Specific Properties of Heavy Fraction of Mitochondria from Human-term Placenta – Glycerophosphate-dependent Hydrogen Peroxide Production

Honzík, Tomáš; Drahota, Z; Böhm, M.; Ješina, Pavel; Mrácˇek, T.; Paul, Jan; Zeman, Jiřı́; Houštěk, J

doi:10.1016/j.placenta.2005.03.010

Cited by 16 publications

(9 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The placenta has the capacity to oxidize fatty acids (61) and may switch from glucose metabolism to fatty acid metabolism during glucose deprivation. The capacity of placental mitochondria to generate oxidative energy has been suggested to be low (21), but this has later been questioned and it has been proposed that the mitochondria in the placenta are capable of regular ATP production (22), implicating amino acids as another source of ATP during glucose starvation. Thus, the mechanism linking hypoglycemia to mTOR inhibition in cultured primary human trophoblast cells remains to be established.…”

Section: Discussionmentioning

confidence: 99%

Regulation of amino acid transporters by glucose and growth factors in cultured primary human trophoblast cells is mediated by mTOR signaling

Roos

Lagerlöf

Wennergren

et al. 2009

American Journal of Physiology-Cell Physiology

146

147

View full text Add to dashboard Cite

Inhibition of mammalian target of rapamycin (mTOR) signaling in cultured human primary trophoblast cells reduces the activity of key placental amino acid transporters. However, the upstream regulators of placental mTOR are unknown. We hypothesized that glucose, insulin, and IGF-I regulate placental amino acid transporters by inducing changes in mTOR signaling. Primary human trophoblast cells were cultured for 24 h with media containing various glucose concentrations, insulin, or IGF-I, with or without the mTOR inhibitor rapamycin, and, subsequently, the activity of system A, system L, and taurine (TAUT) transporters was measured. Glucose deprivation (0.5 mM glucose) did not significantly affect Thr172-AMP-activated protein kinase phosphorylation or REDD1 expression but decreased S6 kinase 1 phosphorylation at Thr389. The activity of system L decreased in a dose-dependent manner in response to decreasing glucose concentrations. This effect was abolished in the presence of rapamycin. Glucose deprivation had two opposing effects on system A activity: 1) an "adaptive" upregulation mediated by an mTOR-independent mechanism and 2) downregulation by an mTOR-dependent mechanism. TAUT activity was increased after incubating cells with glucose-deprived media, and this effect was largely independent of mTOR signaling. Insulin and IGF-I increased system A activity and insulin stimulated system L activity, effects that were abolished by rapamycin. We conclude that the mTOR pathway represents an important intracellular regulatory link between nutrient and growth factor concentrations and amino acid transport in the human placenta.

show abstract

Section: Discussionmentioning

confidence: 99%

Regulation of amino acid transporters by glucose and growth factors in cultured primary human trophoblast cells is mediated by mTOR signaling

Roos

Lagerlöf

Wennergren

et al. 2009

American Journal of Physiology-Cell Physiology

146

147

View full text Add to dashboard Cite

show abstract

“…Most authors agree that the major sites of superoxide production in mitochondria are complexes I and III of the electron transport chain; however, mGPDH could be another complex where the leak of electrons may occur 29. mGPDH over‐expression has been detected in placenta 35 and in prostate cancer cells 36, suggesting that this protein represents a ROS source participating in induction of oxidative stress. In our study, mRNA analysis has shown several MMA patients with elevated mGPDH mRNA level correlated with high ROS production.…”

Section: Discussionmentioning

confidence: 99%

Methylmalonic acidaemia leads to increased production of reactive oxygen species and induction of apoptosis through the mitochondrial/caspase pathway

Richard

Alvarez-Barrientos

Pérez

et al. 2007

The Journal of Pathology

View full text Add to dashboard Cite

Methylmalonic acidaemia (MMA) is a heterogeneous group of rare genetic metabolic disorders caused by defects related to intracellular cobalamin (vitamin B(12)) metabolism. Increasing evidence has emerged suggesting that free radical generation is involved in the pathophysiology of neurodegenerative diseases, including some inborn errors of metabolism. We have previously identified in MMA patients several differentially expressed proteins involved in oxidative stress [mitochondrial superoxide dismutase (MnSOD) and mitochondrial glycerophosphate dehydrogenase (mGPDH)] and apoptosis by a proteomic approach. We have now extensively evaluated various parameters related to oxidative stress and apoptosis in cultured fibroblasts from a spectrum of patients with methylmalonic acidaemia. Fibroblasts from several MMA patients showed a significant increase in intracellular reactive oxygen species (ROS) content and in MnSOD expression level with respect to controls, suggesting a cellular response to intrinsic ROS stress. Moreover, we have demonstrated, using siRNA, that mGPDH is an important ROS generator in MMA patients. Cells from patients with MMA had a higher rate of apoptosis than those of controls and there was evidence that this process primarily involves the mitochondrial/caspase-dependent pathway. ROS level-phenotype correlation revealed that patients with severe neonatal cblB disorder had elevated intracellular ROS content. These findings support the possible role of oxidative stress in the pathophysiology of methylmalonic acidaemia.

show abstract

“…The molecular basis of GPD2 involvement in sperm capacitation is still unclear, but it may be related to its ability to catalyze the conversion of G3P to DHAP and the simultaneous generation of ROS as demonstrated in brown fat (Drahota et al, 2002, 2003), rat liver (Jesina et al, 2004), human placenta (Honzík et al, 2006), and prostate cancer cell lines (Chowdhury et al, 2005). In spermatozoa, ROS is known to promote hyperactivation and capacitation (Aitken et al, 1995; Leclerc et al, 1997; Ford, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…This shuttle works in parallel with the malate‐aspartate pathway and both are crucial for maintaining the redox balance across the cytoplasm and mitochondria (Eto et al, 1999). GPD2 has also been demonstrated to be involved in ROS generation in brown fat (Drahota et al, 2002, 2003), rat liver (Jesina et al, 2004), human placenta (Honzík et al, 2006) and prostate cancer cell lines (Chowdhury et al, 2005). The GPD2 activity is very high in cauda epididymal spermatozoa of rat and hamster (Schenkman et al, 1965; Weitzel et al, 2000; Kota et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Role of glycerol-3-phosphate dehydrogenase 2 in mouse sperm capacitation

et al. 2010

View full text Add to dashboard Cite

A tyrosine phosphoproteome study of hamster spermatozoa indicated that glycerol-3-phosphate dehydrogenase 2 (GPD2), is one of the proteins that enables tyrosine phosphorylation during sperm capacitation. Further, enzymatic activity of GPD2 correlated positively with sperm capacitation [Kota et al., 2009; Proteomics 9:1809-1826]. Therefore, understanding the function of GPD2 would help to unravel the molecular mechanism of sperm capacitation. In this study, involving the use of spermatozoa from Gpd2(+/+) and Gpd2(-/-) mice, it has been demonstrated that in the absence of Gpd2, hyperactivation and acrosome reaction were significantly altered, and a few changes in protein tyrosine phosphorylation were also observed during capacitation. Evidence is provided to demonstrate that GPD2 activity is required for ROS generation in mouse spermatozoa during capacitation, failing which, capacitation is impaired. These results imply that GPD2 is involved in sperm capacitation.

show abstract

Specific Properties of Heavy Fraction of Mitochondria from Human-term Placenta – Glycerophosphate-dependent Hydrogen Peroxide Production

Cited by 16 publications

References 45 publications

Regulation of amino acid transporters by glucose and growth factors in cultured primary human trophoblast cells is mediated by mTOR signaling

Regulation of amino acid transporters by glucose and growth factors in cultured primary human trophoblast cells is mediated by mTOR signaling

Methylmalonic acidaemia leads to increased production of reactive oxygen species and induction of apoptosis through the mitochondrial/caspase pathway

Role of glycerol-3-phosphate dehydrogenase 2 in mouse sperm capacitation

Contact Info

Product

Resources

About