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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) Changes from baseline measurements in the expression of miR-125b miRNA levels from the cytosol of PBMCs in rhGH treated compared to placebo treated samples; (B) Changes from baseline measurements in the expression of miR-181a miRNA levels from the cytosol of PBMCs in rhGH treated compared to placebo treated samples; (C) Changes from baseline measurements in the expression of miR-125b miRNA levels from isolated PBMC mitochondria in rhGH treated compared to placebo treated samples; (D) Changes from baseline measurements in the expression of miR-181a miRNA levels from isolated PBMC mitochondria in rhGH treated compared to placebo treated samples. (*p < 0.05 compared to placebo).
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ijms-16-12753-f003: (A) Changes from baseline measurements in the expression of miR-125b miRNA levels from the cytosol of PBMCs in rhGH treated compared to placebo treated samples; (B) Changes from baseline measurements in the expression of miR-181a miRNA levels from the cytosol of PBMCs in rhGH treated compared to placebo treated samples; (C) Changes from baseline measurements in the expression of miR-125b miRNA levels from isolated PBMC mitochondria in rhGH treated compared to placebo treated samples; (D) Changes from baseline measurements in the expression of miR-181a miRNA levels from isolated PBMC mitochondria in rhGH treated compared to placebo treated samples. (*p < 0.05 compared to placebo).

Mentions: No significant differences were observed in the level of expression of miR-125b from cellular lysate at any time point compared to baseline measurements between rhGH and placebo treated groups (Figure 3A). In addition, expression changes from baseline measurements for miR-181a from cellular lysate were not found to be significantly different between rhGH and placebo treated groups for any of the post-treatment time points (Figure 3B). The change in fold expression of miR-125b in mitochondrial fractions from baseline values was found to be significantly decreased in rhGH treated samples compared to placebo treated controls (−2.86 ± 0.74, −4.61 to −1.11, p ≤ 0.05) at 8 days post-treatment (Figure 3C). However no significant differences were observed between the treatment groups at 1, 15 or 22 days post-treatment. No significant differences were observed in the level of expression of miR-181a from mitochondrial fractions at any time point compared to baseline measurements between rhGH and placebo treated groups (Figure 3D).


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) Changes from baseline measurements in the expression of miR-125b miRNA levels from the cytosol of PBMCs in rhGH treated compared to placebo treated samples; (B) Changes from baseline measurements in the expression of miR-181a miRNA levels from the cytosol of PBMCs in rhGH treated compared to placebo treated samples; (C) Changes from baseline measurements in the expression of miR-125b miRNA levels from isolated PBMC mitochondria in rhGH treated compared to placebo treated samples; (D) Changes from baseline measurements in the expression of miR-181a miRNA levels from isolated PBMC mitochondria 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-f003: (A) Changes from baseline measurements in the expression of miR-125b miRNA levels from the cytosol of PBMCs in rhGH treated compared to placebo treated samples; (B) Changes from baseline measurements in the expression of miR-181a miRNA levels from the cytosol of PBMCs in rhGH treated compared to placebo treated samples; (C) Changes from baseline measurements in the expression of miR-125b miRNA levels from isolated PBMC mitochondria in rhGH treated compared to placebo treated samples; (D) Changes from baseline measurements in the expression of miR-181a miRNA levels from isolated PBMC mitochondria in rhGH treated compared to placebo treated samples. (*p < 0.05 compared to placebo).
Mentions: No significant differences were observed in the level of expression of miR-125b from cellular lysate at any time point compared to baseline measurements between rhGH and placebo treated groups (Figure 3A). In addition, expression changes from baseline measurements for miR-181a from cellular lysate were not found to be significantly different between rhGH and placebo treated groups for any of the post-treatment time points (Figure 3B). The change in fold expression of miR-125b in mitochondrial fractions from baseline values was found to be significantly decreased in rhGH treated samples compared to placebo treated controls (−2.86 ± 0.74, −4.61 to −1.11, p ≤ 0.05) at 8 days post-treatment (Figure 3C). However no significant differences were observed between the treatment groups at 1, 15 or 22 days post-treatment. No significant differences were observed in the level of expression of miR-181a from mitochondrial fractions at any time point compared to baseline measurements between rhGH and placebo treated groups (Figure 3D).

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.