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The Effect of Growth Hormone Administration on the Regulation of Mitochondrial Apoptosis in-Vivo.

Keane J, Tajouri L, Gray B - Int J Mol Sci (2015)

Bottom Line: Results showed that rhGH significantly decreased Bak protein concentrations compared to placebo samples for up to 8 days post treatment.While cytosolic miRNA expression was not found to be significantly affected by rhGH, measurement of the expression of miR-125b in mitochondrial fractions showed a significant down-regulation eight days post-rhGH administration.These findings suggest that rhGH induces short-term anti-apoptotic effects which may be partially mediated through a novel pathway that alters the concentration of mitochondrially-associated miRNAs.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Health Science and Medicine, Bond University, Gold Coast, Queensland 4227, Australia. james.keane@alumni.bond.edu.au.

ABSTRACT
The purpose of this study was to determine whether recombinant human growth hormone (rhGH) would show any significant effects on the expression of apoptosis regulating proteins in peripheral blood mononuclear cells (PBMCs). Additionally, the potential for post-transcriptional regulation of gene expression by miRNA was assessed in two cellular compartments, the cytosol and the mitochondria. Ten male subjects were subcutaneously injected with either rhGH (1 mg) or saline (0.9%) for seven consecutive days in a double-blinded fashion. Blood sampling was undertaken prior to treatment administration and over a period of three weeks following treatment cessation. Bcl-2 and Bak gene and protein expression levels were measured in PBMCs, while attention was also directed to the expression of miR-181a and miR-125b, known translational inhibitors of Bcl-2 and Bak respectively. Results showed that rhGH significantly decreased Bak protein concentrations compared to placebo samples for up to 8 days post treatment. While cytosolic miRNA expression was not found to be significantly affected by rhGH, measurement of the expression of miR-125b in mitochondrial fractions showed a significant down-regulation eight days post-rhGH administration. These findings suggest that rhGH induces short-term anti-apoptotic effects which may be partially mediated through a novel pathway that alters the concentration of mitochondrially-associated miRNAs.

No MeSH data available.


(A) Protein concentrations of Bak from peripheral blood mononuclear cell (PBMC) mitochondrial extracts in recombinant human growth hormone (rhGH) treated compared to placebo treated samples; (B) Protein concentrations of Bcl-2 from PBMC mitochondrial extracts in rhGH treated compared to placebo treated samples. (*p < 0.05 compared to placebo).
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ijms-16-12753-f001: (A) Protein concentrations of Bak from peripheral blood mononuclear cell (PBMC) mitochondrial extracts in recombinant human growth hormone (rhGH) treated compared to placebo treated samples; (B) Protein concentrations of Bcl-2 from PBMC mitochondrial extracts in rhGH treated compared to placebo treated samples. (*p < 0.05 compared to placebo).

Mentions: The pre-treatment measurements of Bak protein concentrations from mitochondrial fractions in rhGH and placebo groups were not significantly different from each other (Figure 1A). Interestingly, Bak protein concentrations were found to be significantly decreased in rhGH treated samples compared to placebo treated samples for measurements taken 1 day (mean difference ± SEM, 95% confidence intervals, p-values: −1.88 ± 0.75 μg/L, −3.66 to −0.99 μg/L, p ≤ 0.05) and eight days (−2.16 ± 0.91 μg/L, −4.32 to −0.09 μg/L, p ≤ 0.05) post-treatment. However, no significant differences were observed between treatment groups at 15 and 22 days post-treatment. No significant differences were observed in Bcl-2 protein concentrations from mitochondrial fractions between rhGH and placebo treated groups at any time point measured (24 h pre-treatment; 1, 8, 15 and 22 days post treatment) (Figure 1B). Cytosolic Bak and Bcl-2 protein concentrations were also analyzed but were found to fall below the detection limit of both assays and subsequently are not reported in this manuscript.


The Effect of Growth Hormone Administration on the Regulation of Mitochondrial Apoptosis in-Vivo.

Keane J, Tajouri L, Gray B - Int J Mol Sci (2015)

(A) Protein concentrations of Bak from peripheral blood mononuclear cell (PBMC) mitochondrial extracts in recombinant human growth hormone (rhGH) treated compared to placebo treated samples; (B) Protein concentrations of Bcl-2 from PBMC mitochondrial extracts in rhGH treated compared to placebo treated samples. (*p < 0.05 compared to placebo).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4490471&req=5

ijms-16-12753-f001: (A) Protein concentrations of Bak from peripheral blood mononuclear cell (PBMC) mitochondrial extracts in recombinant human growth hormone (rhGH) treated compared to placebo treated samples; (B) Protein concentrations of Bcl-2 from PBMC mitochondrial extracts in rhGH treated compared to placebo treated samples. (*p < 0.05 compared to placebo).
Mentions: The pre-treatment measurements of Bak protein concentrations from mitochondrial fractions in rhGH and placebo groups were not significantly different from each other (Figure 1A). Interestingly, Bak protein concentrations were found to be significantly decreased in rhGH treated samples compared to placebo treated samples for measurements taken 1 day (mean difference ± SEM, 95% confidence intervals, p-values: −1.88 ± 0.75 μg/L, −3.66 to −0.99 μg/L, p ≤ 0.05) and eight days (−2.16 ± 0.91 μg/L, −4.32 to −0.09 μg/L, p ≤ 0.05) post-treatment. However, no significant differences were observed between treatment groups at 15 and 22 days post-treatment. No significant differences were observed in Bcl-2 protein concentrations from mitochondrial fractions between rhGH and placebo treated groups at any time point measured (24 h pre-treatment; 1, 8, 15 and 22 days post treatment) (Figure 1B). Cytosolic Bak and Bcl-2 protein concentrations were also analyzed but were found to fall below the detection limit of both assays and subsequently are not reported in this manuscript.

Bottom Line: Results showed that rhGH significantly decreased Bak protein concentrations compared to placebo samples for up to 8 days post treatment.While cytosolic miRNA expression was not found to be significantly affected by rhGH, measurement of the expression of miR-125b in mitochondrial fractions showed a significant down-regulation eight days post-rhGH administration.These findings suggest that rhGH induces short-term anti-apoptotic effects which may be partially mediated through a novel pathway that alters the concentration of mitochondrially-associated miRNAs.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Health Science and Medicine, Bond University, Gold Coast, Queensland 4227, Australia. james.keane@alumni.bond.edu.au.

ABSTRACT
The purpose of this study was to determine whether recombinant human growth hormone (rhGH) would show any significant effects on the expression of apoptosis regulating proteins in peripheral blood mononuclear cells (PBMCs). Additionally, the potential for post-transcriptional regulation of gene expression by miRNA was assessed in two cellular compartments, the cytosol and the mitochondria. Ten male subjects were subcutaneously injected with either rhGH (1 mg) or saline (0.9%) for seven consecutive days in a double-blinded fashion. Blood sampling was undertaken prior to treatment administration and over a period of three weeks following treatment cessation. Bcl-2 and Bak gene and protein expression levels were measured in PBMCs, while attention was also directed to the expression of miR-181a and miR-125b, known translational inhibitors of Bcl-2 and Bak respectively. Results showed that rhGH significantly decreased Bak protein concentrations compared to placebo samples for up to 8 days post treatment. While cytosolic miRNA expression was not found to be significantly affected by rhGH, measurement of the expression of miR-125b in mitochondrial fractions showed a significant down-regulation eight days post-rhGH administration. These findings suggest that rhGH induces short-term anti-apoptotic effects which may be partially mediated through a novel pathway that alters the concentration of mitochondrially-associated miRNAs.

No MeSH data available.