Unknown

Dataset Information

0

Identification of a NF-?B cardioprotective gene program: NF-?B regulation of Hsp70.1 contributes to cardioprotection after permanent coronary occlusion.


ABSTRACT: The transcription factor Nuclear Factor Kappa B (NF-?B) has been shown to be cardioprotective after permanent coronary occlusion (PO) and late ischemic preconditioning (IPC), and yet it is cell injurious after ischemia/reperfusion (I/R) in the heart. There is limited information regarding NF-?B-dependent cardioprotection, and the NF-?B-dependent genes that contribute to the cardioprotection after PO are completely unknown. The objective of the study was to identify NF-?B-dependent genes that contribute to cardioprotection after PO. Microarray analysis was used to delineate genes that potentially contribute to the NF-?B-dependent cardioprotection by determining the overlap between the set of PO regulated genes and genes regulated by NF-?B, using mice with genetic abrogation of NF-?B activation in the heart. This analysis identified 16 genes as candidates for NF-?B-dependent effects after PO. This set of genes overlaps with, but is significantly different from the set of genes we previously identified as regulated by NF-?B after IPC. The genes encoding heat shock protein 70.3 (hspa1a) and heat shock protein 70.1 (hspa1b) were the most significantly regulated genes after PO and were up-regulated by NF-?B. Results using knockout mice show that Hsp70.1 contributes to NF-?B-dependent cardioprotection after PO and likely underlies, at least in part, the NF-??-dependent cardioprotective effect. Our previous results show that Hsp70.1 is injurious after I/R injury. This demonstrates that, like NF-?B itself, Hsp70.1 has antithetical effects on myocardial survival and suggests that this may underlie the similar antithetical effects of NF-?B after different ischemic stimuli. The significance of the research is that understanding the gene network regulated by NF-?B after ischemic insult may lead to identification of therapeutic targets more appropriate for clinical development.

SUBMITTER: Wilhide ME 

PROVIDER: S-EPMC3569977 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

Identification of a NF-κB cardioprotective gene program: NF-κB regulation of Hsp70.1 contributes to cardioprotection after permanent coronary occlusion.

Wilhide Michael E ME   Tranter Michael M   Ren Xiaoping X   Chen Jing J   Sartor Maureen A MA   Medvedovic Mario M   Jones W Keith WK  

Journal of molecular and cellular cardiology 20110323 1


The transcription factor Nuclear Factor Kappa B (NF-κB) has been shown to be cardioprotective after permanent coronary occlusion (PO) and late ischemic preconditioning (IPC), and yet it is cell injurious after ischemia/reperfusion (I/R) in the heart. There is limited information regarding NF-κB-dependent cardioprotection, and the NF-κB-dependent genes that contribute to the cardioprotection after PO are completely unknown. The objective of the study was to identify NF-κB-dependent genes that con  ...[more]

Similar Datasets

| S-EPMC3570030 | biostudies-literature
| S-EPMC7132601 | biostudies-literature
| S-EPMC3075605 | biostudies-other
| S-EPMC3922808 | biostudies-literature
| S-EPMC3778957 | biostudies-literature
| S-EPMC3532050 | biostudies-other
| S-EPMC5357907 | biostudies-literature
| S-EPMC3029248 | biostudies-literature
| S-EPMC3521803 | biostudies-literature
| S-EPMC3193399 | biostudies-other