*4.2.3. Calcium iron*

The concentration of calcium in vivo is the key role in maintain the permeatability of mitochondrial membrane. The increased intra-mitochondrial calcium can result in enhanced ROS, Furthermore, cytochrome c will be stimulated to release. [46] And calcium also trigger

the ER stress, and then activate JNK pathway, afterwards, JNK activation can stimulate Bax activation; Moreover, calcuim can regulate the cysteine protease calpain, It's well known that calpain participate in the cell proliferation, cell cycle, and apoptosis. Calpain can cleave the N terminal of Bax and generate a proapoptotic fragment, and in the same time, the cells will enter the apoptosis. In a brief, calcium can trigger Bcl-2 independent cytochrome c release, and through regulating the activity of the calpain, calcium iron can play its roles in modulating the apoptosis. [47]. Beside involving in the apoptosis, Cacium iron can take part in many other signal pathways by controlling the iron channel's open or close.

Extrinsic and Intrinsic Apoptosis Signal Pathway Review 17

brain tissue damage. In the ischemia/reperfusion injury tissue, the intracellular calcium and ROS level will increased, these factors all contribute to induce AIF to release and translocate to the nucleus, in the end, the caspase-independent apoptosis will happen, if we prevent this cell death, the prognosis of ischemia/reperfusion will be favorable. However, if we promote this cell death in cancer cells , the cancer cells will form several apoptotic body containing the cell content, and did not release the cytosol and will not lead to the fatal inflammation, in this way, the patient will have the least bad effect and help them to fight against the disease; Apoptosis occur accompanying with inflammation, inflammasome in the cells may be related with the caspase family, the tissues or organs may be existed the apoptosis and deduct the immune reaction which induced by the inflammation, we proposed that if the apoptosis do not happen in this case, the persistent proliferation and serious inflammation

Apoptosis is the normal cell death in order to maintain the balance of homeostasis. Unlikely the necrosis can induce inflammation. apoptosis can give little side effects. So as the therapy targets, apoptosis will be the reasonable way to cure some diseases. such as obesity [50], cancer, neuron-degeneration diseases and so on. Due to the genetic changes often existed in the human tumor cells and apoptosis have the little side effect in curing some diseases, ,it is not surprised that the antitumor drug have direct or indirect to target the apoptosis pathway molecular. The identification of the apoptosis signal pathways, and together with the increased knowledge about the apoptosis mechanisms, have given the great lots of evidences for the discovery of new drugs which can target to the

Above all, from the life beginning and during the whole life, apoptosis always existed to make our life healthy. Apoptosis can not release the intracellular content in the end, this cell process will not lead to inflammation, and therefore, apoptosis is the injury-limiting mode of cell disposal. Above all, it is necessary and meaningful to research the apoptosis mechanism, it will give the deep inside to guild the clinical treatment and drug design. Beside, in the nutrition research area, there are some native compounds which can be from the fruits, vegetables and some marine products can help for healthy through inducing or inhibiting apoptosis signal pathway, so knowing the mechanism of apoptosis deeply not only good for guiding people to use proper drug or balance dietary in daily life, but also far

*College of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin, China* 

*Chinese Academy of Medical Science & Peking Union Medical School, China* 

will be occurred in cancer cells, this is bad for the organism.

reaching impacts in design some new drugs.

*Tianjin Key Laboratory of Food Biotechnology,* 

**5.1. Drug design** 

apoptosis.

**Author details** 

Zhao Hongmei
