Post‐transcriptional analysis of rat mitochondrial D‐3‐hydroxybutyrate dehydrogenase control through development and physiological stages^*

Abstract

The nuclear encoded mitochondrial D-3-hydroxybutyrate dehydrogenase (BDH) is synthesized in the cytosal as a larger precursor. This membrane enzyme which requires lecithin for activity plays an essential role in energy metabolism as a ketone bodies-converting enzyme. A cDNA clone of the rat liver enzyme encompassing an antigenic determinant peptide has been isolated after immunoscreening of a lambda gt11 expression library. The nucleotide sequence of this 279-base cDNA insert contains a single open reading frame of 93 amino-acids, which represents about a third of the mature enzyme. Amino-acid sequence analysis predicts a hydrophobic stretch of 29 amino-acids long which probably functions as membrane anchor domain, or as an important region for the enzyme activation by phospholipid. By using this cDNA probe the BDH gene has been investigated at the mRNA level. There is only one mRNA (2-kb size) for BDH whatever the studied tissue. The rat gene is differently expressed since its mRNA is already present in the foetus liver while the BDH polypeptide amount is low and its enzymatic activity is not detectable even in the late stage of foetal development. The mRNA content is higher in the liver than in extrahepatic tissues. Adrenalectomy and ovariectomy increase liver mRNA content and polypeptide level, as well as activity of BDH. These effects are totally or partially abolished by corticosterone and estradiol treatments respectively. In addition, a 15-day hyperlipidic diet stimulates BDH gene expression. Present results show that the gene expression of this mitochondrial enzyme is modulated through development and hormonal and metabolic conditions mentioned above.

Mammalian adaptation to extrauterine environment: mitochondrial functional impairment caused by prematurity

“…Premature birth in rat by 1 day could result in altered mitochondrial function in the postnatal period if the tissue pattern of mitochondrial biogenesis (proliferation) is abruptly interrupted. Altered mitochondrial function at this stage of development could be related to abnormal differentiation of pre-existing organelles [4][5][6][7][8][9][10][11][12][13]. To distinguish between these two possibilities, mitochondrial F1-ATPase f8-subunit was assayed in both liver homogenates and isolated mitochondria.…”

“…These parameters were used as indexes of liver mitochondrial abundance (proliferation) and extent of organelle differentiation respectively [6][7][8]. In addition, as nuclear-encoded mitochondrial mRNAs accumulate in liver during fetal development [11][12][13], we determined their content in preterm fetuses.…”

“…The postnatal onset of oxidative phosphorylation in liver mitochondria of term rat neonates is accomplished by the synergistic action of two main processes: (i) a preferential increase in the rate of synthesis of mitochondrial proteins [5,[7][8][9] and (ii} an increase in intramitochondrial adenine nucleotide concentration [3][4][5]10]. The former is accomplished by prenatal accumulation of nuclear-encoded mitochondrial mRNAs [11][12][13], which are efficiently translated immediately after birth [13]. The latter, which is independent of protein synthesis [5,8], promotes coupling efficiency between respiration and oxidative phosphorylation [3][4][5][14][15][16].…”

Urinary protein changes during the short-term growth and development of rats

“…Comparing Day 0 with Day 6, we found that d-3-hydroxybutyrate dehydrogenase 2 was differentially expressed in rat urine under strict screening conditions (FC ≥ 2 or ≤ 0.5, P < 0.01). It has been shown that the regulation of mitochondrial d-3-hydroxybutyrate dehydrogenase can modulate different stages of rat development and physiology [ 17 ]. Moreover, alpha-lactalbumin can improve energy balance and metabolism [ 18 ] and promote the growth and maturation of the small intestine in suckling rats [ 19 ].…”

Hibernation impact on the catalytic activities of the mitochondrial D-3-hydroxybutyrate dehydrogenase in liver and brain tissues of jerboa (Jaculus orientalis)

“…The filters were washed twice at 42°C for 30 min in 2 × SSC, 0.5% SDS and once at 65°c for 30 min in 1 × SSC, 0.1% SDS. Rat BDH cDNA probe was described earlier [34]. Northern blots were normalized with the 18 S and 28 S ribosomal RNAs.…”