Nicotinamide Phosphoribosyltransferase Upregulation by Phenylephrine Reduces Radiation Injury in Submandibular Gland

Bu, Xiang; Han, Lichi; Wang, Xinyue; Tang, Ling; Li, Kailiang; Li, Xiuxiu; Zhao, Xibo; Xia, Mengna; Zhou, Xixi; Zhang, Fuyin; Liu, Ke Jian

doi:10.1016/j.ijrobp.2016.06.2442

Cited by 16 publications

(8 citation statements)

References 27 publications

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“…Moreover, Sirt1 is a negative regulator of p300 expression [92, 181]. Ionizing radiation, cigarette smoke extract, and carbon tetrachloride increase oxidative stress and downregulate Sirt1 gene expression [32, 182, 183]. Nonionizing radiation, such as UV irradiation, also decreases Sirt1 activity [184], which may result in fibrosis.…”

Section: Ros-mediated Histone Modification Changes In Rifmentioning

confidence: 99%

“…The decrease in Sirt1 expression, activity, and changes in its subcellular localization can be linked to changes in Sirt1-catalyzed PTMs influenced by oxidative stress [32, 148, 186–189]. Treatment of fibroblast cells with H 2 O 2 downregulates Sirt1 levels [190], while the use of antioxidants such as resveratrol [191–197], curcumin [198], phenylephrine [182], and vitamin D [199, 200] has been shown to upregulate Sirt1 expression after radiation.…”

Section: Ros-mediated Histone Modification Changes In Rifmentioning

confidence: 99%

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Reactive Oxygen Species Drive Epigenetic Changes in Radiation-Induced Fibrosis

Shrishrimal

Kosmacek

Oberley‐Deegan

2019

Oxidative Medicine and Cellular Longevity

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Radiation-induced fibrosis (RIF) develops months to years after initial radiation exposure. RIF occurs when normal fibroblasts differentiate into myofibroblasts and lay down aberrant amounts of extracellular matrix proteins. One of the main drivers for developing RIF is reactive oxygen species (ROS) generated immediately after radiation exposure. Generation of ROS is known to induce epigenetic changes and cause differentiation of fibroblasts to myofibroblasts. Several antioxidant compounds have been shown to prevent radiation-induced epigenetic changes and the development of RIF. Therefore, reviewing the ROS-linked epigenetic changes in irradiated fibroblast cells is essential to understand the development and prevention of RIF.

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Section: Ros-mediated Histone Modification Changes In Rifmentioning

confidence: 99%

Section: Ros-mediated Histone Modification Changes In Rifmentioning

confidence: 99%

Reactive Oxygen Species Drive Epigenetic Changes in Radiation-Induced Fibrosis

Shrishrimal

Kosmacek

Oberley‐Deegan

2019

Oxidative Medicine and Cellular Longevity

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“…These findings provide evidence that PE pretreatment protects SMGs against mitochondrial-related apoptotic events after exposure to 131 I. SIRT1 and NAMPT signal pathways were involved in the mitochondrial damage induced by 131 I in SMGs, both of which were restored by PE To elucidate the underlying signal pathway through which PE mediates mitochondrial protection in 131 I irradiated SMGs, we examined the possible signal pathways of a 1 -ARs based on our previous study. 4 The expression of p-PI3K, p-AKT, SIRT1, and NAMPT was reduced by 29.0% (P < .05), 67.7% (P < .05), 77.6% (P < .05), and 77.7% (P < .05) in the 131 I irradiated SMGs, respectively, compared with the controls (Fig. 3A-3D).…”

mentioning

confidence: 90%

Phenylephrine Alleviates 131I Radiation Damage in Submandibular Gland Through Maintaining Mitochondrial Homeostasis

Wang

Zhang

et al. 2019

International Journal of Radiation Oncology*Biology*Physics

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131 I ablation therapy for patients with differentiated thyroid cancer commonly leads to radiation sialadenitis. Our findings show that 131 I severely impaired the ultrastructure and the functions of mitochondria in submandibular glands, and the mitochondria-related SIRT1/NAMPT/PGC-1a signal pathways were involved in this process, indicating that 131 I radiation interrupted the mitochondrial homeostasis. Phenylephrine provided cytoprotection against 131 I at the mitochondrial level, suggesting that Purpose: The impairment of the salivary glands is a permanent side effect of 131 I ablation therapy for patients with differentiated thyroid cancer. Effective and safe treatments for protecting the salivary glands against 131 I are currently not available. Mitochondria are susceptible to ionizing radiation, but alterations after 131 I exposure are unknown. Here, we investigated the mechanisms of 131 I damage in submandibular glands (SMGs) and evaluated the cytoprotective effect of phenylephrine (PE) against mitochondrial radiation damage. Methods and Materials: Rats were randomly divided into 4 groups: control, PE alone, 131 I alone, and 131 I with PE pretreatment. The mitochondrial structure of SMGs was observed under transmission electron microscopy. Apoptosis was detected using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. Cytochrome c, cleaved-caspase 3, SIRT1, NAMPT, and PGC-1a protein levels were determined with Western blot and immunohistochemistry. Levels of mitochondrial membrane potential, nicotinamide adenine dinucleotide (NAD), and adenosine triphosphate (ATP) were measured with relevant kits. Results: After exposing rat SMGs to 131 I, the mitochondrial membrane structures were destroyed, the mitochondrial membrane potential decreased, the release of cytochrome c increased, and cleaved-caspase 3 and cell apoptosis were activated. Moreover, the expression of SIRT1, NAMPT, and PGC-1a was downregulated, and the levels of NAD and ATP decreased. In contrast, PE alleviated the 131 I-induced

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“…Nicotinamide phosphoribosyltransferase (NAMPT, also named pre‐B‐cell colony‐enhancing factor) is the most important rate‐limiting enzyme for NAD synthesis 10 . We reported that ionizing radiation (x‐ray and 131 I) significantly reduced the protein expression of NAMPT in rat SMGs 9,11 . Notably, NAM, the amide form of vitamin B3, is a natural substrate of NAMPT 12,13 .…”

Section: Introductionmentioning

confidence: 99%

Nicotinamide mitigates radiation injury in submandibular gland by protecting mitochondrial structure and functions

Wang

Liu

Zhang

et al. 2022

J Oral Pathology Medicine

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Background: Radiation damage to salivary gland is inevitable in head and neck cancer patients receiving radiotherapy. Safe and effective treatments for protecting salivary glands from radiation are still unavailable. Mitochondrial damage is a critical mechanism in irradiated salivary gland; however, treatment targeting mitochondria has not received much attention. Nicotinamide is a key component of the mitochondrial metabolism. Here, we investigated the effects and underlying mechanisms of nicotinamide on protecting irradiated submandibular gland. Methods: Submandibular gland cells and tissues were randomly divided into four groups: control, nicotinamide alone, radiation alone, and radiation with nicotinamide pretreatment. Cell viability was detected by PrestoBlue cell viability reagent. Histopathological alterations were observed with HE staining. Pilocarpine-stimulated saliva was measured from Wharton's duct. Cell apoptosis was determined by flow cytometry and terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. Nicotinamide phosphoribosyl transferase was examined with immunofluorescence. The levels of nicotinamide adenine dinucleotide, mitochondrial membrane potential, and adenosine triphosphate were measured with the relevant kits. The mitochondrial ultrastructure was observed under transmission electron microscopy.Results: Nicotinamide significantly mitigated radiation damage both in vitro and in vivo. Also, nicotinamide improved saliva secretion and reduced radiation-induced apoptosis in irradiated submandibular glands. Moreover, nicotinamide improved nicotinamide phosphoribosyl transferase and the levels of nicotinamide adenine dinucleotide/adenosine triphosphate and mitochondrial membrane potential, all of which were decreased by radiation in submandibular gland cells. Importantly, nicotinamide protected the mitochondrial ultrastructure from radiation. Conclusion:These findings demonstrate that nicotinamide alleviates radiation damage in submandibular gland by replenishing nicotinamide adenine dinucleotide and maintaining mitochondrial function and ultrastructure, suggesting that nicotinamide could be used as a prospective radioprotectant for preventing radiation sialadenitis.

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Nicotinamide Phosphoribosyltransferase Upregulation by Phenylephrine Reduces Radiation Injury in Submandibular Gland

Cited by 16 publications

References 27 publications

Reactive Oxygen Species Drive Epigenetic Changes in Radiation-Induced Fibrosis

Reactive Oxygen Species Drive Epigenetic Changes in Radiation-Induced Fibrosis

Phenylephrine Alleviates 131I Radiation Damage in Submandibular Gland Through Maintaining Mitochondrial Homeostasis

Nicotinamide mitigates radiation injury in submandibular gland by protecting mitochondrial structure and functions

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