Fig. 8: Tisp40 is a cardiomyocyte-enriched UPR-associated transcription factor. | Nature Communications

Fig. 8: Tisp40 is a cardiomyocyte-enriched UPR-associated transcription factor.

From: Tisp40 prevents cardiac ischemia/reperfusion injury through the hexosamine biosynthetic pathway in male mice

Fig. 8: Tisp40 is a cardiomyocyte-enriched UPR-associated transcription factor.

a–c NRCMs were stimulated with thapsigargin (THA), tunicamycin (TUN) or dithiothreitol (DIT) for 6 h, and then whole-cell lysates and nuclear lysates from NRCMs were prepared for western blot (n = 6). d To suppress ER stress in NRCMs, 4-phenylbutyric acid (4-PBA) and tauroursodeoxycholic acid sodium salt (TUDCA) were added during sI/R injury. Next, whole-cell lysates and nuclear lysates from NRCMs were prepared for western blot (n = 6). e To inhibit ER stress in mice, 4-PBA or TUDCA was administered by a single intraperitoneal injection 15 min before reperfusion, and then whole-cell lysates together with nuclear lysates from the heart were prepared for western blot (n = 6). f Schematic diagram of the molecular mechanisms underlying Tisp40-regulated cardiac I/R injury. ER membrane-resident Tisp40 in I/R-injured hearts is upregulated and cleaved under ER stress, and then released to the nucleus, where it directly binds to the promoter of GFPT1 and subsequently facilitates HBP flux and protein O-GlcNAcylation, thereby mitigating cardiac I/R injury.

Back to article page