissue hydrogen peroxide. These results suggest that orchiectomy accelerates the post-ischemic activation of MnSOD and reduces reactive oxygen species and lipid peroxidation, resulting in reduced kidney susceptibility to I/R injury.Gender differences in disease susceptibility have been well characterized in many cardiovascular diseases (1-3). The increased risk for cardiovascular diseases in men and postmenopausal women (4) has been attributed primarily to lack of estrogen-mediated protection (5-7). Recently we demonstrated that male mice are much more susceptible to kidney ischemia/reperfusion (I/R) 5 injury when compared with female mice (8), and that orchiectomy decreases kidney susceptibility to I/R injury (9), whereas ovariectomy has no effect on kidney susceptibility to I/R injury (8). Testosterone administration to orchiectomized male or female mice reverses the protective phenotype, increasing susceptibility to kidney I/R injury. We concluded that the presence of testosterone, rather than the absence of estrogen, plays a critical role in the gender differences in kidney susceptibility to I/R injury. The detailed molecular mechanisms responsible for this testosterone effect remain to be defined.Ischemia/reperfusion markedly increases the production of reactive oxygen species (ROS) including superoxide anions, hydroxyl radicals, hypochlorous acid, hydrogen peroxide, and peroxynitrite (10). The abnormal excessive production of ROS results in lipid peroxidation, leukocyte activation, endothelial cell damage, and cytokine production, all of which contribute to tissue ...

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Section: Discussionsupporting

confidence: 57%

Orchiectomy Attenuates Post-ischemic Oxidative Stress and Ischemia/Reperfusion Injury in Mice

Kim

Kil

Seok

et al. 2006

Journal of Biological Chemistry

115

116

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“…The importance of this metabolic pathway in tumorigenesis has been reported. 14,41 The key enzyme of the oxidative branch, G6PDH, has been broadly studied under different physiological situations such as ischemia, 42 growth factor activation, 43 hyperglycaemia 44 and apoptosis. 45 Furthermore TKT, which is the key enzyme of the nonoxidative branch, has also been related to diabetic retinopathy 46 and Wernicke-Korsakoff syndrome.…”

Section: Discussionmentioning

confidence: 99%

Modulation of pentose phosphate pathway during cell cycle progression in human colon adenocarcinoma cell line HT29

Vizán

Alcarraz-Vizán

Díaz-Moralli

et al. 2009

Intl Journal of Cancer

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Cell cycle regulation is dependent on multiple cellular and molecular events. Cell proliferation requires metabolic sources for the duplication of DNA and cell size. However, nucleotide reservoirs are not sufficient to support cell duplication and, therefore, biosynthetic pathways should be upregulated during cell cycle. Here, we reveal that glucose-6-phosphate dehydrogenase (G6PDH) and transketolase (TKT), the 2 key enzymes of oxidative and nonoxidative branches of the pentose phosphate pathway (PPP), respectively, which is necessary for nucleotide synthesis, are enhanced during cell cycle progression of the human colon cancer cell line HT29. These enhanced enzyme activities coincide with an increased ratio of pentose monophosphate to hexose monophosphate pool during late G1 and S phase, suggesting a potential role for pentose phosphates in proliferating signaling. Isotopomeric analysis distribution of nucleotide ribose synthesized from 1,2-13 C 2 -glucose confirms the activation of the PPP during late G1 and S phase and reveals specific upregulation of the oxidative branch. Our data sustain the idea of a critical oxidative and nonoxidative balance in cancer cells, which is consistent with a late G1 metabolic check point. The distinctive modulation of these enzymes during cell cycle progression may represent a new strategy to inhibit proliferation in anticancer treatments. ' 2009 UICC

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“…After 15 min of stabilization, hearts were subjected to 15 min of zero-flow ischemia, followed by 10 or 30 min of reperfusion as described previously (23).…”

Section: Methodsmentioning

confidence: 99%

Cardiac Endothelial Cells Regulate Reactive Oxygen Species-induced Cardiomyocyte Apoptosis through Neuregulin-1β/erbB4 Signaling

Kuramochi

Coté

Guo

et al. 2004

Journal of Biological Chemistry

Self Cite

175

152

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Neuregulin (NRG)-1␤ has a prosurvival effect on cardiac myocytes via the phosphatidylinositol-3-kinase/Akt pathway, but the physiological regulators of this system in the intact heart are unknown. In this study, we tested the hypothesis that reactive oxygen species regulate NRG/erbB signaling. We used isolated adult rat ventricular myocytes (ARVMs) or cardiac microvascular endothelial cells (CMECs) in monoculture, or together in coculture. H 2 O 2 induced NRG-1␤ release from CMECs in a concentration-dependent manner, and conditioned medium from H 2 O 2 -treated CMEC activated ARVM erbB4. NRG-1␤ release occurred via proteolytic cleavage of 115-kDa transmembrane NRG-1␤ and was inhibited by the metalloproteinase inhibitor 1,10-phenanthroline. In myocyte monoculture, H 2 O 2 induced erbB4-dependent, but NRG-independent, activation of Akt. To elucidate the bioactivity of CMEC-derived NRG-1␤ on ARVMs, we examined H 2 O 2 -induced myocyte apoptosis in co-culture using an antibody to NRG-1␤. The percentages of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells were significantly higher in the anti-NRG-1␤ group than in the control group. The change in apoptosis induced by anti-NRG-1␤ in co-culture was similar in magnitude to the protection of myocytes by addition of recombinant NRG-1␤ to ARVM monocultures. Activation of NRG/erbB paracrine signaling was also seen in the intact heart subjected to oxidative stress by ischemia-reperfusion injury. Isolated perfused mouse hearts subjected to 15 min of ischemia, followed by 30 min of reperfusion, showed complete proteolytic cleavage of 115-kDa NRG-1␤, with concomitant erbB4 phosphorylation. These results demonstrate that reactive oxygen species activate NRG-1␤/erbB4 paracrine signaling in the heart and suggest that this system is involved in cardiac adaptation to oxidative stress. Neuregulin-1 (NRG)1 /erbB signaling is essential for cardiac development (1-5). Moreover, cardiotoxicity of trastuzumab (Herceptin), an erbB2-targeted antibody used in treatment of erbB2-positive cancer, suggests that this pathway also plays a role in the regulation of cardiac structure and function in the postnatal heart (6). Cardiac microvascular endothelial cells (CMECs) express NRG (7), and recombinant NRG-1␤ protects myocytes against anthracycline-and ␤-adrenergic receptor-induced cell injury and death (8 -10). This prosurvival effect of NRG-1␤ occurs through the activation of erbB2 and erbB4 receptor tyrosine kinases in myocytes with downstream signaling in the phosphatidylinositol-3-kinase/Akt pathway. The in vivo role of erbB signaling in cardioprotection is further supported by the finding that mice with a cardiac-specific erbB2 conditional knock-out survive to birth but have accelerated heart failure after injury by pressure-overload or Adriamycin (11, 12). These observations suggest that the NRG/erbB pathway acts as a stress-responsive signal between CMECs and myocytes to maintain cell survival and cardiac function.We have cloned eight isoforms of NRG-1␤ fr...

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Increased Myocardial Dysfunction After Ischemia-Reperfusion in Mice Lacking Glucose-6-Phosphate Dehydrogenase

Cited by 117 publications

References 44 publications

Orchiectomy Attenuates Post-ischemic Oxidative Stress and Ischemia/Reperfusion Injury in Mice

Orchiectomy Attenuates Post-ischemic Oxidative Stress and Ischemia/Reperfusion Injury in Mice

Modulation of pentose phosphate pathway during cell cycle progression in human colon adenocarcinoma cell line HT29

Cardiac Endothelial Cells Regulate Reactive Oxygen Species-induced Cardiomyocyte Apoptosis through Neuregulin-1β/erbB4 Signaling

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