Related Experiment Video

Updated: Jun 12, 2026

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Expression of active protein phosphatase 1 inhibitor-1 attenuates chronic beta-agonist-induced cardiac apoptosis

Guoli Chen1, Xiaoyang Zhou, Stela Florea

  • 1Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, OH 45267-0575, USA.

Basic Research in Cardiology
|June 1, 2010
PubMed

Insights

Cardiac-specific overexpression of inhibitor-1c reduces apoptosis and heart failure progression. This protective effect involves increased Bcl-2, decreased Bax, and ERK activation, suggesting a novel therapeutic target.

Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • Cellular Mechanisms of Heart Failure

Background:

  • Cardiac apoptosis is a key factor in heart failure development.
  • Protein phosphatase 1 activity, regulated by inhibitor-1 (I-1), is implicated in apoptosis.
  • The role of inhibitor-1c in beta-adrenergic stimulation-induced cardiac apoptosis was unexplored.

Purpose of the Study:

  • To investigate the effects of cardiac-specific overexpression of constitutively active inhibitor-1 (I-1c) on apoptosis and heart failure.
  • To determine the molecular mechanisms underlying I-1c's potential cardioprotective effects.

Main Methods:

  • Cardiac-specific overexpression of I-1c in a mouse model.
  • Induction of cardiac stress using prolonged isoproterenol (ISO) stimulation.
  • Assessment of apoptosis via nuclear condensation, TUNEL staining, and DNA fragmentation.
  • Analysis of apoptotic protein expression (Bcl-2, Bax) and caspase activity.
  • Evaluation of extracellular signal-regulated kinase (ERK) activation.

Main Results:

  • I-1c expression significantly reduced ISO-induced cardiac apoptosis.
  • Beneficial effects were linked to increased anti-apoptotic Bcl-2 and decreased pro-apoptotic Bax.
  • Reduced levels of active caspases and enhanced ERK activation were observed.
  • These changes suggest I-1c confers cardioprotection against beta-adrenergic stress.

Conclusions:

  • Cardiac-specific I-1c overexpression protects against apoptosis induced by prolonged beta-adrenergic stimulation.
  • Mitochondrial signaling and ERK activation pathways are likely involved in I-1c's cardioprotective action.
  • I-1c represents a potential therapeutic target for heart failure management.

More Related Videos

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes15:43

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes

Published on: January 7, 2013

Related Concept Videos

Heart Failure Drugs: Inhibitors of Renin-Angiotensin System01:26

Heart Failure Drugs: Inhibitors of Renin-Angiotensin System

The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
Antihypertensive Drugs: Action of β1 Blockers01:17

Antihypertensive Drugs: Action of β1 Blockers

β1-receptors are primarily located in the heart and kidneys. In cardiac myocytes, these receptors interact with neurotransmitters released by the sympathetic nervous system during heightened activity or danger. As a result, β1-receptors get activated, initiating a series of biochemical processes. Excessive activation of beta receptors due to chronic stress can abnormally increase heart rate and contractility, resulting in high blood pressure or hypertension. To counteract this, β1-blockers...
Heart Failure Drugs: β-Blockers01:22

Heart Failure Drugs: β-Blockers

β-adrenergic antagonists, commonly known as β-blockers, block the effects of sympathetic neurotransmitters such as noradrenaline (NA) and adrenaline (ADR). They have several beneficial effects in heart failure treatment. They reduce heart rate, the force of contraction, and cardiac muscle relaxation. They also slow the atrial-ventricular conduction rate and raise the threshold for arrhythmias. The concentration of β-blockers determines their effects on bronchodilation, vasodilation, and...
Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors01:30

Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors

Angiotensin-converting enzyme (ACE), a vital component of the renin-angiotensin-aldosterone system, is abundant in lung endothelial cells. ACE converts the inactive decapeptide, angiotensin I, into the active octapeptide, angiotensin II. This potent vasoconstrictor narrows blood vessels, increasing resistance to blood flow and elevating blood pressure. Angiotensin II also stimulates aldosterone production, encouraging kidney cells to reabsorb more sodium and water from urine, thereby increasing...