Autophagy and Apoptosis
The p53, a protein that assists in the cell cycle arrest, takes the cell out of the cycle for autophagy and repairs, or self-destruction by apoptosis. The eventual viable cell then re-enters the cycle. The p53 gene is a potent anti-oncogene. When mutated, the cell will continue to carry out cell-cycling, unabated, and replication will continue--including of the telomere repeats-- as normal. There are isoforms of p53 involved, which sense the need for either apoptosis, or autophagy and repairs.
Autophagy is anti-inflammatory as the cell is kept viable, shows no signs of distress(damage), safe, perhaps, for some cell shrinking(due to self-cannibalization of up to 50%)-- thus, there is no need to call for inflammatory cells. Equally, autophagy disposes of the inflammasome. Conversely, inflammation prevents autophagy, hence the need to reduce inflammation to promote the more useful and desirable phagocytosis, since autophagy disposes of intracellular pathogens and debris.
Some intracellular organisms, however, may prevent apoptosis in the host cell by promoting autophagy through the suppression of metabolism via, perhaps, some hormonal stabilization of the membrane. It should be recalled that autophagy is prompted in response to either metabolic nutrients and energy deficiency, or exhaustion.
There are, however, pathogens(active infections with cytosolic or nuclear biofilms, including TB, having porin) and toxins, such as amyloid, that punch holes in the autophagosomes and abort autophagy and phagocytosis. These entities also affect the endoplasmic reticulum and mitochondria--organelles, equally surrounded by the lipid bilayer. Such event will lead to oxidative and endoplasmic stresses, resulting in protein denaturation, misfolding and apoptosis. Calcium and zinc are required for autophagy, though excess of the former may modulate too much activation, of its own making, and eventually cause cell death by apoptosis--through the production of free radicals. The cell shrivels, from calcium-dependent Chloride channel activation and cellular fluid loss. Thus, eventual tissue atrophy may precede an initial hypertrophy. Hence, kidney proliferation precedes self-destruct, and type2 diabetes revolves around increased insulin secretion--then tolerance(insulin resistance)--and finally the lack of it. There are various genes involved in this activation-deactivation interplay.
Dr. Oliver Verbe Birnso, MD.
Autophagy is anti-inflammatory as the cell is kept viable, shows no signs of distress(damage), safe, perhaps, for some cell shrinking(due to self-cannibalization of up to 50%)-- thus, there is no need to call for inflammatory cells. Equally, autophagy disposes of the inflammasome. Conversely, inflammation prevents autophagy, hence the need to reduce inflammation to promote the more useful and desirable phagocytosis, since autophagy disposes of intracellular pathogens and debris.
Some intracellular organisms, however, may prevent apoptosis in the host cell by promoting autophagy through the suppression of metabolism via, perhaps, some hormonal stabilization of the membrane. It should be recalled that autophagy is prompted in response to either metabolic nutrients and energy deficiency, or exhaustion.
There are, however, pathogens(active infections with cytosolic or nuclear biofilms, including TB, having porin) and toxins, such as amyloid, that punch holes in the autophagosomes and abort autophagy and phagocytosis. These entities also affect the endoplasmic reticulum and mitochondria--organelles, equally surrounded by the lipid bilayer. Such event will lead to oxidative and endoplasmic stresses, resulting in protein denaturation, misfolding and apoptosis. Calcium and zinc are required for autophagy, though excess of the former may modulate too much activation, of its own making, and eventually cause cell death by apoptosis--through the production of free radicals. The cell shrivels, from calcium-dependent Chloride channel activation and cellular fluid loss. Thus, eventual tissue atrophy may precede an initial hypertrophy. Hence, kidney proliferation precedes self-destruct, and type2 diabetes revolves around increased insulin secretion--then tolerance(insulin resistance)--and finally the lack of it. There are various genes involved in this activation-deactivation interplay.
Dr. Oliver Verbe Birnso, MD.
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