Notes

AUTOPHAGIC CELL DEATH
The first description of lysosomes, and indeed the name, included the
assumption that the rupture of lysosomes was the common form of cell
death. lizozomun ilk tanımı ve asıl itibariyle adı; lizozomun parçalanması (ayrışması) hücre ölümünün genel Kabul görmüş bir biçimidir varsayımını içerir. This conclusion was apparently valid for the specific situation of
carbon tetrachloride toxicity in liver, in which the CCl4 could dissolve lysosomal and cell membranes, but it proved to be a simplistic interpretation of
most other cell deaths. Bu çıkarım, karaciğerdeki carbon tetrachloride zehirlenmesi ile ilgili özel bir durum için geçerli gibi görünse de, ki; cc14 lizozomlarla bağlantılı durumlar ve hücre zarında çözünmeye (bölünme) neden olur; diğer hücre ölümlerinin basit bir yorumundan başa birşey olmadığı kanıtlanmıştır. (Nevertheless, the discovery launched a wide-rangingevaluation of lysosomal activity in cell death, an active field through the1970s. These studies led to the conclusion that, in developmental cell deaths,
the pool of lysosomal enzymes may be expanded as cell death is activated
(Lockshin, 1969a; Lockshin and Williams, 1965d) or merely “activated” (formation of autophagic vacuoles rather than primary lysosomes—Helminen
and Ericsson, 1970). ( mamafih, 1970 lere kadar aktif bir calisma sahasi olarak, hucre olumlerindeki lizozomal aktivite ile ilgili genis capta degerlendirmeler ortaya cikmistir. Gelisimsel hucre olumlerindeki bu calismalar bizi, Hucre olumleri active edildiginde ya da tamamiyle active edildiginde lizozomal enzim havuzunun genisleyebilecegi sonucuna goturur.

As interpreted today, the lysosomes detected are either
the lysosomes of phagocytic cells, or there is an expansion of the lysosomal
system driven primarily by the formation of autophagic vacuoles. Bugun yorumlandigi sekliyle, lizozomlar ya phagocytic hucrelerdir, ya da esas itibariyle autophagic hucre bosluklarinin bir formunun neden oldugu lizozomal systemde bir genisleme soz konusudur.

As is explained in the chapter by Bursch et al., autophagic vacuoles are most
clearly seen in large, postmitotic, sedentary cells. Bursch bolumunde aciklandigi uzere, autophagic hucre bosluklari, en cok buyuk, mitoz sonrasi ve yerlesik hucrelerde gorulurler.

In these cells, the primary consideration is the removal of large amounts of cytoplasm, and the destruction of DNA is not a high priority. Bu hucrelerde ozellikle goz onunde bulundurmamiz gereken, buyuk miktarda sitoplazma ayrisimidir. Dna yikimi yuksek oncelige sahip degildir.

Thus, the early activities are the lysosomal destruction of cytoplasm, with DNA degradation occurring very late or not at all, and generally these deaths are not caspase-driven (see nextsection). Dolayisiyla, stoplazmadaki lizozomal yikimin ilk faaliyetleri dna bozulmasiyla birlikte ya cok gec olur ya da hic olmaz ve genellikle bu olumler caspase nedenlidir. (caspase= bir tur enzim) Much remains to be learned of autophagic cell death. For instance, autophagy is often seen in atrophying cells, in which cytoplasm is reduced
and the cell may enter a quiescent state, but the nucleus and the cell survive. Ornegin, atrofaji, genellikle atrofajik hucrelerde gorulur, stoplazmanin azaldigi ve belki de hucrenin dinlenme durumuna gectigi fakat cekirdek ve hucrenin hayatta kaldigi.

The turning point or threshold is not well understood, although it may
follow a schematic as presented by Tolkovsky, Bampton, and Goemans. konu ile ilgili Donum noktasi ya da anlasilma esigi seviyesi kolay olmayabilir, yine de
Tolkovsky, Bampton, ve Goemans ‘in konu ile ilgili sematik anlatimina goz gezdirilebilir.

Also, we know very little about the mechanisms by which the membranes
of the autophagic vacuoles are formed, how they encircle target organelles
or regions of cytoplasm, or how target organelles, such as mitochondria,
expose markers or signals that identify them as targets. Many of the components are being identified (Klionsky and Emr, 2000), but the transients and
control mechanisms remain to be explored. Tum bu gelismelere ragmen, atofik hucre bosluklarindaki ceperin nasil olustugu, hedef organelleri ve stoplazmayi nasil cevreledikleri veya mitokondri gibi hedef organelleri nasil hedef olarak belirledikleri ya da hedef olmak uzere saptadiklari gibi mekanizmalarin nasil isledikleri konusunda bilgimiz sinirlidir. Aslinda bircok konu (Klionsky and Emr, 2000) anlasilabilir, fakat transitler ve control mekanizmalari hala kesfedilmeyi ve arastirilmayi beklemektedir.


NECROSIS
For a metazoan it is always preferable to control the death of cells, to contain
the escape of potentially destructive molecules such as proteases and inflammatory cytokinins as well as invasive organisms such as viruses. Bir metazoan icin her zaman hucre olumlerini control etmek her zaman tercih edilebilir bir durumdur protozoa, enflamatuvar etkiye sahip sitokin ve virusler gibi istilaci organizmalar gibi yikici olma potansiyeline sahip molekullerin kacmalarini engellemek .

Apoptosis, described below, contains the dying cell and avoids inflammation. Viruses,
on the other hand, typically attempt to avoid this effective virus-controlling
route.
Apoptoz, asagida tarif edildigi sekliyle hucre olumlerini dikkate alir, enflamasyon kapsam disidir. Diger taraftan, virusler bu virus control edici donguden kacinmaya calisirlar.

Their goal is not to lose their host cell or, if this is not an option, to
provoke lysis and an inflammatory response through which they can escape.
amaclari, konak hucreleri kaybetmemektir, eger boyle bir secenek yok ise, Lizozleri provoke ederler ve kacabilecekleri enflamasyona neden olucu bir cevap bulmaya calisirlar.

Therefore, viruses often have apoptosis-blocking mechanisms. Iste bu nedenle, virusler s apoptozlari bloke edici bir mekanizmaya sahiptirler.
If the cell is very sick and cannot undergo apoptosis, it follows the route
of necrosis. Eger hucre cok hasta ve apoptoza maruz kalamiyorsa nekroz yolunu izler.

Likewise, when a cell is suddenly confronted with a severe stress,
such as a sharp change in tonicity, ion concentration, or pH, of the extracellular medium; or if all energy resources are suddenly extinguished, as in an
infarct; if an increase or decrease of temperature makes the maintenance of
homeostasis impossible; or if the integrity of the cell or organelle membranes
is compromised by a solvent or physical disrupter of a membrane, the cell
will simply rupture. Ayni sekilde, bir hucre aniden siddetli stresse maruz kalirsa,, ornegin iyon konsantrasyonu, ph veya tonasitesinde ciddi degisim; enfarktuste oldugu gibi
aniden tum enerji kaynaklari tukenirse, isisinda homeostasis imkansiz kilan herhangibir artma veya azalma olursa ya da; hucrenin butunlugu ya da organel ceperler, fiziksel ya da herhangibir cozucu tarafindan bozulma riskine maruz kalirsa, hucre en basit anlamiyla parcalanacaktir.

The typical sequence is that mitochondrial failure will
allow entrance of Ca++ into mitochondria, swelling and rupture of mitochondria, loss of ion pumps, followed by loss of osmotic control of the cell,
osmotic swelling and lysis of the cell, invasion of macrophages and inflammation, and removal of the debris. In electron microscope images, nucleoplasm and cytoplasm show disorganized precipitation of proteins, and there
is no evidence of any active response of the cell to any stage of this disintegration
(Fig. 5). The process is not stepwise and may follow different sequences. Tipik siralanmada, mitokondriyal yetersizlik ca++ nin mitokondri icerisine alinmasi, mitokondrinin sismesi ve parcalanmasi, iyon pompalamasinin kaybi ve ardindan hucredeki osmotic kontrolun yok olmasi, hucrenin yikimi ve osmotic sisme, mikrofaj ve enflamasyonun o bolgeyi kusatmasi ve yikimin yok edilmesidir. Electron mikroskobunda nukleoplazma ve stoplazmada disorganize bir sekilde protein cokelmesi gorulur bu bozulmanin her hangibir asamasinda hucrenin aktif yaniti ile ilgili herhangibir kanit bulunmamaktadir. Bu proses derece derece (kademe kademe) degildir ve herhangibir farkli dizilim olusabilir.

AUTOPHAGIC CELL DEATH
The first description of lysosomes, and indeed the name, included the
assumption that the rupture of lysosomes was the common form of cell
death. lizozomun ilk tanımı ve asıl itibariyle adı; lizozomun parçalanması (ayrışması) hücre ölümünün genel Kabul görmüş bir biçimidir varsayımını içerir. This conclusion was apparently valid for the specific situation of
carbon tetrachloride toxicity in liver, in which the CCl4 could dissolve lysosomal and cell membranes, but it proved to be a simplistic interpretation of
most other cell deaths. Bu çıkarım, karaciğerdeki carbon tetrachloride zehirlenmesi ile ilgili özel bir durum için geçerli gibi görünse de, ki; cc14 lizozomlarla bağlantılı durumlar ve hücre zarında çözünmeye (bölünme) neden olur; diğer hücre ölümlerinin basit bir yorumundan başa birşey olmadığı kanıtlanmıştır. (Nevertheless, the discovery launched a wide-rangingevaluation of lysosomal activity in cell death, an active field through the1970s. These studies led to the conclusion that, in developmental cell deaths,
the pool of lysosomal enzymes may be expanded as cell death is activated
(Lockshin, 1969a; Lockshin and Williams, 1965d) or merely “activated” (formation of autophagic vacuoles rather than primary lysosomes—Helminen
and Ericsson, 1970). ( mamafih, 1970 lere kadar aktif bir calisma sahasi olarak, hucre olumlerindeki lizozomal aktivite ile ilgili genis capta degerlendirmeler ortaya cikmistir. Gelisimsel hucre olumlerindeki bu calismalar bizi, Hucre olumleri active edildiginde ya da tamamiyle active edildiginde lizozomal enzim havuzunun genisleyebilecegi sonucuna goturur.

As interpreted today, the lysosomes detected are either
the lysosomes of phagocytic cells, or there is an expansion of the lysosomal
system driven primarily by the formation of autophagic vacuoles. Bugun yorumlandigi sekliyle, lizozomlar ya phagocytic hucrelerdir, ya da esas itibariyle autophagic hucre bosluklarinin bir formunun neden oldugu lizozomal systemde bir genisleme soz konusudur.

As is explained in the chapter by Bursch et al., autophagic vacuoles are most
clearly seen in large, postmitotic, sedentary cells. Bursch bolumunde aciklandigi uzere, autophagic hucre bosluklari, en cok buyuk, mitoz sonrasi ve yerlesik hucrelerde gorulurler.

In these cells, the primary consideration is the removal of large amounts of cytoplasm, and the destruction of DNA is not a high priority. Bu hucrelerde ozellikle goz onunde bulundurmamiz gereken, buyuk miktarda sitoplazma ayrisimidir. Dna yikimi yuksek oncelige sahip degildir.

Thus, the early activities are the lysosomal destruction of cytoplasm, with DNA degradation occurring very late or not at all, and generally these deaths are not caspase-driven (see nextsection). Dolayisiyla, stoplazmadaki lizozomal yikimin ilk faaliyetleri dna bozulmasiyla birlikte ya cok gec olur ya da hic olmaz ve genellikle bu olumler caspase nedenlidir. (caspase= bir tur enzim) Much remains to be learned of autophagic cell death. For instance, autophagy is often seen in atrophying cells, in which cytoplasm is reduced
and the cell may enter a quiescent state, but the nucleus and the cell survive. Ornegin, atrofaji, genellikle atrofajik hucrelerde gorulur, stoplazmanin azaldigi ve belki de hucrenin dinlenme durumuna gectigi fakat cekirdek ve hucrenin hayatta kaldigi.

The turning point or threshold is not well understood, although it may
follow a schematic as presented by Tolkovsky, Bampton, and Goemans. konu ile ilgili Donum noktasi ya da anlasilma esigi seviyesi kolay olmayabilir, yine de
Tolkovsky, Bampton, ve Goemans ‘in konu ile ilgili sematik anlatimina goz gezdirilebilir.

Also, we know very little about the mechanisms by which the membranes
of the autophagic vacuoles are formed, how they encircle target organelles
or regions of cytoplasm, or how target organelles, such as mitochondria,
expose markers or signals that identify them as targets. Many of the components are being identified (Klionsky and Emr, 2000), but the transients and
control mechanisms remain to be explored. Tum bu gelismelere ragmen, atofik hucre bosluklarindaki ceperin nasil olustugu, hedef organelleri ve stoplazmayi nasil cevreledikleri veya mitokondri gibi hedef organelleri nasil hedef olarak belirledikleri ya da hedef olmak uzere saptadiklari gibi mekanizmalarin nasil isledikleri konusunda bilgimiz sinirlidir. Aslinda bircok konu (Klionsky and Emr, 2000) anlasilabilir, fakat transitler ve control mekanizmalari hala kesfedilmeyi ve arastirilmayi beklemektedir.


NECROSIS
For a metazoan it is always preferable to control the death of cells, to contain
the escape of potentially destructive molecules such as proteases and inflammatory cytokinins as well as invasive organisms such as viruses. Bir metazoan icin her zaman hucre olumlerini control etmek her zaman tercih edilebilir bir durumdur protozoa, enflamatuvar etkiye sahip sitokin ve virusler gibi istilaci organizmalar gibi yikici olma potansiyeline sahip molekullerin kacmalarini engellemek .

Apoptosis, described below, contains the dying cell and avoids inflammation. Viruses,
on the other hand, typically attempt to avoid this effective virus-controlling
route.
Apoptoz, asagida tarif edildigi sekliyle hucre olumlerini dikkate alir, enflamasyon kapsam disidir. Diger taraftan, virusler bu virus control edici donguden kacinmaya calisirlar.

Their goal is not to lose their host cell or, if this is not an option, to
provoke lysis and an inflammatory response through which they can escape.
amaclari, konak hucreleri kaybetmemektir, eger boyle bir secenek yok ise, Lizozleri provoke ederler ve kacabilecekleri enflamasyona neden olucu bir cevap bulmaya calisirlar.

Therefore, viruses often have apoptosis-blocking mechanisms. Iste bu nedenle, virusler s apoptozlari bloke edici bir mekanizmaya sahiptirler.
If the cell is very sick and cannot undergo apoptosis, it follows the route
of necrosis. Eger hucre cok hasta ve apoptoza maruz kalamiyorsa nekroz yolunu izler.

Likewise, when a cell is suddenly confronted with a severe stress,
such as a sharp change in tonicity, ion concentration, or pH, of the extracellular medium; or if all energy resources are suddenly extinguished, as in an
infarct; if an increase or decrease of temperature makes the maintenance of
homeostasis impossible; or if the integrity of the cell or organelle membranes
is compromised by a solvent or physical disrupter of a membrane, the cell
will simply rupture. Ayni sekilde, bir hucre aniden siddetli stresse maruz kalirsa,, ornegin iyon konsantrasyonu, ph veya tonasitesinde ciddi degisim; enfarktuste oldugu gibi
aniden tum enerji kaynaklari tukenirse, isisinda homeostasis imkansiz kilan herhangibir artma veya azalma olursa ya da; hucrenin butunlugu ya da organel ceperler, fiziksel ya da herhangibir cozucu tarafindan bozulma riskine maruz kalirsa, hucre en basit anlamiyla parcalanacaktir.

The typical sequence is that mitochondrial failure will
allow entrance of Ca++ into mitochondria, swelling and rupture of mitochondria, loss of ion pumps, followed by loss of osmotic control of the cell,
osmotic swelling and lysis of the cell, invasion of macrophages and inflammation, and removal of the debris. In electron microscope images, nucleoplasm and cytoplasm show disorganized precipitation of proteins, and there
is no evidence of any active response of the cell to any stage of this disintegration
(Fig. 5). The process is not stepwise and may follow different sequences. Tipik siralanmada, mitokondriyal yetersizlik ca++ nin mitokondri icerisine alinmasi, mitokondrinin sismesi ve parcalanmasi, iyon pompalamasinin kaybi ve ardindan hucredeki osmotic kontrolun yok olmasi, hucrenin yikimi ve osmotic sisme, mikrofaj ve enflamasyonun o bolgeyi kusatmasi ve yikimin yok edilmesidir. Electron mikroskobunda nukleoplazma ve stoplazmada disorganize bir sekilde protein cokelmesi gorulur bu bozulmanin her hangibir asamasinda hucrenin aktif yaniti ile ilgili herhangibir kanit bulunmamaktadir. Bu proses derece derece (kademe kademe) degildir ve herhangibir farkli dizilim olusabilir.