HIF-1α in the heart: Remodeling nucleotide metabolism

Abstract

These studies have examined the effect of hypoxia inducible factor 1α (HIF-1α) on nucleotide metabolism in the ischemic heart using a genetic mouse model with heart-specific and regulated expression of a stable form of HIF-1α. We find that AMP deaminase (AMPD), the entry point of the purine nucleotide cycle (PNC), is induced by HIF-1α at the level of mRNA, protein, and activity. AMP that accumulates during ischemia can be metabolized to adenosine by 5′-nucleotidase or to IMP by AMPD. Consistent with the finding of AMPD induction, adenosine accumulation during ischemia was much attenuated in HIF-1α-expressing hearts. Further investigation of nucleotide salvage enzymes found that hypoxanthine phosphoribosyl transferase (HPRT) is also upregulated in HIF-1α-expressing hearts. Treatment of hearts with an inhibitor of the PNC, hadacidin, hastens the fall of the adenylate energy charge during ischemia and the accumulation of AMP. The results provide new insight into the role of the PNC in heart, especially as it relates to ischemia, and indicate that HIF-1α regulates nucleotide metabolism as a compensatory response to hypoxia.

Adaptive remodeling of skeletal muscle energy metabolism in high-altitude hypoxia: Lessons from AltitudeOmics

“…2C; q Ͻ 0.05), suggesting that this pathway may indeed be favored over conventional oxidative metabolism in hypoxia. Accordingly, the first and rate-limiting enzyme of the PNC, AMP deaminase, is up-regulated by HIF-1␣ (39). Expression of the subsequent PNC reamination enzymes is regulated by c-Myc (40), which complements HIF-1␣ to fine-tune metabolic reprogramming of hypoxic cancer cells (41).…”

Biochemical clinical factors associated with missed abortion independent of maternal age

“…[15] It has also been recognized that the activity of ADA protein is upregulated in mouse hearts overexpressing HIF1a, suggesting a role in oxygen-related homeostatic signaling. [16] Lactate dehydrogenase (LDH) is an enzyme found in nearly all living cells, and is broadly expressed in body tissues including blood cells and heart muscle. The LDH is a valuable biomarker for common injuries and disease based on its release during tissue damage.…”

Main histological parameters to be evaluated in an experimental model of myocardial infarct treated by stem cells on pigs

“…With all this activity, cell survival is more likely (Szade et al., 2015). Thus, stabilization and accumulation of HIF1-α is considered cardioprotective, helping preserve myocardial structure and function (Cheng et al., 2016; Lee et al., 2000; Townley-Tilson, Pi & Xie, 2015; Wu et al., 2015). After 4 weeks of postinfarction evolution, we observed how the presence of ASCs coincided with a greater proportion of cardiomyocytes and Purkinje fibers expressing nuclear HIF1-α with respect to the control group.…”