How does hypertrophy lead to increased DNA content of a cell?

[whatdidigetinto]

It says in my notes that it happens because the cell arrests in the cell cycle without undergoing mitosis. But what makes it not undergo mitosis?

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[Myxedema]

It's not the DNA content which is increased; the amount of structural proteins (e.g. myosin) and number of organelles are increased.

 

[Kaputt]

Hypertrophy-ing cardiac myocytes can go from 2n to 4n (an increase in DNA content), along with increasing their RNA content and protein synthesis.

Think of it this way: we all know that cardiac myocytes can't divide because they're permanent cells. But when they hypertrophy, they're making their best attempt at it. Their best attempt is to duplicate their DNA content, but the cell doesn't actually divide.

Summary: if you are ever asked the DNA content of hypertrophied cardiac myocytes, pick 4n.

The molecular mechanisms are irrelevant to the level of detail that Step 1 tests. If you really want to dig, look it up in the primary literature.

 

[whatdidigetinto]

Thanks man. That makes so much more sense.

 

[chaotic mind]

the nuclei of hypertrophied cells MAY have a higher DNA content because the cells fail to undergo mitosis.

 

[Myxedema]

Hypertrophy-ing cardiac myocytes can go from 2n to 4n (an increase in DNA content), along with increasing their RNA content and protein synthesis.

Think of it this way: we all know that cardiac myocytes can't divide because they're stable cells. But when they hypertrophy, they're making their best attempt at it. Their best attempt is to duplicate their DNA content, but the cell doesn't actually divide.

Summary: if you are ever asked the DNA content of hypertrophied cardiac myocytes, pick 4n.

The molecular mechanisms are irrelevant to the level of detail that Step 1 tests. If you really want to dig, look it up in the primary literature.

From Robbins Pathologic Basis of Disease, 8th Edition:

Hypertrophy refers to an increase in the size of cells, resulting in an increase in the size of the organ. The hypertrophied organ has no new cells, just larger cells. The increased size of the cells is due to the synthesis of more structural components of the cells. Cells capable of division may respond to stress by undergoing both hyperplasia (described below) and hypertrophy, whereas in nondividing cells (e.g., myocardial fibers) increased tissue mass is due to hypertrophy. In many organs hypertrophy and hyperplasia may coexist and contribute to increased size.

Mechanisms of Hypertrophy

Hypertrophy is the result of increased production of cellular proteins...

Although hypertrophy usually refers to increase in size of cells or tissues, sometimes a subcellular organelle may undergo selective hypertrophy. For instance, individuals treated with drugs such as barbiturates show hypertrophy of the smooth endoplamic reticulum (ER) in hepatocytes, which is an adaptive response that increases the amount of enzymes (cytochrome P-450 mixed function oxidases) available to detoxify the drugs.

There's no mention of DNA replication.

Also, like you've said, muscle cells are permanent cells, i.e. they remain in G0. Since DNA replication takes place in S phase, by that logic, muscle cells would be able to progress into G1 and S from G0. That's contradictory.

 

[chaotic mind]

the nuclei of hypertrophied cells MAY have a higher DNA content because the cells fail to undergo mitosis.

I got that from robbins 7e.
and I also remember seeing it in a number of other resources- class notes etc

 

[Kaputt]

I think the "hypertrophy = 4n" in cardiac myocytes thing is a Goljan pearl. So who knows, he might have made it up.

 

[ProteinTreasure]

Is this process reversible?

 

[Phloston]

I have annotated into p.79 of my FA2012 that while skeletal and cardiac muscle cells are permanent, smooth muscle is stable (quiescent).

I would also like to know more about this supposed tetraploid state for hypertrophying cells. As far as I'm aware, the only cells that naturally enter this state are the primary gametocytes.

However, I found this article on PubMed:

Adv Myocardiol. 1980;1:553-63.
Changes in DNA synthesis in significantly hypertrophied human cardiac muscle.
Yabe Y, Abe H.

Here is the abstract:

To observe changes in nucleic acid synthesis, which represent the major role in cell function, DNA volume was measured for each myocardial cell biopsied from 28 patients that were cineangiographically recognized as hypertrophic cardiomyopathy or congestive cardiomyopathy with the use of Feulgen cytophtometry. Normal heart muscle cell are diploid to tetraploid. In hypertrophic cardiomyopathy (HCM), nucleic DNA are hyperploid compared to normal hearts. In HCM with obstruction, cell nuclei are tetraploid to octoploid. In HCM without obstruction, cell nuclei can be recognized as both tetraploid to octoploid and hexaploid to decaploid, having two kinetic patterns. In congestive cardiomyopathy DNA values are lower compared to control, and nucleic DNA has a tendency to hypodiploidy. Correlation between DNA values and wall thickness are highest. Correlation between DNA and other left ventricular functions (ejection fraction, mean VCF, and Vmax) is also high.

 

[ohyeahbaby]

I know for a fact that ***some*** hypertrophied "regular" heart muscle cells have extra DNA in them. I remember this because I was very surprised to hear our histology professor in year 1 say that. I just don't know by how much the DNA increases, the percentage of hypertrophied cells that are like that, and I have absolutely nothing to support this.

 

[chaotic mind]

It says in my notes that it happens because the cell arrests in the cell cycle without undergoing mitosis. But what makes it not undergo mitosis?

I just read that megakaryoblasts also become hyperploid(upto 64N) and they divide endomitotically.
So a cell increasing its ploidy and not undergoing mitosis not only seen in myocytes(cellular adaptation/pathologic conditions) but also in normal cells(like megakaryoblasts).

And as to your question why the myocyte doesn't divide - no idea