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

Wen Wang,Ji Wang,Yu Zheng,Fang Lei,Yating Fu,Edward J. Lesnefsky

doi:10.1371/journal.pone.0237643

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.

Highlights

Central chemoreflex is important for regulation of mammalian rhythmic respiratory activity, in which parafacial respiratory group is considered as an important central chemoreceptor [1,2]
We compared the incremental quantity among groups, and we found that the increase in Burst frequency (BF) induced by acidification in preparations from maternal cigarette smoke (CS)-exposed rats was visibly smaller than that from Control rats (P
These results indicate that H2S can attenuate maternal CS exposure-induced impairment of central chemoreception of the offspring, whereas this effect can be hindered by mitoKATP blocker

Summary

Introduction

Central chemoreflex is important for regulation of mammalian rhythmic respiratory activity, in which parafacial respiratory group (pFRG) is considered as an important central chemoreceptor [1,2]. Abnormal prenatal development of pFRG is involved in sudden infant death syndrome and congenital hypoventilation syndrome, whose victims suffer from central. MitoKATP channels and protection of central chemoreception by H2S chemoreflex reduction and central apnea [3,4]. Maternal cigarette smoke (CS) exposure during pregnancy greatly increases the risk of sudden infant death syndrome [5,6]. We have found that maternal CS exposure leads to a deficit in central chemoreception of neonatal rats [7]. The underlying mechanism is not yet being completely understood

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