Chondria and traps cells in the G2/M phase of the cell cycle, which slows proliferation

Chondria and traps cells in the G2/M phase of the cell cycle, which slows proliferation and promotes apoptosis [29]. In this study, we demonstrate for the first time that H2S attenuates HG and palmitate-induced HPASMC proliferation by inhibiting mitochondrial fragmentation. Likely, H2S affects mitochondrial dynamics through differential modulation of mitochondrial fission and fusion proteins, which impairs the mitochondrial fusion ission balance because manipulating Drp1 and Mfn2 expression altered the effects of H2S. Several studies show that vascular reactive oxygen production is related to NADPH oxidases, xanthine oxidase,lipoxygenase, and mitochondrial election transport. Considering the ROS-induced cell-proliferation mechanism, a growing body of evidence suggests that ROS play a vital role in activating MAPK and PI3K/Akt cascades mediated by HG [30]. Over the past decade, several investigators have shown that H2O2 and ROS CPI-455 supplier regulate cell proliferation. Transient H2O2 production is considered an intracellular signal for cell growth and transformation triggered by surface receptor activation and determined by mitochondrial metabolic status [31]. Our results showed that HG increased ROS in the mitochondria and cytoplasm, whereas exogenous H2S reduced ROS production.Sun et al. Cell Biosci (2016) 6:Page 13 ofMito-length (nm)Mitochondrial area (1000 nm 2 )S AC al l2000 1500 1000 500ro aH +P nt +N aL +N G Co aL Hol +P al S +P aL +N A C H G on C +N G aH trH+PGFig. 8 Representative mitochondrial morphology in VSMCs observed using electron microscopy (EM). Scale bar at high magnification = 2 . *p < 0.05 vs control, **p < 0.01 vs control, # p < 0.05 vs HG and Pal, and ## p < 0.01 vs HG and PalHThe major observation from this study is that hyperglycemia and high glucose-induced oxidative stress caused mitochondrial fragmentation in VSMCs, which was demonstrated by confocal microscopic imagingand TEM. Because mitochondrial morphology is tightly controlled by the balance between mitochondrial fission and fusion [32]. We postulate that hyperglycemia and high glucose-induced mitochondrial fragmentationH GGH+P aL+PSun et al. Cell Biosci (2016) 6:Page 14 ofFig. 9 Exogenous H2S and Mdivi-1 inhibit mitochondrial fragmentation to reduce proliferation in VSMCs. a Different concentrations of Mdivi-1 affected Drp expression. (n = 4) (**p < 0.01 vs DMSO, ***p < 0.001 vs DMSO). b Increased mitochondrial fragmentation count in VSMCs with the HG and palmitate treatment compared with VSMCs treated with NaHS and Mdivi-1. The results are representative of three independent experiments (*p < 0.05 vs control, # p < 0.05 vs HG and Pal)is caused by enhancing fission and reducing fusion. To support this notion, we used the mitochondria-targeted fluorescent probe mitotracker to demonstrate that mitochondria in high glucose-treated cells were nearly unableto fuse compared with control mitochondria. However, exogenous H2S also inhibited mitochondrial fission and promoted mitochondrial fusion. At the molecular level, we observed that high glucose-triggered ROS activatedSun et al. Cell Biosci (2016) 6:Page 15 ofFig. 10 Silencing Drp1 expression prevents HG-induced ROS production and migration as well as cell proliferative protein expression. a siRNA transfection effectively reduced Drp1 expression. (n = 3) ROS production in the cytoplasm (b) *p < 0.05 vs control, #p < 0.05 vs HG and Pal, and ## p < 0.01 vs HG and PalDrp-1, which was indicated by PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/26100631 a significantly increased a.