Mechanism of apoptosis involved in gastric mucosal lesions in Tibetans with high-altitude polycythemia

Li, Kang; Gesang, Luobu; Cai, He

doi:10.3892/etm.2017.4996

Cited by 9 publications

(14 citation statements)

References 25 publications

(23 reference statements)

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“…Comparing with our reported work [26, 33], the population size was increased from 6 and 24 to 45 subjects in the present study. Furthermore, the color of brown lesions under the mucosa in upper gastrointestinal tract was much darker than before reported in HAPC patients (Figure 1).…”

Section: Discussionsupporting

confidence: 56%

“…Glandular epithelial cells of gastric mucosa were extracted and the protein levels of HIF-1A were analyzed using Western Blot. The total protein was obtained using cocktail after the cells were lysed for 3 times by freezing and thawing [26]. Supernatant protein was separated using SDS-PAGE and transferred to a PVDF membrane, and blocked by 2.5% nonfat dry milk for half an hour.…”

Section: Methodsmentioning

confidence: 99%

“…The slides of mucosal issues were treated with 10 μ g/ml proteinase K (Sigma, St Louis, MO, USA) for 15 min at RT and washed for 2 min with ddH 2 O. Endogenous peroxidases were deactivated by 2% of hydrogen peroxide for 5 min. The sections were rinsed with ddH 2 O, and immersed in TDT buffer [26]. TDT (200 U/mL; Takara, Tokyo, TUNEL assay for apoptosis of gastric mucosa) and biotinylated dUTP (0.01 mM BMY) in TDT buffer were then added to the sections, and incubated in a humid atmosphere at 37°C for 1 h. The reaction was stopped by using TB buffer (0.3 M NaCl, 0.04 M sodium citrate) for 20 min.…”

Section: Methodsmentioning

confidence: 99%

“…After being rinsed in ddH 2 O, the slides were stained with hematoxylin for half an hour at 37°C. Dehydration was performed according to a previous report [26]. The tissue sections were then mounted in Permount (Fisher Scientific, Pittsburgh, PA, USA).…”

Section: Methodsmentioning

confidence: 99%

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Gastric Mucosal Lesions in Tibetans with High-Altitude Polycythemia Show Increased HIF-1A Expression and ROS Production

Cai

2019

BioMed Research International

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Background. Living at a high plateau in a very hostile environment and low oxygen levels often leads to the development of high-altitude polycythemia (HAPC) and gastric mucosal lesions caused by high-level reactive oxygen species (ROS). Hypoxia-inducible factor-1A (HIF-1A) helps maintain oxygen homeostasis by promoting the transcription of various genes and can be affected by ROS levels. To evaluate the molecular mechanism by which HAPC causes the gastric mucosal lesions, the expression of HIF-1A was measured in Tibetans with HAPC and in healthy subjects. Ultrastructural, histopathological, and immunohistochemical analyses were performed in the gastric tissues of both groups, and the expression of HIF-1A in the gastric mucosa was detected using qPCR and Western Blot. Results. The microvessel density and average diameter of gastric mucosal vessels were significantly greater in the HAPC patients than in the healthy subjects (p < 0.05). The number of red blood cells in the gastric mucosa was also significantly higher in the HAPC group than in the healthy subjects (p < 0.05). In addition, the density of the mitochondrial vacuoles and endoplasmic reticulum and pathological apoptosis were significantly increased in the gastric cells from HAPC patients compared to those from the healthy subjects. The levels of ROS and HIF-1A in the gastric mucosa were increased in HAPC patients compared to those in controls (p < 0.05). Conclusions. An increased level of HIF-1A was associated with HAPC development in the stomach of Tibetans living at a high altitude. ROS upregulated the levels of HIF-1A. Thus, ROS-mediated HIF-1A signaling transduction may be the mechanism associated with HAPC-induced gastric lesions.

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Section: Discussionsupporting

confidence: 56%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Gastric Mucosal Lesions in Tibetans with High-Altitude Polycythemia Show Increased HIF-1A Expression and ROS Production

Cai

2019

BioMed Research International

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“…Substantial and growing evidence has confirmed that low-frequency pulsed electromagnetic fields (PEMFs), as an alternative noninvasive method, can efficiently induce tissue regeneration and cell proliferation [10–12]. Therefore, the positive effects of PEMFs on the healing of certain tissue damage have been investigated in numerous animal experiments [13, 14]. In addition, clinical investigations have confirmed the efficacy of PEMFs in repairing impaired tissues [4, 15].…”

Section: Introductionmentioning

confidence: 99%

Effects of Low-Frequency Pulsed Electromagnetic Fields on High-Altitude Stress Ulcer Healing in Rats

Jiao

Yin

et al. 2019

BioMed Research International

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High-altitude stress ulcer (HSU) has constantly been a formidable clinical challenge for high-altitude and severe hypoxia. Pulsed electromagnetic fields (PEMFs) have been verified to have the ability to penetrate tissues, and the biological effects have been confirmed effective on various tissue restorations. However, the therapeutic effect of PEMFs on HSU has been rarely reported. This study aimed to evaluate the effects of PEMFs on HSU healing systematically. Sprague–Dawley rats were assigned to control, HSU, and HSU+PEMF groups. The HSU models were induced by restraint stress under low-pressure hypoxia. The HSU+PEMF group was subjected to PEMF exposure. During the HSU healing, gastric juice pH values, ulcer index (UI), and histopathologic changes were investigated. Furthermore, tumor necrosis factor-α (TNF-α) was determined to analyze the severity of gastric membrane inflammations. Norepinephrine (NE), which influences gastric acid secretion, was measured. Results indicated the UI of the HSU+PEMF decreased faster than that of the HSU group. Histopathologic observation suggested that the ulcer tissue healing is faster in the HSU+PEMF group than in the HSU group. The TNF-α/total protein results revealed that the inflammation of the HSU+PEMF group is suppressed effectively. The pH values are higher in the HSU+PEMF group than in the HSU, as confirmed by NE examination. The results indicated that low-frequency PEMFs can penetrate stomach tissues to relieve the symptoms of HSU and promote the regeneration of disturbed tissues, thus implying the clinical potential of PEMF therapy for HSU treatment.

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Ameliorating effects of the HIF-2α inhibitor PT2385 on high-altitude polycythemia

Li,

Luobu,

et al. 2024

European Journal of Pharmaceutical Sciences

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Mechanism of apoptosis involved in gastric mucosal lesions in Tibetans with high-altitude polycythemia

Cited by 9 publications

References 25 publications

Gastric Mucosal Lesions in Tibetans with High-Altitude Polycythemia Show Increased HIF-1A Expression and ROS Production

Gastric Mucosal Lesions in Tibetans with High-Altitude Polycythemia Show Increased HIF-1A Expression and ROS Production

Effects of Low-Frequency Pulsed Electromagnetic Fields on High-Altitude Stress Ulcer Healing in Rats

Ameliorating effects of the HIF-2α inhibitor PT2385 on high-altitude polycythemia

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