APC Signal Transduction in Acute Injury Image Long Description

Overview

The APC-EPCR axis protects the heart from ischemic insults caused by ischemia and reperfusion (I/R), the metabolomics was performed in myocardium of young/aged-C57BL/6 mice heart under physiological or pathological conditions with or without APC. The amino acid reservoir plays an important role in movements of skeletal and heart muscles. The downregulation of amino acid metabolism in aging could impair resistance to ischemic insults. The carbohydrate related pathways, such as glutamate metabolism, mitochondrial electron transport chain, starch and sucrose metabolism, and amino sugar metabolism, are all downregulated during ischemic conditions in adult heart. However, there are upregulations in fatty acid metabolism and glycolysis besides the alterations in carbohydrate metabolism in cardiac aging. Therefore, an adaptive metabolic response to ischemic stress in the mouse heart could be impaired in aging.

Presentation

Four images contain the following:

Top left

Immunofluorescent image of cardiac muscle with green and red dots throughout. Legend at the bottom right has the labels APC in green and EPCR in red.

Top right

Light pink line representing a membrane has mirror images on each end of the following:

• A thick light blue entry point with a down arrow in the middle. Above the entry is a dark blue hexagon labeled Glucose.
• Label of EPCR: A light blue line with a semicircle on top. There is one on the left and two on the right. Next to the blue line on the left is a gray line without a semicircle.
• Above each EPCR is a red oblong curved object. The two on the left are labeled APC and the two on the right are labeled Recombinant APC. The second APC on the left is partially faded.
• In the center of the membrane is an undulating green object with a tendril on the top left labeled R46 and a tendril on the bottom right labeled PAR1. Red arrows from each side of the green object point from the APCs down to it. Below the green object are mirror images of a bent black arrow pointing to an oval labeled GLUT4 with two thick blue entry points and a bent arrow pointing back up to a glucose entry point on the membrane.
• Below this is a wide dark blue arrow pointing to a green rounded rectangle label that says Substrate metabolism reprogramming. 

Bottom left

There are two graphs with the following information:

Bar graph

Bar graph entitled APC vs. Vehicle with the words Aged I/R to the right. A black line is under both terms.

The Y-axis is in two parts with the label Down in blue on the top half and the label Up in red on the bottom half. Next to the Y-axis are 10 bars of varying lengths and shades of red to orange labeled as follows:

• Glycolysis (red)
• Pentose Phosphate Pathway (red)
• Aspartate Metabolism (red)
• Oxidation of Branched Chain Fatty Acids (red)
• Warburg Effect (medium orange)
• Biotin Metabolism (light orange)
• Fructose and Mannose Degradation (red)
• Amino Sugar Metabolism (red)
• Glycine and Serine Metabolism (red)
• Citrate Cycle (dark orange)

Each bar from shortest to longest is as follows: Biotin Metabolism, Warburg Effect, Aspartate Metabolism and Oxidation of Branched Chain Fatty Acids (same length), Glycine and Serine Metabolism, Pentose Phosphate Pathway, Glycolysis, Amino Sugar Metabolism, and Fructose and Mannose Degradation.

Next to the bar is a vertical color scale with a gradient going from red at the top with a label of 4e-02 to orange at the center with a label of 2e-01 to pale yellow at the bottom with a label of 4e-01.

Next to the vertical scale is a row of three gray circles going from smallest to largest with the label of Log2(pval) scale above it. Below the circles is a horizontal color scale with a gradient going from green to red with the label Log2FC above it and a number range of -2 to 2 below it. 

Plot graph

Below the bar graph is a plot graph with blue lines and dots with these colors:

• Green: D-Glucose 6-phosphate; L-Lysine; D-Aspartate; L-Threonine
• Pink: D-Fructose 1,6-bisphosphate
• Mauve: D-Glucosamine 6-phosphate
• Taupe: Betaine
• Gray: Creatine
• Blue: D-Fructose 6-phosphate; N6-(L-1,3-Dicarboxypropyl)-L-lysine; L-Glutamine; L-Glutamate; beta-Citryl-L-glutamate; Citrate; Oxaloacetate; Glutathione; Glycine; Sarcosine; Guanidinoacetate; Sarcosine; N,N-Dimethyglycine

Plot structure:

• Top left: Branching out from D-Fructose 6-phosphate is D-Glucose 6-phosphate to the north-northwest; D-Fructose 1,6-bisphosphate to the northwest; and D-Glucosamine 6-phosphate to the southwest. D-Glucosamine 6-phosphate connects to L-Glutamine going east-southeast. L-Glutamine connects to L-Glutamate going east-northeast. L-Glutamate connects to N6-(L-1,3-Dicarboxypropyl)-L-lysine going north-northeast. N6-(L-1,3-Dicarboxypropyl)-L-lysine connects to L-Lysine going north.
• Top right: The following dots connect back to L-Glutamate going southwest in a line: D-Aspartate, Oxaloacetate, Citrate, and beta-Citryl-L-glutamate.
• Bottom: L-Glutamate connects to Glutathione going southeast. Glutathione connects to Glycine going southwest. Glycine branches off three ways:
• West-southwest to L-Threonine
• South-southwest to Guanidinoacetate, which has two branches – Creatine to the southwest and L-Arginine to the south-southeast.
• Linear connection to the southeast in this order: Sarcosine; N,N-Dimethyglycine; Betaine.
• A dashed line connects D-Fructose 6-phosphate to L-Glutamate, and then from L-Glutamate to Glycine.

Bottom right

A vertical color scale with a gradient going from blue to white to red has a range below it of -2.00 on the blue end to the left to 0.00 at the white center to 2.00 on the red end on the right.

Below the color scale is a chart of four columns of dots with colors ranging from blue to white to red. The columns are labeled yirvsysham, airvsasham, yirapcvsyir and airapcvsair, respectively. Each row of four dots is next to the name of an acid or chemical compound. Both the columns of dots and list of acids and compounds is labeled id. The list of acids and compounds is as follows:

• UDP-GALC NAC
• Tartaric acid
• N-Acetyl-alpha-D-glucosamine 1-phosphate
• N-Acetylornithine
• Tyrosine
• Thiamine
• Cytidine
• lsocitrate
• Benzoic acid
• Uridine
• CMP
• Fumarate
• cis-Aconitate
• ltaconic acid
• Glutamine
• 2-Phenylglycine
• L-alpha-Amino-n-butyric acid
• Glutamic acid
• Urea
• Creatine
• Eicosapentaenoic acid (EPA)
• Ecgonine
• Carnosine
• D-Furctose-1-Phosphate
• Citrate
• 2-Phosphoglycerate (2PG)
• 6-Phosphogluconate (6PG)
• D-Glucose-6-Phosphate (G6P)
• D-Fructose-6-Phosphate (F6P)
• Fructose
• Glucose
• D-Glucosamine-6-phosphate
• lnosine-5'-monophosphate (IMP)
• Adonitol
• 3-Phosphoglycerate (3PG)
• cAMP(3'5')