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Alterations in left ventricular function during intermittent hypoxia: Possible involvement of O-GlcNAc protein and MAPK signaling.

Guo X, Shang J, Deng Y, Yuan X, Zhu D, Liu H - Int. J. Mol. Med. (2015)

Bottom Line: IH induced a significant increase in blood pressure, associated with a gradually abnormal myocardial architecture.In parallel, compared with exposure to normoxia, 4 weeks of IH augmented the O-GlcNAc protein, OGT, phosphorylated ERK1/2 and p38 MAPK levels, accompanied by a decrease in OGA levels and an increase in the levels of myocardial nuclear factor-κB (NF-κB), inflammatory cytokines, caspase-3 and cardiomyocyte apoptosis.Taken together, our suggest a possible involvement of O-GlcNAc protein and MAPK signaling in the alterations of left ventricular function and cardiac injury following IH.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, Key Laboratory of Respiratory Disease of the Ministry of Health, Wuhan 430030, P.R. China.

ABSTRACT
Obstructive sleep apnea, characterized by recurrent episodes of hypoxia [intermittent hypoxia (IH)], has been identified as a risk factor for cardiovascular diseases. The O-linked β-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) of proteins has important regulatory implications on the pathophysiology of cardiovascular disorders. In this study, we examined the role of O-GlcNAcylation in cardiac architecture and left ventricular function following IH. Rats were randomly assigned to a normoxia and IH group (2 min 21% O2; 2 min 6-8% O2). Left ventricular function, myocardial morphology and the levels of signaling molecules were then measured. IH induced a significant increase in blood pressure, associated with a gradually abnormal myocardial architecture. The rats exposed to 2 or 3 weeks of IH presented with augmented left ventricular systolic and diastolic function, which declined at week 4. Consistently, the O-GlcNAc protein and O-GlcNAcase (OGA) levels in the left ventricular tissues steadily increased following IH, reaching peak levels at week 3. The O-GlcNAc transferase (OGT), extracellular signal-regulated kinase 1/2 (ERK1/2) and the p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation levels were affected in an opposite manner. The phosphorylation of calcium/calmodulin-dependent protein kinase II (CaMKII) remained unaltered. In parallel, compared with exposure to normoxia, 4 weeks of IH augmented the O-GlcNAc protein, OGT, phosphorylated ERK1/2 and p38 MAPK levels, accompanied by a decrease in OGA levels and an increase in the levels of myocardial nuclear factor-κB (NF-κB), inflammatory cytokines, caspase-3 and cardiomyocyte apoptosis. Taken together, our suggest a possible involvement of O-GlcNAc protein and MAPK signaling in the alterations of left ventricular function and cardiac injury following IH.

No MeSH data available.


Related in: MedlinePlus

Changes in the protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc), O-GlcNAcase (OGA), O-GlcNAc transferase (OGT), extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (p38 MAPK) over the course of 4 weeks of exposure to intermittent hypoxia (IH). (A) Protein O-GlcNAc and OGA levels steadily increased following exposure to IH, reaching peak levels at week 3. The expression levels of OGT and the phosphorylation levels of ERK1/2 and p38 MAPK changed in an opposite manner. The levels of phosphorylated CaMKII remained almost unaltered. (B) Compared with exposure to normoxia (CON), 4 weeks of exposure to IH (CIH) augmented O-GlcNAc protein, OGT, phosphorylated ERK1/2 and p38 MAPK levels, accompanied by a decrease OGA in levels. Data are the means ± SD. *P<0.05 between respective groups.
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f4-ijmm-36-01-0150: Changes in the protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc), O-GlcNAcase (OGA), O-GlcNAc transferase (OGT), extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (p38 MAPK) over the course of 4 weeks of exposure to intermittent hypoxia (IH). (A) Protein O-GlcNAc and OGA levels steadily increased following exposure to IH, reaching peak levels at week 3. The expression levels of OGT and the phosphorylation levels of ERK1/2 and p38 MAPK changed in an opposite manner. The levels of phosphorylated CaMKII remained almost unaltered. (B) Compared with exposure to normoxia (CON), 4 weeks of exposure to IH (CIH) augmented O-GlcNAc protein, OGT, phosphorylated ERK1/2 and p38 MAPK levels, accompanied by a decrease OGA in levels. Data are the means ± SD. *P<0.05 between respective groups.

Mentions: The protein levels of O-GlcNAc in the LV tissues steadily increased following exposure to IH, reaching peak levels at week 3. There was a similar change observed in the OGA levels. The OGT, ERK1/2 and p38 MAPK phosphorylation levels were affected in an opposite manner. The levels of phosphorylated CaMKII remained almost unaltered during the same observation period. In parallel, compared with exposure to normoxia, 4 weeks of exposure to IH augmented the O-GlcNAc protein, OGT, phosphorylated ERK1/2 and p38 MAPK levels, accompanied by a decrease in OGA levels and an increase in cardiomyocyte apoptosis, as well as an increase in the levels of caspase-3, NF-κB p65, TNF-α and IL-6 in the LV tissues (Figs. 3 and 4).


Alterations in left ventricular function during intermittent hypoxia: Possible involvement of O-GlcNAc protein and MAPK signaling.

Guo X, Shang J, Deng Y, Yuan X, Zhu D, Liu H - Int. J. Mol. Med. (2015)

Changes in the protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc), O-GlcNAcase (OGA), O-GlcNAc transferase (OGT), extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (p38 MAPK) over the course of 4 weeks of exposure to intermittent hypoxia (IH). (A) Protein O-GlcNAc and OGA levels steadily increased following exposure to IH, reaching peak levels at week 3. The expression levels of OGT and the phosphorylation levels of ERK1/2 and p38 MAPK changed in an opposite manner. The levels of phosphorylated CaMKII remained almost unaltered. (B) Compared with exposure to normoxia (CON), 4 weeks of exposure to IH (CIH) augmented O-GlcNAc protein, OGT, phosphorylated ERK1/2 and p38 MAPK levels, accompanied by a decrease OGA in levels. Data are the means ± SD. *P<0.05 between respective groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494595&req=5

f4-ijmm-36-01-0150: Changes in the protein levels of O-linked β-N-acetylglucosamine (O-GlcNAc), O-GlcNAcase (OGA), O-GlcNAc transferase (OGT), extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (p38 MAPK) over the course of 4 weeks of exposure to intermittent hypoxia (IH). (A) Protein O-GlcNAc and OGA levels steadily increased following exposure to IH, reaching peak levels at week 3. The expression levels of OGT and the phosphorylation levels of ERK1/2 and p38 MAPK changed in an opposite manner. The levels of phosphorylated CaMKII remained almost unaltered. (B) Compared with exposure to normoxia (CON), 4 weeks of exposure to IH (CIH) augmented O-GlcNAc protein, OGT, phosphorylated ERK1/2 and p38 MAPK levels, accompanied by a decrease OGA in levels. Data are the means ± SD. *P<0.05 between respective groups.
Mentions: The protein levels of O-GlcNAc in the LV tissues steadily increased following exposure to IH, reaching peak levels at week 3. There was a similar change observed in the OGA levels. The OGT, ERK1/2 and p38 MAPK phosphorylation levels were affected in an opposite manner. The levels of phosphorylated CaMKII remained almost unaltered during the same observation period. In parallel, compared with exposure to normoxia, 4 weeks of exposure to IH augmented the O-GlcNAc protein, OGT, phosphorylated ERK1/2 and p38 MAPK levels, accompanied by a decrease in OGA levels and an increase in cardiomyocyte apoptosis, as well as an increase in the levels of caspase-3, NF-κB p65, TNF-α and IL-6 in the LV tissues (Figs. 3 and 4).

Bottom Line: IH induced a significant increase in blood pressure, associated with a gradually abnormal myocardial architecture.In parallel, compared with exposure to normoxia, 4 weeks of IH augmented the O-GlcNAc protein, OGT, phosphorylated ERK1/2 and p38 MAPK levels, accompanied by a decrease in OGA levels and an increase in the levels of myocardial nuclear factor-κB (NF-κB), inflammatory cytokines, caspase-3 and cardiomyocyte apoptosis.Taken together, our suggest a possible involvement of O-GlcNAc protein and MAPK signaling in the alterations of left ventricular function and cardiac injury following IH.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, Key Laboratory of Respiratory Disease of the Ministry of Health, Wuhan 430030, P.R. China.

ABSTRACT
Obstructive sleep apnea, characterized by recurrent episodes of hypoxia [intermittent hypoxia (IH)], has been identified as a risk factor for cardiovascular diseases. The O-linked β-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) of proteins has important regulatory implications on the pathophysiology of cardiovascular disorders. In this study, we examined the role of O-GlcNAcylation in cardiac architecture and left ventricular function following IH. Rats were randomly assigned to a normoxia and IH group (2 min 21% O2; 2 min 6-8% O2). Left ventricular function, myocardial morphology and the levels of signaling molecules were then measured. IH induced a significant increase in blood pressure, associated with a gradually abnormal myocardial architecture. The rats exposed to 2 or 3 weeks of IH presented with augmented left ventricular systolic and diastolic function, which declined at week 4. Consistently, the O-GlcNAc protein and O-GlcNAcase (OGA) levels in the left ventricular tissues steadily increased following IH, reaching peak levels at week 3. The O-GlcNAc transferase (OGT), extracellular signal-regulated kinase 1/2 (ERK1/2) and the p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation levels were affected in an opposite manner. The phosphorylation of calcium/calmodulin-dependent protein kinase II (CaMKII) remained unaltered. In parallel, compared with exposure to normoxia, 4 weeks of IH augmented the O-GlcNAc protein, OGT, phosphorylated ERK1/2 and p38 MAPK levels, accompanied by a decrease in OGA levels and an increase in the levels of myocardial nuclear factor-κB (NF-κB), inflammatory cytokines, caspase-3 and cardiomyocyte apoptosis. Taken together, our suggest a possible involvement of O-GlcNAc protein and MAPK signaling in the alterations of left ventricular function and cardiac injury following IH.

No MeSH data available.


Related in: MedlinePlus