Death spreads throughout body

C. elegans

In class discussions, we talk about what happens when the body dies.  And it's always a bit tricky when the discussion gets around to the idea that not every cell dies simultaneously.

And of course, that can lead to a discussion of how tissue death occurs, even in the case of necrosis that occurs as a result of ischemia or other damage. There are certainly many mechanisms involved—quite a few of which have yet to be clarified.

Recently, researchers have brought a step closer by mapping out some of these mechanisms.  In their report (cited below), they reveal that in the gut of the C. elegans worm, calcium ions flowing into cells cause the lysosomes to burst suddenly.  And we know what that means! Intracellular destruction leading to cell death.

What causes the calcium ions to rush into the cells? Gap-junction ion-channel proteins called innexins (analogous to connexins in humans) open up and allow calcium ions to flow into one cell then the next, producing a wave of destruction along the gut.

In interesting phenomenon is that esters of anthranilic acid (formed from the amino acid tryptophan) in the lysosomes not only produce acidosis in the cytosol, they also fluoresce brightly with a bluish glow during this process of cell death.

The video below shows an amazing anterior-to-posterior wave of fluorescent blue in C. elegans worms as this "wave of death" travels along the gut wall.

Okay, now here's the kicker.  By knocking out the innexin channels, the researchers were able to stop the wave of death!  Whoa!  A cure for . . . death?!

Not so fast.  This worked in a WORM, which is not as complex as a vertebrate like the human.  And it only worked in INJURED worms, not elderly worms dying of old age.  So it won't stave off death entirely—or unusually prolong life—but it could lead to treatments for preventing or reducing necrosis that occurs as a result of ischemia and other injuries.

This information—and that dramatic video—could be an interesting addition to your class.  It ties in why it's important to understand concepts such as:

• ions
• amino acids
• ion flow into cells
• gap-junction ion channels
• lysosomes
• cell death and organismal death
• necrosis (and factors leading to necrosis)
• use of animals in research
• the intersection of basic science research and medical applications

Want to know more?

Anthranilate Fluorescence Marks a Calcium-Propagated Necrotic Wave That Promotes Organismal Death in C. elegans. 

• Coburn C, et al.  PLoS Biology 11(7): e1001613. 2013. doi:10.1371/journal.pbio.1001613
• The original research article.  Includes FREE images and PowerPoint slides you can use in your course.
• my-ap.us/19SRjOG

Glowing, Glowing, Gone: Cell Fluorescence Casts Light on How Death Spreads Throughout Body

• By Christopher Crockett. Scientific American online 2 August 2013
• Brief, less technical, article explaining that researchers have identified a key molecular pathway for animal death that may provide clues for better managing traumatic injury and disease in humans.
• my-ap.us/13MxJjs