How does influx of calcium cause cell injury?
This elevated intracellular calcium concentration is responsible for cytoskeletal modifications which alter cell shape, the activation of phospholipases which results in perpetuation of membrane damage and finally, mitochondrial calcification.
What is the effect of increased intracellular calcium that leads to cell death?
There are also data suggesting that very high intracellular Ca2+ levels can promote cell death through necrosis, whereas lower intracellular Ca2+ increases induced by milder insults promote cell death through apoptosis (Choi, 1995; Nicotera and Orrenius, 1998).
Which mitochondrial enzymes are activated by influx of calcium ions in an apoptotic cell?
In the signaling routes of apoptosis, also the Ca2+-dependent phosphatases appear to play an important role. In particular, various apoptotic routes share the activation of the Ca2+-dependent serine–threonine phosphatase calcineurin through a process blocked by Bcl-2 (Shibasaki and McKeon, 1995).
What causes calcium influx and loss of calcium homeostasis?
Intracellular calcium and loss of calcium homeostasis. Increased ICF Ca+2 results from failure of energy dependent Ca+2-Mg+2 ATPase pump and is also related to increased membrane permeability. This event is considered the initial step of irreversible injury.
Is calcium toxic to cells?
There is considerable evidence that a number of toxic environmental chemicals target these Ca(2+) signaling processes, alter them, and induce cell death by apoptosis. In the second pathway, Ca(2+) has a direct toxic effect and its primary targets include the mitochondria and the endoplasmic reticulum (ER).
How does calcium cause apoptosis?
Rising Ca(2+) concentration in the cytoplasm causes Ca(2+) influx into mitochondria and nuclei. In mitochondria Ca(2+) accelerates and disrupts normal metabolism leading to cell death. In nuclei Ca(2+) modulates gene transcription and nucleases that control cell apoptosis.
How does calcium induce apoptosis?
Release of this stored Ca2+ and subsequent uptake by the mitochondria is a mechanism that can trigger apoptosis. Ca2+ accumulation in the mitochondria leads to mitochondrial membrane permeabilization by stimulating the opening of the mitochondrial permeability transition pore (mPTP, Orrenius et al., 2003).
How does calcium maintain homeostasis?
Calcium homeostasis regulates calcium flow to and from the bones. Calcitriol regulates the levels of calcium and phosphorus in the blood and helps maintain a healthy skeletal system. Bone resorption by osteoclasts releases calcium into the bloodstream, which helps regulate calcium homeostasis.
What causes calcium influx?
Oxidative stress causes Ca(2+) influx into the cytoplasm from the extracellular environment and from the endoplasmic reticulum or sarcoplasmic reticulum (ER/SR) through the cell membrane and the ER/SR channels, respectively. Rising Ca(2+) concentration in the cytoplasm causes Ca(2+) influx into mitochondria and nuclei.
Is calcium ion toxic?
Cellular and Molecular Toxicology While it has become clear that Ca2+ stimulates many cellular processes, such as muscle contraction, cellular proliferation, gene expression, secretion of hormones and neurotransmitters, exocytosis, and chemotaxis, it has also been realized that Ca2+ is very toxic.