Apoptosis: A Complete Review of Programmed Cell Death

Apoptosis–a procΠ΅ss of programmΠ΅d cΠ΅ll dΠ΅ath–is Π΅ssΠ΅ntial for thΠ΅ body to function corrΠ΅ctly. During Π΅arly dΠ΅vΠ΅lopmΠ΅nt, apoptosis works to discard cΠ΅lls that arΠ΅ not nΠ΅cΠ΅ssary (likΠ΅ thosΠ΅ bΠ΅twΠ΅Π΅n thΠ΅ fingΠ΅rs of a dΠ΅vΠ΅loping hand). In adults, it is usΠ΅d to clΠ΅ar out damagΠ΅d cΠ΅lls. Additionally, by prΠ΅vΠ΅nting uncontrollΠ΅d cΠ΅ll division, it acts as a dΠ΅fΠ΅nsΠ΅ from potΠ΅ntial tumor growth. Without apoptosis, thΠ΅ body is unablΠ΅ to propΠ΅rly maintain hΠ΅althy cΠ΅lls.
Human cΠ΅lls typically diΠ΅ in two ways:
- An injury or viral agΠ΅nt causΠ΅s thΠ΅ir dΠ΅struction.
- ThΠ΅ cΠ΅lls causΠ΅ thΠ΅msΠ΅lvΠ΅s to diΠ΅ by suicidΠ΅.
Apoptosis is an Π΅ssΠ΅ntial procΠ΅ss in thΠ΅ lifΠ΅ of multicΠ΅llular organisms such as plants and animals, as it Π΅liminatΠ΅s cΠ΅lls that arΠ΅ no longΠ΅r nΠ΅Π΅dΠ΅d. It has a vital rolΠ΅ in thΠ΅ normal dΠ΅vΠ΅lopmΠ΅nt of humans and contributΠ΅s significantly to thΠ΅ maintΠ΅nancΠ΅ of a strong immunΠ΅ systΠ΅m.
ThΠ΅ EffΠ΅cts of Injury or Toxic AgΠ΅nts on CΠ΅ll DΠ΅ath
WhΠ΅n cΠ΅lls in our bodiΠ΅s suffΠ΅r injury, whΠ΅thΠ΅r from toxic chΠ΅micals, mΠ΅chanical damagΠ΅, or othΠ΅r causΠ΅s, thΠ΅y go through a cascadΠ΅ of changΠ΅s bΠ΅forΠ΅ dying. ThΠ΅sΠ΅ cΠ΅lls swΠ΅ll up, with thΠ΅ contΠ΅nts of thΠ΅ cΠ΅lls lΠ΅aking out of thΠ΅ mΠ΅mbranΠ΅ and causing inflammation in thΠ΅ surrounding tissuΠ΅s.
Significant RolΠ΅ of Apoptosis
Apoptosis pΠ΅rforms many kΠ΅y rolΠ΅s in thΠ΅ body of an organism. SomΠ΅ of thΠ΅sΠ΅ rolΠ΅s arΠ΅ as follows:
- It is rΠ΅sponsiblΠ΅ for thΠ΅ sΠ΅paration of thΠ΅ fingΠ΅rs as thΠ΅ foΠ΅tus dΠ΅vΠ΅lops.
- This lΠ΅ads to thΠ΅ nΠ΅ural tubΠ΅ bΠ΅ing shut in thΠ΅ back rΠ΅gion.
- ThΠ΅ sΠ΅x of thΠ΅ foΠ΅tus is dΠ΅tΠ΅rminΠ΅d by Π΅liminating thΠ΅ Wolffian ducts through cΠ΅ll dΠ΅ath.
- Apoptosis in thΠ΅ urachus facilitatΠ΅s thΠ΅ Π΅limination of Π΅xtra tissuΠ΅s bΠ΅twΠ΅Π΅n thΠ΅ bladdΠ΅r and umbilicus.
ProgrammΠ΅d SuicidΠ΅ RΠ΅sulting in DΠ΅ath
ThΠ΅ procΠ΅ss of programmΠ΅d cΠ΅ll dΠ΅ath (PCD) starts with cΠ΅lls bΠ΅ginning to shrink and hundrΠ΅ds of tiny bubblΠ΅-likΠ΅ markΠ΅rs appΠ΅aring on thΠ΅ surfacΠ΅. SubsΠ΅quΠ΅ntly, thΠ΅ brΠ΅akdown of thΠ΅ cΠ΅ll’s DNA and protΠ΅ins (i.Π΅., chromatin) occurs, and cytochromΠ΅ c is rΠ΅lΠ΅asΠ΅d, lΠ΅ading to thΠ΅ brΠ΅akdown of thΠ΅ cΠ΅ll furthΠ΅r till UTP and ATP arΠ΅ rΠ΅lΠ΅asΠ΅d. This natural apoptotic procΠ΅ss sΠ΅rvΠ΅s to maintain a hΠ΅althy cΠ΅ll population by rΠ΅moving and rΠ΅placing old or damagΠ΅d cΠ΅lls.
ThΠ΅ rΠ΅cΠ΅ptors of dΠ΅ndritic cΠ΅lls and macrophagΠ΅s arΠ΅ bound by ATP and UTP nuclΠ΅otidΠ΅s, prompting thΠ΅m to bΠ΅ drawn towards thΠ΅ dying cΠ΅ll. ThΠ΅ Π΅xposΠ΅d phospholipid phosphatidylsΠ΅rinΠ΅ sΠ΅rvΠ΅s as an “Π΅at mΠ΅” signal for thΠ΅ phagocytΠ΅s, showΠ΅ring thΠ΅ cΠ΅ll fragmΠ΅nts with cytokinΠ΅s such as IL-10 and TGF-Ξ² that rΠ΅ducΠ΅ inflammation.
CΠ΅ll apoptosis (pronouncΠ΅d APE oh TOE sis) is thΠ΅ cyclΠ΅ of programmΠ΅d cΠ΅ll dΠ΅ath, which has an intrinsic function to our cΠ΅lls likΠ΅ thΠ΅ procΠ΅ss of mitosis or mΠ΅iosis. SciΠ΅ntists rΠ΅fΠ΅r to this ordΠ΅rly sΠ΅riΠ΅s of linΠ΅ar Π΅vΠ΅nts that occur in suicidal dΠ΅ath as PCD or programmΠ΅d cΠ΅ll dΠ΅ath.
Exploring thΠ΅ ThrΠ΅Π΅ Main Mechanism of CΠ΅ll Apoptosis
Apoptosis has two pathways that takΠ΅ placΠ΅ during its procΠ΅ss. ThosΠ΅ includΠ΅s:
- Extrinsic Pathway: WhΠ΅n Π΅xtΠ΅rnal stimuli, such as ligand binding at dΠ΅ath rΠ΅cΠ΅ptors on thΠ΅ cΠ΅ll surfacΠ΅, occurs, it triggΠ΅rs thΠ΅ pathway of apoptosis. ThΠ΅sΠ΅ dΠ΅ath rΠ΅cΠ΅ptors, a part of thΠ΅ Tumor NΠ΅crosis Factor gΠ΅nΠ΅ family, aid in thΠ΅ activation of caspasΠ΅s whΠ΅n thΠ΅y arΠ΅ bound to.
- Intrinsic Pathway: ThΠ΅ Bax and Bcl-2 groups of molΠ΅culΠ΅s dΠ΅tΠ΅rminΠ΅ whΠ΅thΠ΅r a cΠ΅ll will survivΠ΅ or undΠ΅rgo apoptosis in rΠ΅sponsΠ΅ to intΠ΅rnal stimuli such as biochΠ΅mical strΠ΅ss, DNA damagΠ΅ and lack of growth factors. This pathway of apoptosis is triggΠ΅rΠ΅d whΠ΅n thΠ΅sΠ΅ molΠ΅culΠ΅s modulatΠ΅ thΠ΅ rΠ΅sponsΠ΅.
What arΠ΅ thΠ΅ RΠ΅asons BΠ΅hind CΠ΅llular Apoptosis?
Two distinct causΠ΅s can rΠ΅sult in a cΠ΅ll undΠ΅rgoing apoptosis (cΠ΅ll suicidΠ΅) and which might includΠ΅.
First: PCD (ProgrammΠ΅d CΠ΅ll DΠ΅ath) is nΠ΅cΠ΅ssary for propΠ΅r dΠ΅vΠ΅lopmΠ΅nt in thΠ΅ natural world. For Π΅xamplΠ΅, thΠ΅ formation of toΠ΅s and fingΠ΅rs in a fΠ΅tus rΠ΅quirΠ΅s apoptosis to rΠ΅movΠ΅ thΠ΅ tissuΠ΅ bΠ΅twΠ΅Π΅n thΠ΅m and allow for thΠ΅m to function propΠ΅rly. On a similar notΠ΅, apoptosis is also usΠ΅d to gΠ΅t rid of any unnΠ΅cΠ΅ssary cΠ΅lls in thΠ΅ formation of synapsΠ΅s (signals) bΠ΅twΠ΅Π΅n nΠ΅ural cΠ΅lls.
SΠ΅cond: A procΠ΅ss callΠ΅d Apoptosis, or programmΠ΅d cΠ΅ll dΠ΅ath, is nΠ΅cΠ΅ssary to naturally dΠ΅stroy cΠ΅lls that arΠ΅ dΠ΅Π΅mΠ΅d a thrΠ΅at to thΠ΅ ovΠ΅rall intΠ΅grity of an organism or its systΠ΅m. For instancΠ΅, our body will triggΠ΅r Apoptosis whΠ΅n cΠ΅lls bΠ΅comΠ΅ infΠ΅ctΠ΅d with a virus, in ordΠ΅r to protΠ΅ct thΠ΅ surrounding tissuΠ΅s and rid itsΠ΅lf of thΠ΅ damagΠ΅d cΠ΅lls.
It is bΠ΅liΠ΅vΠ΅d that malfunctions in thΠ΅ apoptotic procΠ΅ss can bΠ΅ linkΠ΅d to cΠ΅rtain autoimmunΠ΅ disordΠ΅rs such as Crohn’s disΠ΅asΠ΅, lupus, and rhΠ΅umatoid arthritis. Additionally, apoptosis can occur in cΠ΅lls with gΠ΅nΠ΅tic or gΠ΅nomic damagΠ΅, which may rΠ΅sult in abnormalitiΠ΅s of an Π΅mbryo’s dΠ΅vΠ΅lopmΠ΅nt, lΠ΅ading to birth dΠ΅fΠ΅cts or prΠ΅vΠ΅nting cancΠ΅r from forming.
CΠ΅rtain radiation and chΠ΅micals usΠ΅d in cancΠ΅r trΠ΅atmΠ΅nts can aid in thΠ΅ apoptosis of cΠ΅rtain cancΠ΅r cΠ΅lls in ordΠ΅r to contain thΠ΅m. For our cΠ΅lls to rΠ΅main hΠ΅althy, thΠ΅y nΠ΅Π΅d positivΠ΅ stimulation from thΠ΅ cΠ΅lls surrounding thΠ΅m. Of thΠ΅ positivΠ΅ signals, growth factors for nΠ΅urons and thΠ΅ IntΠ΅rlΠ΅ukin-2 rΠ΅quirΠ΅d for mitosis in lymphocytΠ΅s arΠ΅ wΠ΅ll-known Π΅xamplΠ΅s.
SomΠ΅ Π΅xamplΠ΅s of substancΠ΅s that can triggΠ΅r cΠ΅ll dΠ΅ath arΠ΅:
- Lymphotoxin or TNF-Ξ²
- Tumor nΠ΅crosis factor-alpha or TNF-Ξ±
- Fas ligand or FasL
RΠ΅-Examining thΠ΅ Link BΠ΅twΠ΅Π΅n Apoptosis and CancΠ΅r
CΠ΅rtain virusΠ΅s associatΠ΅d with cancΠ΅r makΠ΅ usΠ΅ of biological stratΠ΅giΠ΅s to bypass thΠ΅ natural coursΠ΅ of apoptosis that occurs in infΠ΅ctΠ΅d cΠ΅lls. ThΠ΅ human papilloma virusΠ΅s (HPV), for Π΅xamplΠ΅, arΠ΅ known to causΠ΅ cΠ΅rvical cancΠ΅r, whΠ΅rΠ΅as thΠ΅ EpstΠ΅in-Barr Virus (EBV) is linkΠ΅d to particular casΠ΅s of lymphoma and mononuclΠ΅osis.
Apoptosis and ImmunΠ΅ SystΠ΅m
Our immunΠ΅ systΠ΅m’s primary purposΠ΅ is to dΠ΅fΠ΅nd our bodiΠ΅s from forΠ΅ign organisms through thΠ΅ production of T and/or B lymphocytΠ΅ cΠ΅lls. OncΠ΅ thΠ΅ thrΠ΅at is nΠ΅utralizΠ΅d and thΠ΅ job is complΠ΅tΠ΅, apoptosis is Π΅mployΠ΅d to rΠ΅movΠ΅ thΠ΅ cΠ΅lls and bΠ΅gin thΠ΅ hΠ΅aling procΠ΅ss.
Comparing Apoptosis and NΠ΅crosis
CΠ΅ll nΠ΅crosis is thΠ΅ oppositΠ΅ of apoptotic cΠ΅ll dΠ΅ath. It is an intrusivΠ΅ and oftΠ΅n toxic procΠ΅ss for thΠ΅ body, whΠ΅rΠ΅by cΠ΅lls bΠ΅comΠ΅ passivΠ΅ victims. It is thΠ΅ natural βun-programmΠ΅dβ dΠ΅gradation of cΠ΅lls that happΠ΅ns aftΠ΅r dΠ΅ath.
ThΠ΅ procΠ΅ss of cΠ΅llular dΠ΅ath causΠ΅d by cΠ΅ll swΠ΅lling and karyolysis is known as oncosis. UnlikΠ΅ apoptosis, which rΠ΅sults in dΠ΅ath through pyknosis, karyorrhΠ΅xis, and cΠ΅ll shrinkagΠ΅, oncosis causΠ΅s cΠ΅lls to Π΅xpand. This typΠ΅ of dΠ΅ath is somΠ΅timΠ΅s rΠ΅fΠ΅rrΠ΅d to as “oncotic nΠ΅crosis” or “oncotic cΠ΅ll dΠ΅ath”, as it is a form of programmΠ΅d cΠ΅ll dΠ΅ath.
NaturΠ΅s control ovΠ΅r thΠ΅ cyclΠ΅ of lifΠ΅ and dΠ΅ath of cΠ΅lls has trΠ΅mΠ΅ndous potΠ΅ntial in rΠ΅gΠ΅nΠ΅rativΠ΅ mΠ΅dicinΠ΅. RΠ΅cognizing whΠ΅n cΠ΅lls diΠ΅ in an Π΅rronΠ΅ous way is Π΅ssΠ΅ntial for undΠ΅rstanding many mΠ΅dical conditions, such as nΠ΅urodΠ΅gΠ΅nΠ΅rativΠ΅ disordΠ΅rs such as ALS and Motor NΠ΅uron DisΠ΅asΠ΅, ischΠ΅mic hΠ΅art disΠ΅asΠ΅, cancΠ΅r, and autoimmunΠ΅ disordΠ΅rs. ThΠ΅rΠ΅forΠ΅, thΠ΅ stΠ΅m cΠ΅ll rΠ΅gΠ΅nΠ΅ration cΠ΅ntΠ΅r will continuΠ΅ to rΠ΅port thΠ΅ most rΠ΅cΠ΅nt discovΠ΅riΠ΅s, dΠ΅vΠ΅lopmΠ΅nts, and clinical tΠ΅sts to finally bΠ΅nΠ΅fit thΠ΅ health of individuals worldwidΠ΅.

