RBM3 interacts with Raptor to regulate autophagy and protect cardiomyocytes from ischemia-reperfusion-induced injury

Nan Wang1, Limeiting Wang1, Changyan Li1

  • 1Science and Technology Achievement Incubation Center, Kunming Medical University, Kunming, China.

Insights

RNA-binding motif protein RBM3 is upregulated during myocardial infarction. Downregulating RBM3 promotes apoptosis and inhibits autophagy in heart cells, highlighting RBM3

Area of Science:

  • Cardiology
  • Molecular Biology
  • Cell Biology

Background:

  • Acute myocardial infarction (AMI) presents significant global health challenges with unclear post-infarction mechanisms.
  • Identifying novel therapeutic targets for AMI is crucial for improving patient outcomes.
  • RNA-binding motif protein 3 (RBM3) is known for its roles in translation, tumor growth, and neuroprotection, but its function in myocardial infarction is largely unexplored.

Purpose of the Study:

  • To investigate the role and biological effects of RBM3 in the context of myocardial infarction.
  • To determine the impact of RBM3 on cardiomyocyte apoptosis and autophagy under ischemia-reperfusion conditions.
  • To elucidate the molecular mechanisms by which RBM3 influences myocardial injury.

Main Methods:

  • Assessing RBM3 expression levels in ischemia-reperfusion (I/R) models.
  • Manipulating RBM3 expression to observe effects on cardiomyocyte autophagy and apoptosis.
  • Investigating the interaction between RBM3 and Raptor to understand its role in regulating the autophagy pathway.

Main Results:

  • RBM3 expression was significantly increased under I/R conditions.
  • Downregulation of RBM3 led to the inhibition of autophagy and promotion of apoptosis in cardiomyocytes.
  • RBM3 was confirmed to interact with Raptor, modulating the autophagy pathway.

Conclusions:

  • RBM3 plays a protective role against ischemia-reperfusion-induced myocardial apoptosis.
  • The protective effects of RBM3 are mediated through the regulation of the autophagy pathway.
  • RBM3 represents a potential therapeutic target for mitigating myocardial injury following infarction.

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.8K
Cardiomyopathy IV: Restrictive Cardiomyopathy01:29

Cardiomyopathy IV: Restrictive Cardiomyopathy

Restrictive cardiomyopathy (RCM) is a rare heart muscle disease characterized by impaired ventricular filling due to stiffened ventricular walls, leading to significant diastolic dysfunction.EtiologyRestrictive cardiomyopathy can arise from both inherited and acquired diseases, many of which are systemic. It is categorized into four main types: infiltrative, storage, non-infiltrative, and endomyocardial diseases.Infiltrative diseases, such as amyloidosis, lead to RCM by depositing amyloid...
21
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.9K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.9K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.5K