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Related Concept Videos

Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
Glucagon-like Receptor Agonists01:24

Glucagon-like Receptor Agonists

Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by the...
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Clinical Applications of Epidermal Stem Cells01:19

Clinical Applications of Epidermal Stem Cells

Epidermal stem cells (EpiSCs) are mainly located at the basal layer of the epidermis. These cells repair minor injuries of the skin and replace dead skin cells. However, EpiSCs’ cannot heal severe wounds such as major burns or those from diabetes or hereditary disorders. In such cases, culturing the epidermal stem cells from the patient is possible and has yielded successful treatment options, such as laboratory-grown skin grafts. These grafts are synthesized using a patient’s own EpiSCs...
Cushing Syndrome II: Pathophysiology01:19

Cushing Syndrome II: Pathophysiology

Cortisol production is normally governed by the hypothalamic–pituitary–adrenal (HPA) axis, which maintains hormonal balance through tightly regulated feedback mechanisms. Disruption of this regulatory system is central to the development of Cushing syndrome, whether the excess cortisol originates from external medications or internal pathology. Persistent cortisol elevation alters metabolism, immune function, and endocrine signaling, producing the characteristic clinical features of the...
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GPCR Desensitization

G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...

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Isolation and Differentiation of Stromal Vascular Cells to Beige/Brite Cells
07:22

Isolation and Differentiation of Stromal Vascular Cells to Beige/Brite Cells

Published on: March 28, 2013

Activators of PPARs and LXR decrease the adverse effects of exogenous glucocorticoids on the epidermis.

Marianne Demerjian1, Eung-Ho Choi, Mao-Qiang Man

  • 1Department of Dermatology, UCSF and VA Medical Center, San Francisco, CA 94121, USA.

Experimental Dermatology
|February 25, 2009
PubMed
Summary
This summary is machine-generated.

Glucocorticoids (GC) harm skin by reducing cell growth and differentiation. PPAR and LXR activators applied with GC treatments prevented these toxic effects, protecting epidermal health.

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Isolation and Differentiation of Stromal Vascular Cells to Beige/Brite Cells
07:22

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Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
10:51

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists

Published on: November 15, 2013

Area of Science:

  • Dermatology
  • Molecular Biology
  • Pharmacology

Background:

  • Glucocorticoids (GC) have anti-inflammatory benefits but cause epidermal adverse effects.
  • These include reduced keratinocyte proliferation, differentiation, and barrier homeostasis.
  • Previous attempts using lipid mixtures failed to prevent GC-induced epidermal abnormalities.

Purpose of the Study:

  • To develop strategies preventing topical glucocorticoid (GC) toxicities on the epidermis.
  • To investigate the potential of Peroxisome proliferator-activated receptors (PPAR) and Liver X Receptor (LXR) activators in mitigating GC side effects.

Main Methods:

  • Clobetasol-treated mice were co-treated with various PPAR (alpha, beta/delta, gamma) and LXR activators.
  • Effects on epidermal differentiation markers (involucrin, filaggrin, loricrin) were assessed.
  • Keratinocyte proliferation (PCNA) and skin barrier function were evaluated.

Main Results:

  • PPAR alpha, gamma, and LXR activators prevented decreases in involucrin, filaggrin, and loricrin expression.
  • PPAR alpha, beta/delta, and LXR activators partially prevented reduced keratinocyte proliferation.
  • PPAR gamma and beta/delta activators improved skin barrier homeostasis.

Conclusions:

  • PPAR and LXR activators can prevent multiple adverse effects of topical glucocorticoids on the epidermis.
  • Targeting these pathways offers a promising strategy for managing GC-induced skin toxicity.