NAMA : INDAH WULANDARI

NIM : 1500013043

KELAS : CD

MATA KULIAH : BIOPSIKOLOGI

JUDUL : Regulation of Circadian Rhythms in Mammals by Behavioral

Arousal

HALAMAN : 315 - 316

Signaling Pathways and Molecular Mechanisms

Signaling Pathways dan Mekanisme Molekuler

Although effects on immediate early genes are interesting, these genes are not gears of the
circadian clock.

Meskipun efek pada gen awal segera menarik, gen ini bukanlah gigi dari jam sirkadian

The SCN circadian clock is an ensemble of cell autonomous circadian “clock cells” that oscillate
as a result of autoregulatory transcription translation feedback loops involving so-called circadian clock
genes and their protein products (Antle & Silver, 2005).

Jam sirkadian SCN adalah ensemble sel jam sirkadian otonom sel yang berosilasi sebagai hasil
dari rangkaian umpan balik terjemahan transkripsi autoregulator yang melibatkan gen jam
sirkadian yang disebut dan produk protein mereka (Antle & Silver, 2005)

Antle, M. C., & Silver, R. (2005). Orchestrating time: Arrangements of the brain circadian clock.
Trends in Neuroscience, 28, 145–151. doi: 10.1016/j.tins.2005.01.003

Expression of the period and cryptochrome genes per1, per2, cry1, and cry2 are regulated by e-
box elements in their promoters. Transcription is initiated when CLOCK and BMAL1 bind to the e-
boxes.

Ekspresi periode dan gen cryptochrome per1, per2, cry1, dan cry2 diatur oleh elemen e-box pada
promotor mereka. Transkripsi dimulai saat CLOCK dan BMAL1 mengikat ke e-box.

mRNA accumulates over the course of the day and is translated into the corresponding proteins
with about a 6-hr lag.

mRNA terakumulasi sepanjang hari dan diterjemahkan ke dalam protein yang sesuai dengan
sekitar jeda 6 jam
 The proteins dimerize and translocate back into the nucleus in the early night where they inhibit
the activity of CLOCK and BMAL1, thereby turning off their own expression. As PER and CRY protein
levels fall over the night, inhibition of transcription ceases, and transcription can be reinitiated.

Protein dimerisasi dan ditranslokasi kembali ke nukleus di malam hari di mana mereka
menghambat aktivitas JAM dan BMAL1, sehingga mematikan ekspresi mereka sendiri. Seiring tingkat
protein PER dan CRY turun sepanjang malam, penghambatan transkripsi berhenti, dan transkripsi dapat
dimulai kembali.

There are supporting side loops that regulate the expression of BMAL1, and other proteins that
regulate the stability of PER, such as casein kinase 1(Mohawk & Takahashi, 2011).

Ada sisi pendukung loop yang mengatur ekspresi BMAL1, dan protein lain yang mengatur
stabilitas PER, seperti casein kinase 1 (Mohawk & Takahashi, 2011).

Phase shifts of circadian rhythms must ultimately culminate in an adjustment of these

transcription-translation feedback loops

Pergeseran fase ritme sirkadian pada akhirnya harus berujung pada penyesuaian loop umpan balik
terjemahan transkripsi ini.

Mohawk, J. A., & Takahashi, J. S. (2011). Cell autonomy and synchrony of suprachiasmatic
nucleus circadian oscillators. Trends in Neuroscience, 34, 349–358. doi:
10.1016/j.tins.2011.05.003

Nonphotic manipulations appear to adjust the phase of the circadian clock by causing a
decrease in the expression of the per genes in the SCN.

Manipulasi nonfotik tampaknya menyesuaikan fase jam sirkadian dengan menyebabkan

penurunan ekspresi gen per SCN

Levels of the mRNA for both per1 and per2 are rapidly down regulated following
daytime wheel confinement (Maywood & Mrosovsky, 2001; Maywood et al., 1999).

Tingkat mRNA untuk kedua per1 dan per2 cepat turun diatur setelah pengekangan roda
siang hari (Maywood & Mrosovsky, 2001; Maywood et al., 1999).

Maywood, E. S., Mrosovsky, N., Field, M. D., & Hastings, M. H. (1999). Rapid down-regulation
of mammalian period genes during behavioral resetting of the circadian clock.
Proceedings of the National Academy of Sciences of the United States of America, 96,
15211–15216. doi:10.1073/pnas.96.26.15211

This rapid decrease in mRNA should eventually lead to a premature rise in expression on
subsequent cycles, yielding the expected phase advance. The same decrease in per1 occurs
following sleep deprivation (see Figure 5).
 Penurunan mRNA yang cepat ini pada akhirnya akan menyebabkan kenaikan ekspresi
prematur pada siklus berikutnya, menghasilkan kemajuan fase yang diharapkan. Penurunan yang
sama pada per1 terjadi setelah kurang tidur (lihat Gambar 5).

In fact, directly knocking down per1 levels with antisense oligonucleotides during the
day induces nonphotic phase shifts (Hamada,Antle, & Silver, 2004)
Sebenarnya, secara langsung menurunkan level per1 dengan oligonukleotida antisense
pada siang hari menginduksi pergeseran fasa nonfotik (Hamada, Antle, & Silver, 2004)

Hamada, T., Antle, M. C., & Silver, R. (2004). The role of period1 in non-photic resetting of the
hamster circadian pacemaker in the suprachiasmatic nucleus. Neuroscience Letters, 362,
87–90. doi: 10.1016/. neulet.2004.02.061

The mechanism by which nonphotic signals from NPY, serotonin, acetylcholine, and
other neurochemicals lead to altered gene expression is still being determined.

Mekanisme dimana sinyal nonphotic dari NPY, serotonin, asetilkolin, dan neurokimia
lainnya menyebabkan ekspresi gen yang berubah masih ditentukan.

These neurotransmitters all act through G protein coupled receptors, and therefore
alterations in second messenger signaling cascades likely leads to the changes in per gene
expression.

Neurotransmiter ini bertindak melalui reseptor protein G yang digabungkan, dan oleh
karena itu, perubahan pada kaset sinyal messenger kedua kemungkinan mengarah pada
perubahan pada ekspresi gen.