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Complex I dysfunction underlies the glycolytic switch in pulmonary hypertensive smooth muscle cells.

Rafikov R, Sun X, Rafikova O, Louise Meadows M, Desai AA, Khalpey Z, Yuan JX, Fineman JR, Black SM - Redox Biol (2015)

Bottom Line: In particular the role of the respiratory Complexes in the mitochondrial dysfunction associated with PH is unresolved and was the focus of our investigations.We further found that the defect in Complex I activity was due to a loss of Complex I assembly, although the assembly of Complexes II and III were both maintained.Thus, we conclude that loss of Complex I assembly may be involved in the switch of energy metabolism in smooth muscle cells to glycolysis and that maintaining Complex I activity may be a potential therapeutic target for the treatment of PH.

View Article: PubMed Central - PubMed

Affiliation: Division of Translational and Regenerative Medicine, The University of Arizona, Tucson, AZ, USA; Department of Medicine, The University of Arizona, Tucson, AZ, USA. Electronic address: ruslanrafikov@deptofmed.arizona.edu.

No MeSH data available.


Related in: MedlinePlus

Mitochondrial membrane potential is increased in pulmonary arterial smooth muscle cells isolated from rats with pulmonary hypertension. PASMC were pre-incubated with TMRM to polarized mitochondria. Digital images of TMRM fluorescence were obtained using fluorescent microscopy. Representative digital images from PASMC isolated from control and PH rats SMC are shown. Quantification of the fluorescent signal indicates that the mitochondrial membrane potential is increased in PH-PASMC. Data are plotted as mean fluorescence intensity (±SEM). *(p<0.05, N=10).
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f0030: Mitochondrial membrane potential is increased in pulmonary arterial smooth muscle cells isolated from rats with pulmonary hypertension. PASMC were pre-incubated with TMRM to polarized mitochondria. Digital images of TMRM fluorescence were obtained using fluorescent microscopy. Representative digital images from PASMC isolated from control and PH rats SMC are shown. Quantification of the fluorescent signal indicates that the mitochondrial membrane potential is increased in PH-PASMC. Data are plotted as mean fluorescence intensity (±SEM). *(p<0.05, N=10).

Mentions: Our data indicate that PASMC from MCT-treated rats have significantly increased mitochondrial ROS production (Fig. 5). This observation correlates well with our finding of respiratory chain dysregulation in PH rats, as more electrons can escape between Complexes and become trapped in oxygen, potentially increasing superoxide levels in the mitochondria. The mitochondrial membrane potential is also increased in PASMC from MCT-treated rats (Fig. 6). This result is surprising in the context of reduced activity of Complexes I–III, all of which maintain membrane potential, in PASMC from MCT-treated rats.


Complex I dysfunction underlies the glycolytic switch in pulmonary hypertensive smooth muscle cells.

Rafikov R, Sun X, Rafikova O, Louise Meadows M, Desai AA, Khalpey Z, Yuan JX, Fineman JR, Black SM - Redox Biol (2015)

Mitochondrial membrane potential is increased in pulmonary arterial smooth muscle cells isolated from rats with pulmonary hypertension. PASMC were pre-incubated with TMRM to polarized mitochondria. Digital images of TMRM fluorescence were obtained using fluorescent microscopy. Representative digital images from PASMC isolated from control and PH rats SMC are shown. Quantification of the fluorescent signal indicates that the mitochondrial membrane potential is increased in PH-PASMC. Data are plotted as mean fluorescence intensity (±SEM). *(p<0.05, N=10).
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556771&req=5

f0030: Mitochondrial membrane potential is increased in pulmonary arterial smooth muscle cells isolated from rats with pulmonary hypertension. PASMC were pre-incubated with TMRM to polarized mitochondria. Digital images of TMRM fluorescence were obtained using fluorescent microscopy. Representative digital images from PASMC isolated from control and PH rats SMC are shown. Quantification of the fluorescent signal indicates that the mitochondrial membrane potential is increased in PH-PASMC. Data are plotted as mean fluorescence intensity (±SEM). *(p<0.05, N=10).
Mentions: Our data indicate that PASMC from MCT-treated rats have significantly increased mitochondrial ROS production (Fig. 5). This observation correlates well with our finding of respiratory chain dysregulation in PH rats, as more electrons can escape between Complexes and become trapped in oxygen, potentially increasing superoxide levels in the mitochondria. The mitochondrial membrane potential is also increased in PASMC from MCT-treated rats (Fig. 6). This result is surprising in the context of reduced activity of Complexes I–III, all of which maintain membrane potential, in PASMC from MCT-treated rats.

Bottom Line: In particular the role of the respiratory Complexes in the mitochondrial dysfunction associated with PH is unresolved and was the focus of our investigations.We further found that the defect in Complex I activity was due to a loss of Complex I assembly, although the assembly of Complexes II and III were both maintained.Thus, we conclude that loss of Complex I assembly may be involved in the switch of energy metabolism in smooth muscle cells to glycolysis and that maintaining Complex I activity may be a potential therapeutic target for the treatment of PH.

View Article: PubMed Central - PubMed

Affiliation: Division of Translational and Regenerative Medicine, The University of Arizona, Tucson, AZ, USA; Department of Medicine, The University of Arizona, Tucson, AZ, USA. Electronic address: ruslanrafikov@deptofmed.arizona.edu.

No MeSH data available.


Related in: MedlinePlus