Dataset Information

Mitochondrial KATP channels contribute to the protective effects of hydrogen sulfide against impairment of central chemoreception of rat offspring exposed to maternal cigarette smoke.

ABSTRACT: We previously reported that maternal cigarette smoke (CS) exposure resulted in impairment of central chemoreception and induced mitochondrial dysfunction in offspring parafacial respiratory group (pFRG), the kernel for mammalian central chemoreception. We also found that hydrogen sulfide (H2S) could attenuate maternal CS exposure-induced impairment of central chemoreception in the rat offspring in vivo. Mitochondrial ATP sensitive potassium (mitoKATP) channel has been reported to play a significant role in mitochondrial functions and protect against apoptosis in neurons. Thus, we hypothesize here that mitoKATP channel plays a role in the protective effects of H2S on neonatal central chemoreception in maternal CS-exposed rats. Our findings revealed that pretreatment with NaHS (donor of H2S, 22.4mM) reversed the central chemosensitivity decreased by maternal CS exposure, and also inhibited cell apoptosis in offspring pFRG, however, 5-HD (blocker of mitoKATP channels, 19mM) attenuated the protective effects of NaHS. In addition, NaHS declined pro-apoptotic proteins related to mitochondrial pathway apoptosis in CS rat offspring pFRG, such as Bax, Cytochrome C, caspase9 and caspase3. NaHS or 5-HD alone had no significant effect on above indexes. These results suggest that mitoKATP channels play an important role in the protective effect of H2S against impairment of central chemoreception via anti-apoptosis in pFRG of rat offspring exposed to maternal CS.

SUBMITTER: Lei F

PROVIDER: S-EPMC7567348 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Mitochondrial KATP channels contribute to the protective effects of hydrogen sulfide against impairment of central chemoreception of rat offspring exposed to maternal cigarette smoke.

Lei Fang F Wang Wen W Fu Yating Y Wang Ji J Zheng Yu Y

PloS one 20201016 10

We previously reported that maternal cigarette smoke (CS) exposure resulted in impairment of central chemoreception and induced mitochondrial dysfunction in offspring parafacial respiratory group (pFRG), the kernel for mammalian central chemoreception. We also found that hydrogen sulfide (H2S) could attenuate maternal CS exposure-induced impairment of central chemoreception in the rat offspring in vivo. Mitochondrial ATP sensitive potassium (mitoKATP) channel has been reported to play a signific ...[more]

PMID: 33064729

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Project description:In urban areas with a predominance of early to mid-20th century housing stock, islands of children possessing blood lead levels (PbB) in excess of CDC guidelines (>10?g/dL) exist. Many of these children are also exposed to environmental tobacco smoke (ETS). The current study examined the impact of Pb-exposure (PbB levels of 1-55?g/dL) with/without concurrent ETS exposure on immune system function in 318 children aged 6-84 months from the urban area of Springfield-Greene County, MO. In this population, 36.5% of children possessed PbB levels >10?g/dL, 62.9% of children came from smoking homes, 51.9% of children were under 2 years of age, and the population was WIC eligible and predominantly of white, non-Hispanic ethnicity. Multiple immune function markers including cell counts, IgE levels, sCD25 (sIL2R) and IL4 concentrations, and titers to common childhood immunizations were analyzed for correlation with Pb and/or ETS exposure. Increased IgE levels (p<0.01) were found in children with PbB levels within CDC Classes II-IV - this finding was primarily attributable to elevated IgE levels in the subpopulation of children with concurrent Pb and ETS exposure. A trend (0.05<p<0.01) of increases in % total T-cells (p=0.06) was also found in children with concurrent elevated PbB levels and ETS exposure. This trend was not found in the subset of children without ETS exposure nor was it present in the analysis of the entire population set. Conversely, alterations in median values for % lymphocytes, % granulocytes, and % activated T-cells across Pb classes were present in the subpopulation of children expose to Pb alone (without concurrent ETS exposure) though a clear trend was not evident. In the entire population set, a statistically significant correlation between ETS and PbB levels was found. This study indicates that prior reports of a correlation between elevated PbB levels and serum IgE levels may be strongly influenced by exposure to ETS. Findings from this study also indicate that Pb is an immune modulator and PbB levels may be influenced by ETS exposure.

Project description:BACKGROUND:Lung aging is characterized by a number of structural alterations including fibrosis, chronic inflammation and the alteration of inflammatory cell composition. Chronic exposure to cigarette smoke (CS) is known to induce similar alterations and may contribute to premature lung aging. Additionally, aging and CS exposure are associated with transcriptional alterations in the lung. The current work aims to explore the interaction between age- and CS- associated transcriptomic perturbations and develop a transcriptomic clock able to predict the biological age and the impact of external factors on lung aging. RESULTS:Our investigations revealed a substantial overlap between transcriptomic response to CS exposure and age-related transcriptomic alterations in the murine lung. Of particular interest is the strong upregulation of immunoglobulin genes with increased age and in response to CS exposure, indicating an important implication of B-cells in lung inflammation associated with aging and smoking. Furthermore, we used a machine learning approach based on Lasso regression to build a transcriptomic age model that can accurately predict chronological age in untreated mice and the deviations associated with certain exposures. Interestingly, CS-exposed-mice were predicted to be prematurely aged in contrast to mice exposed to fresh air or to heated tobacco products (HTPs). The accelerated aging rate associated with CS was reversed upon smoking cessation or switching to HTPs. Additionally, our model was able to predict premature aging associated with thoracic irradiation from an independent public dataset. CONCLUSIONS:Aging and CS exposure share common transcriptional alteration patterns in the murine lung. The massive upregulation of B-cell restricted genes during these processes shed light on the contribution of cell composition and particularly immune cells to the measured transcriptomic signal. Through machine learning approach, we show that gene expression changes can be used to accurately monitor the biological age and the modulations associated with certain exposures. Our findings also suggest that the premature lung aging is reversible upon the reduction of harmful exposures.

Dataset Information

Mitochondrial KATP channels contribute to the protective effects of hydrogen sulfide against impairment of central chemoreception of rat offspring exposed to maternal cigarette smoke.

Publications

Mitochondrial KATP channels contribute to the protective effects of hydrogen sulfide against impairment of central chemoreception of rat offspring exposed to maternal cigarette smoke.

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