scholarly journals Enhanced H3K4 Trimethylation in TNF-α Promoter Gene Locus with Cell Apoptosis in the Ventral-Medial Striatum following Opioid Withdrawal of Neonatal Rat Offspring from Morphine-Addicted Mothers

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Pei-Ling Wu ◽  
Jau-Ling Suen ◽  
Chun-Hwa Yang ◽  
Kuang-Che Kuo ◽  
Yu-Chen S. H. Yang ◽  
...  
Keyword(s):  
Cell Apoptosis ◽  
Gene Locus ◽  
Neural Cell ◽  
Opioid Withdrawal ◽  
Neonatal Rat ◽  
Gene Expressions ◽  
Adult Rats ◽  
Rat Offspring ◽  
Tnf Α ◽  
Promoter Gene

Prenatal opioid exposure might disturb epigenetic programming in the brain of neonatal offspring with various consequences for gene expressions and behaviors. This study determined whether altered trimethylation of histone 3 at lysine 4 (H3K4me3) in the promoter of the tumor necrosis factor-α (tnf-α) gene with neural cell apoptosis was involved in the ventral-medial striatum, an important brain region for withdrawal symptoms, of neonatal rat offspring from morphine-addicted mothers. Female adult rats were injected with morphine before gestation and until 14 days after giving birth. On postnatal day 14 (P14), rat offspring from morphine-addicted mothers were subjected to an opioid-withdrawal protocol and were analyzed 2 or 8 h after administration of that protocol. Expressions of the TNF-α protein, H3K4me3 in the tnf-α promoter gene, and neural cell apoptosis within the ventral-medial striatum of neonatal rat offspring were evaluated. In the absence of significant opioid withdrawal (2 h after initiation of the opioid-withdrawal protocol on P14), prenatal morphine exposure led to increased levels of H3K4me3 in the tnf-α promoter gene, of the TNF-α protein, and of neural cell apoptosis within the ventral-medial striatum of neonatal rat offspring. Following opioid withdrawal (8 h after initiation of the opioid-withdrawal protocol on P14), differential expression of H3K4me3 in the tnf-α promoter gene locus and upregulation of the level of TNF-α protein expression were further enhanced in these offspring. In addition, increased levels of caspase-3 and neural cell apoptosis were also observed. Taken together, this study revealed that prenatal opioid exposure can activate an epigenetic histone mechanism which regulates proinflammatory factor generation, which hence, led to cell apoptotic damage within the ventral-medial striatum of neonatal rat offspring from morphine-addicted mothers. More importantly, the opioid-withdrawal episode may provide augmented effects for the abovementioned alterations and could lead to deleterious effects in the neonatal brain of such offspring.

scholarly journals miR-21-5p Under-Expression in Patients with Obstructive Sleep Apnea Modulates Intermittent Hypoxia with Re-Oxygenation-Induced-Cell Apoptosis and Cytotoxicity by Targeting Pro-Inflammatory TNF-α-TLR4 Signaling

2020 ◽  
Vol 21 (3) ◽  
pp. 999
Author(s):  
Yung-Che Chen ◽  
Po-Yuan Hsu ◽  
Mao-Chang Su ◽  
Chien-Hung Chin ◽  
Chia-Wei Liou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Cell Apoptosis ◽  
Intermittent Hypoxia ◽  
Target Genes ◽  
Apnea Hypopnea Index ◽  
Gene Expressions ◽  
Obstructive Sleep ◽  
Tnf Α

The purpose of this study is to explore the anti-inflammatory role of microRNAs (miR)-21 and miR-23 targeting the TLR/TNF-α pathway in response to chronic intermittent hypoxia with re-oxygenation (IHR) injury in patients with obstructive sleep apnea (OSA). Gene expression levels of the miR-21/23a, and their predicted target genes were assessed in peripheral blood mononuclear cells from 40 treatment-naive severe OSA patients, and 20 matched subjects with primary snoring (PS). Human monocytic THP-1 cell lines were induced to undergo apoptosis under IHR exposures, and transfected with miR-21-5p mimic. Both miR-21-5p and miR-23-3p gene expressions were decreased in OSA patients as compared with that in PS subjects, while TNF-α gene expression was increased. Both miR-21-5p and miR-23-3p gene expressions were negatively correlated with apnea hypopnea index and oxygen desaturation index, while TNF-α gene expression positively correlated with apnea hypopnea index. In vitro IHR treatment resulted in decreased miR-21-5p and miR-23-3p expressions. Apoptosis, cytotoxicity, and gene expressions of their predicted target genes—including TNF-α, ELF2, NFAT5, HIF-2α, IL6, IL6R, EDNRB, and TLR4—were all increased in response to IHR, while all were reversed with miR-21-5p mimic transfection under IHR condition. The findings provide biological insight into mechanisms by which IHR-suppressed miRs protect cell apoptosis via inhibit inflammation, and indicate that over-expression of the miR-21-5p may be a new therapy for OSA.

scholarly journals Expression of miR-195 and its target gene Bcl-2 in human intervertebral disc degeneration and their effects on nucleus pulposus cell apoptosis

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Xue-Lin Lin ◽  
Zhao-Yun Zheng ◽  
Qing-Shan Zhang ◽  
Zhen Zhang ◽  
You-Zhi An
Keyword(s):  
Cell Proliferation ◽  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Rat Model ◽  
Cell Apoptosis ◽  
Intervertebral Disc Degeneration ◽  
Target Gene ◽  
Blank Group ◽  
Tnf Α

Abstract Objective To investigate the expression of miR-195 and its target gene Bcl-2 in intervertebral disc degeneration (IVDD) and its effect on nucleus pulposus (NP) cell apoptosis. Methods The expressions of miR-195 and Bcl-2 in NP tissues of IVDD patients were quantified by qRT-PCR and western blotting, respectively. NP cells were divided into blank group, TNF-α group, TNF-α + miR-NC group, TNF-α + siBcl-2 group, and TNF-α + miR-195 inhibitors + siBcl-2 group. Cell proliferation was detected by MTT assay, cell apoptosis evaluated by flow cytometry, and mitochondrial membrane potential (MMP) tested by JC-1 staining. Moreover, the function of miR-195 on IVDD in vivo was investigated using a puncture-induced IVDD rat model. Results IVDD patients had significantly increased miR-195 expression and decreased Bcl-2 protein expression in NP tissues. The expression of miR-195 was negatively correlated with the expression of Bcl-2 in IVDD patients. Dual-luciferase reporter gene assay indicated that Bcl-2 was a target gene of miR-195. In comparison with blank group, TNF-α group showed decreased cell proliferation and MMP, increased cell apoptosis, upregulated expression of miR-195, Bax, and cleaved caspase 3, and downregulated Bcl-2 protein, while these changes were attenuated by miR-195 inhibitors. Additionally, siBcl-2 can reverse the protective effect of miR-195 inhibitors on TNF-α-induced NP cells. Besides, inhibition of miR-195 alleviated IVDD degeneration and NP cell apoptosis in the rat model. Conclusion MiR-195 was significantly upregulated in NP tissues of IVDD patients, and inhibition of miR-195 could protect human NP cells from TNF-α-induced apoptosis via upregulation of Bcl-2.

scholarly journals In Vitro Evaluation of the Anti-Inflammatory Effect of KMUP-1 and in Vivo Analysis of Its Therapeutic Potential in Osteoarthritis

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 615
Author(s):  
Shang-En Huang ◽  
Erna Sulistyowati ◽  
Yu-Ying Chao ◽  
Bin-Nan Wu ◽  
Zen-Kong Dai ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Antioxidant Properties ◽  
Serum Levels ◽  
Gene Expressions ◽  
Tnf Α ◽  
Anti Inflammatory

Osteoarthritis is a degenerative arthropathy that is mainly characterized by dysregulation of inflammatory responses. KMUP-1, a derived chemical synthetic of xanthine, has been shown to have anti-inflammatory and antioxidant properties. Here, we aimed to investigate the in vitro anti-inflammatory and in vivo anti-osteoarthritis effects of KMUP-1. Protein and gene expressions of inflammation markers were determined by ELISA, Western blotting and microarray, respectively. RAW264.7 mouse macrophages were cultured and pretreated with KMUP-1 (1, 5, 10 μM). The productions of TNF-α, IL-6, MMP-2 and MMP- 9 were reduced by KMUP-1 pretreatment in LPS-induced inflammation of RAW264.7 cells. The expressions of iNOS, TNF-α, COX-2, MMP-2 and MMP-9 were also inhibited by KMUP-1 pretreatment. The gene expression levels of TNF and COX families were also downregulated. In addition, KMUP-1 suppressed the activations of ERK, JNK and p38 as well as phosphorylation of IκBα/NF-κB signaling pathways. Furthermore, SIRT1 inhibitor attenuated the inhibitory effect of KMUP-1 in LPS-induced NF-κB activation. In vivo study showed that KMUP-1 reduced mechanical hyperalgesia in monoiodoacetic acid (MIA)-induced rats OA. Additionally, KMUP-1 pretreatment reduced the serum levels of TNF-α and IL-6 in MIA-injected rats. Moreover, macroscopic and histological observation showed that KMUP-1 reduced articular cartilage erosion in rats. Our results demonstrated that KMUP-1 inhibited the inflammatory responses and restored SIRT1 in vitro, alleviated joint-related pain and cartilage destruction in vivo. Taken together, KMUP-1 has the potential to improve MIA-induced articular cartilage degradation by inhibiting the levels and expression of inflammatory mediators suggesting that KMUP-1 might be a potential therapeutic agent for OA.

Homeostatic control of manganese excretion in the neonatal rat

1987 ◽  
Vol 252 (5) ◽  
pp. R842-R847 ◽  
Author(s):  
N. Ballatori ◽  
E. Miles ◽  
T. W. Clarkson
Keyword(s):  
Trace Metal ◽  
Biliary Excretion ◽  
Intraperitoneal Injection ◽  
Neonatal Rat ◽  
Abrupt Increase ◽  
Adult Rats ◽  
Tracer Dose ◽  
Diminished Capacity ◽  
Carrier Free ◽  
Old Rats

Previous studies in neonatal and suckling animals showed that immature animals have a greatly diminished capacity to excrete manganese and therefore were considered to be unable to regulate tissue manganese concentrations. In contrast, the present studies indicate that suckling rats have the capacity to excrete excess manganese at rates nearly comparable to those of adults. Eight- to 10-day-old rats given a tracer dose of 54MnCl2 (essentially carrier free), either via gavage or by intraperitoneal injection showed little elimination of the 54Mn until the 18-19th day of life, when there was an abrupt increase in the rate of the metal's excretion. However, when manganese was given in doses of 1 and 10 mg/kg, the young animals excreted from 30-70% of the dose in only 4 days, at which time a new rate of excretion was achieved. This enhanced rate of excretion remained constant until the 18-19th day of life, when it was again accelerated. Biliary excretion of manganese, the primary route for the elimination of the metal, was only 30-60% lower in 14-day-old rats compared with adults at doses ranging from tracer to 10 mg 54Mn/kg. For both the 14-day-old and adult rats, an apparent biliary transport maximum was reached at a dose of 10 mg Mn/kg. These studies indicate that the excretory pathways for manganese are well developed in the neonatal rat. The avid retention of tracer quantities of manganese by the neonate may be a consequence of the scarcity of this essential trace metal in its diet.

Pituitary-adrenal response to bacterial endotoxin in developing rats

1988 ◽  
Vol 255 (4) ◽  
pp. E525-E530 ◽  
Author(s):  
L. Witek-Janusek
Keyword(s):  
Plasma Corticosterone ◽  
Neonatal Rat ◽  
Bacterial Endotoxin ◽  
Plasma Acth ◽  
Adult Rats ◽  
Age Related ◽  
Corticosterone Response ◽  
Adrenal Response ◽  
Old Rats ◽  
Related Pattern

The neonatal rat is very sensitive to the lethal effects of bacterial endotoxin. Because of the adaptive importance of pituitary-adrenal secretions to stress, this study examined the ontogeny of the plasma corticosterone and adrenocorticotropic hormone (ACTH) responses to endotoxin. The lethal sensitivity of young rats to endotoxin ranged from 0.5 to 30 mg/kg (ip) in the 1- to 21-day-old rat. After endotoxin treatment, the 1- and 2-day-old rat showed marked elevations of corticosterone similar in magnitude to that seen in 21-day-old and adult rats; however, significantly depressed corticosterone increments were observed in the 5-, 10-, and 14-day-old rats. This age-related pattern of adrenocortical secretion was correlated with the developing rat's corticosterone response to exogenous ACTH. In contrast, endotoxin administered to 5-, 10-, and 14-day-old rats resulted in increments of plasma ACTH similar to those observed in the 21-day-old and adult rats. Although plasma ACTH levels increased by 84-127% in the 1- and 2-day-old rats, these increases were significantly less than those of rats at all other ages tested. Thus the newborn rat mounts an effective corticosterone response to endotoxin, loses this ability between ages 5-14 days, and regains this response at 21 days of age. Because the hyporesponsive ages exhibit a marked increase in ACTH secretion, the loss of the adrenocortical response to endotoxin appears to be a result of a depressed responsiveness of the adrenal cortex to ACTH.

In utero exposure of high-dose di-n-butyl phthalate resulted in opposite effects on testicular cell apoptosis in late embryonic and pubertal male rat offspring

2017 ◽  
Vol 36 (12) ◽  
pp. 1236-1247 ◽  
Author(s):  
H Shen ◽  
K Liao ◽  
H-F Wu ◽  
H-C Lu ◽  
Y Li ◽  
...  
Keyword(s):  
Western Blot ◽  
Cell Apoptosis ◽  
In Utero ◽  
Male Rat ◽  
In Utero Exposure ◽  
High Dose ◽  
Testicular Cell ◽  
Rat Testis ◽  
Rat Offspring ◽  
Butyl Phthalate

Objective: To investigate the effects of in utero exposure to high-dose di- n-butyl phthalate (DBP) on testicular cell apoptosis in late embryonic and pubertal male rat offspring. Methods: Twenty pregnant Sprague-Dawley (SD) rats were divided into two groups. During gestation day (GD) 12 to GD 19, control group was given 1 ml day−1 of olive oil and experimental group was given DBP 500 mg kg−1 day−1 by gavage. On GD 19.5 and postnatal day (PND) 45, the testes were removed. Morphological analysis of the testes was observed by transmission electron microscopy and hematoxylin and eosin (H&E) staining. Testicular cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). The expression of Bcl-2, Bax, and p53 was presented by immunohistochemistry (IHC) and western blot. Data of the two groups was compared using independent samples t-test and Mann–Whitney test by SPSS 20.0. Results: H&E staining showed that spermatogenetic cells were significantly decreased in DBP exposed pubertal rat testis. The apoptosis index of testes in DBP-treated group was significantly lower on GD 19.5 but higher on PND 45 than that of the controls ( p < 0.01). IHC and western blot revealed significantly increased expression of Bcl-2 in GD 19.5 rat testis and Bax and p53 in PND 45 rat testis after DBP exposure, compared with the control ( p < 0.05). Conclusion: In utero exposure of high-dose DBP resulted in opposite effects on testicular cell apoptosis in late embryonic and pubertal rat offspring. The overexpression of Bcl-2, Bax, and p53 might be related to the occurrence of abnormal apoptosis and finally produce male infertility.

Detection of chondroitin sulfates and decorin in developing fetal and neonatal rat lung

2002 ◽  
Vol 282 (3) ◽  
pp. L484-L490 ◽  
Author(s):  
Yiqiong Wang ◽  
Kaori Sakamoto ◽  
Jody Khosla ◽  
Philip L. Sannes
Keyword(s):  
Extracellular Matrix ◽  
Chondroitin Sulfate ◽  
Wide Distribution ◽  
Neonatal Rat ◽  
Chondroitin Sulfate Proteoglycan ◽  
Sulfate Proteoglycan ◽  
Rat Lung ◽  
Adult Rats ◽  
Chondroitin Sulfates ◽  
Monospecific Antibodies

Chondroitin sulfates and their related proteoglycans are components of extracellular matrix that act as key determinants of growth and differentiation characteristics of developing lungs. Changes in their immunohistochemical distribution during progressive organ maturation were examined with monospecific antibodies to chondroitin sulfate, a nonbasement membrane chondroitin sulfate proteoglycan, and the specific chondroitin sulfate-containing proteoglycan decorin in whole fetuses and lungs from newborn and adult rats. Alveolar and airway extracellular matrix immunostained heavily in the prenatal rat for both chondroitin sulfate and chondroitin sulfate proteoglycan, whereas decorin was confined to developing airways and vessels. These sites retained their respective levels of reactivity with all antibodies through 1–10 days postnatal but thereafter became progressively more diminished and focal in alveolar regions. The heavy staining seen early in development was interpreted to reflect a significant and wide distribution of chondroitin sulfates, chondroitin sulfate proteoglycans, and decorin in rapidly growing tissues, whereas the reduced and more focal reactivity observed at later time points coincided with known focal patterns of localization of fibrillar elements of the extracellular matrix and a more differentiated state.

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