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Related Concept Videos

Endoplasmic Reticulum01:39

Endoplasmic Reticulum

106.9K
The Endoplasmic Reticulum (ER) in eukaryotic cells is a substantial network of interconnected membranes with diverse functions, from calcium storage to biomolecule synthesis. A primary component of the endomembrane system, the ER manufactures phospholipids critical for membrane function throughout the cell. Additionally, the two distinct regions of the ER specialize in the manufacture of specific lipids and proteins.
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The Endoplasmic Reticulum01:43

The Endoplasmic Reticulum

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The endoplasmic reticulum or ER makes up for more than half of the membranes in a cell and accounts for 10% of total cell volume. It is also the primary protein and lipid synthesis factory for most cell organelles, such as the Golgi apparatus, lysosomes, secretory vesicles, and the plasma membrane. Despite being the most extensive and functionally complex subcellular organelle, ER was the last to be discovered. After years of deliberation, Keith Porter and George Palade in the year 1954,...
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Smooth Endoplasmic Reticulum01:21

Smooth Endoplasmic Reticulum

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Smooth endoplasmic reticulum or smooth ER is a sub-organelle with specialized functions in animal cells and plant cells. It is often associated with the tubule morphology of the endoplasmic reticulum.
The ER provides optimal conditions for synthesizing steroid hormones and lipids, such as phospholipids and triglycerides. Traditionally, lipid metabolism was considered to be a smooth ER function. However, there is no direct evidence to prove that rough ER is completely excluded from lipid...
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Directing Proteins to the Rough Endoplasmic Reticulum01:34

Directing Proteins to the Rough Endoplasmic Reticulum

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The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
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ATP Synthase: Mechanism01:48

ATP Synthase: Mechanism

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In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...
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ATP Synthase: Structure01:18

ATP Synthase: Structure

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ATP synthase or ATPase is among the most conserved proteins found in bacteria, mammals, and plants. This enzyme can catalyze a forward reaction in response to the electrochemical gradient, producing ATP from ADP and inorganic phosphate. ATP synthase can also work in a reverse direction by hydrolyzing ATP and generating an electrochemical gradient. Different forms of ATP synthases have evolved special features to meet the specific demands of the cell. Based on their specific feature, ATP...
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Related Experiment Video

Updated: Jan 23, 2026

Purification of the Sarco-Endoplasmic Reticulum Ca2+-ATPase from Rabbit Muscle
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Purification of the Sarco-Endoplasmic Reticulum Ca2+-ATPase from Rabbit Muscle

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Sphingomyelin Synthase 2 Promotes Endothelial Dysfunction by Inducing Endoplasmic Reticulum Stress.

Lingyue Hua1, Na Wu2, Ruilin Zhao3

  • 1Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Nanchang University, Nanchang 330006, Jiangxi, China. hly3288551238@163.com.

International Journal of Molecular Sciences
|June 20, 2019
PubMed
Summary

Sphingomyelin synthase 2 (SMS2) promotes endothelial dysfunction (ED) by activating the Wnt/β-catenin pathway and increasing cholesterol, leading to endoplasmic reticulum (ER) stress. Inhibiting ER stress or cholesterol synthesis reduces ED.

Keywords:
atherosclerosisendoplasmic reticulum stressendothelial dysfunctionsphingomyelin synthase 2β-catenin

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Area of Science:

  • Cardiovascular Biology
  • Cellular Stress Response
  • Molecular Mechanisms of Disease

Background:

  • Endothelial dysfunction (ED) is a key factor in atherosclerotic cardiovascular disease.
  • Sphingomyelin synthase 2 (SMS2) has been previously linked to promoting ED.
  • Endoplasmic reticulum (ER) stress is also a known contributor to ED, but its relationship with SMS2 was unclear.

Purpose of the Study:

  • To investigate the correlation between SMS2 and ER stress in endothelial cells.
  • To elucidate the molecular mechanisms linking SMS2, ER stress, and ED.
  • To determine the role of the Wnt/β-catenin pathway and intracellular cholesterol in this process.

Main Methods:

  • Overexpression of SMS2 in human umbilical vein endothelial cells (HUVECs).
  • Treatment with pharmacological agents: 4-PBA (ER stress inhibitor), simvastatin (cholesterol synthesis inhibitor), LiCl, and salinomycin.
  • Analysis of Wnt/β-catenin pathway activation and ER stress markers.

Main Results:

  • SMS2 overexpression promoted lipoprotein receptor-related protein 6 (LRP6) phosphorylation and activated the Wnt/β-catenin pathway.
  • Wnt/β-catenin pathway activation induced ER stress, while its inhibition blocked ER stress.
  • Inhibition of ER stress with 4-PBA reduced ED.
  • Simvastatin-induced reduction in intracellular cholesterol decreased ER stress and ED.

Conclusions:

  • SMS2 activates the Wnt/β-catenin pathway, leading to intracellular cholesterol accumulation.
  • Both Wnt/β-catenin activation and cholesterol accumulation contribute to ER stress induction.
  • SMS2-induced ER stress is a critical mechanism underlying endothelial dysfunction and atherosclerotic cardiovascular disease.