Cobalt-60 gamma radiation increased the nitric oxide generation in cultured rat vascular smooth muscle cells

Zhong, Guang Zhen; Chen, Feng Rong; Bu, Ding Fang; Wang, Shu Heng; Pang, Yiming; Tang, Chao

doi:10.1016/j.lfs.2003.08.049

Cited by 9 publications

(4 citation statements)

References 13 publications

(17 reference statements)

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“…Our results and postulates are consistent with previously published work examining the effect of irradiation on the role of the endothelium on vascular function (2,13,21,27,40,41). Interestingly, one study demonstrated an increase in NO generation after irradiation, but this was performed in cultured vascular smooth muscle and therefore the cells may or may not have been in the contractile phenotype (47).…”

mentioning

confidence: 99%

Ionizing radiation alters myofilament calcium sensitivity in vascular smooth muscle: potential role of protein kinase C

Soloviev¹,

Tishkin²,

Zelensky³

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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Radiation exposure increases vascular responsiveness, and this change involves endothelial damage, as well as direct effects on vascular smooth muscle. In this study, we tested the hypothesis that myofilament Ca(2+) sensitivity in vascular smooth muscle is increased from single whole body gamma irradiation (6 Gy). We measured contractile responses from intact and permeabilized rat thoracic aortic rings combined with cytosolic Ca(2+) ([Ca(2+)](i)) measurements. The sensitivity to KCl and phenylephrine increased significantly in tissues from animals on the 9th and 30th days postirradiation compared with control. Irradiation also significantly increased Ca(2+) sensitivity in beta-escin permeabilized smooth muscle on the 9th and 30th days postirradiation. Inhibitors of protein kinase C, chelerythrine, and staurosporine, had no effect on the pCa-tension curves in control permeabilized tissues but significantly decreased Ca(2+) sensitivity in permeabilized tissues on the 9th and 30th days postirradiation. Phorbol dibutyrate (PDBu, 10(-7) M) increased Ca(2+) sensitivity in control skinned smooth muscle but was without effect in irradiated vascular rings. Simultaneous measurement of contractile force and [Ca(2+)](i) showed that myofilament Ca(2+) sensitivity defined as the ratio of force change to [Ca(2+)](i) significantly increased following gamma-irradiation. PDBu (10(-6) M) stimulation of intact aorta produced a sustained contraction, while the increase in [Ca(2+)](i) was transient. In irradiated tissues, PDBu-induced contractions were greater than those seen in control tissues but there was no elevation in [Ca(2+)](i). Taken together, these data strongly support the hypothesis that irradiation increases the sensitivity of vascular smooth muscle myofilaments to Ca(2+) and this effect is dependent on activation of protein kinase C.

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mentioning

confidence: 99%

Ionizing radiation alters myofilament calcium sensitivity in vascular smooth muscle: potential role of protein kinase C

Soloviev¹,

Tishkin²,

Zelensky³

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Reports in the literature showed that ionizing radiation causes a large increase in NO levels, and its excessive production can lead to cytotoxicity and induce widespread inflammation [29]. Upregulation of the inducible form of nitric oxide synthase (iNOS) or Nos2 was observed in cultured smooth muscle cells exposed to gamma radiation [30]. Ultraviolet ray exposure of skin cells was also found to induce Nos2 expression [31].…”

Section: Discussionmentioning

confidence: 99%

PrC-210 Protects against Radiation-Induced Hematopoietic and Intestinal Injury in Mice and Reduces Oxidative Stress

et al. 2023

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The development of safe, orally available, and effective prophylactic countermeasures to protect our warfighters is an unmet need because there is no such FDA-approved countermeasure available for use. Th 1-Propanethiol, 3-(methylamino)-2-((methylamino)methyl) (PrC-210), a synthetic small molecule, is a member of a new family of aminothiols designed to reduce toxicity while scavenging reactive oxygen species (ROS). Our study investigated the protective role of a single oral administration of PrC-210 against radiation-induced hematopoietic and intestinal injury in mice. Pre-treatment with PrC-210 significantly improved the survival of mice exposed to a lethal dose of radiation. Our findings indicated that the radioprotective properties of PrC-210 are achieved by accelerating the recovery of the hematopoietic system, stimulating bone marrow progenitor cells, and ameliorating additional biomarkers of hematopoietic injury. PrC-210 pre-treatment reduced intestinal injury in mice exposed to a lethal dose of radiation by restoring jejunal crypts and villi, reducing translocation of bacteria to the spleen, maintaining citrulline levels, and reducing the sepsis marker serum amyloid A (SAA) in serum. Finally, PrC-210 pre-treatment led to a significant reduction (~10 fold) of Nos2 expression (inducible nitric oxide) in the spleen and decreased oxidative stress by enhancing the antioxidant defense system. These data support the further development of PrC-210 to receive approval from the FDA to protect warfighters and first responders from exposure to the harmful effects of ionizing radiation.

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“…c-irradiation can increase COX-2 and/or iNOS expression (Zhong et al 2004), but the effects on gene expression of pro-inflammatory proteins, such as COX-2, iNOS, VCAM1, ICAM1, and E-selectin, has not been reported. Here, c-irradiation up-regulated COX-2 and iNOS expression as well as the pro-inflammatory genes, VCAM1, ICAM1, and E-selectin.…”

Section: Discussionmentioning

confidence: 99%

Molecular activation of NF-κB, pro-inflammatory mediators, and signal pathways in γ-irradiated mice

Chung

Kim

et al. 2009

Biotechnol Lett

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The effects of gamma-irradiation on inflammatory gene expression, including NF-kappaB activation, in the kidney of C57/BL6 mice exposed to 1-9 Gy doses of (60)Co gamma-irradiation. Radiation enhanced the NF-kappaB activation and oxidative stress caused a dose-dependent disruption in the redox balance. The significance of this study is the new molecular information gained on gamma-irradiation effects through the activation of pro-inflammatory genes by NF-kappaB via the MAPK signaling pathway. Considering the exquisite sensitivity of NF-kappaB and other pro-inflammatory mediators to the redox status, we conclude that the activation of inflammatory processes by irradiation is likely initiated by increased oxidative stress.

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Cobalt-60 gamma radiation increased the nitric oxide generation in cultured rat vascular smooth muscle cells

Cited by 9 publications

References 13 publications

Ionizing radiation alters myofilament calcium sensitivity in vascular smooth muscle: potential role of protein kinase C

Ionizing radiation alters myofilament calcium sensitivity in vascular smooth muscle: potential role of protein kinase C

PrC-210 Protects against Radiation-Induced Hematopoietic and Intestinal Injury in Mice and Reduces Oxidative Stress

Molecular activation of NF-κB, pro-inflammatory mediators, and signal pathways in γ-irradiated mice

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