Xue et al., J Plant Physiol Pathol 2017, 5:1
DOI: 10.4172/2329-955X.1000158
Review Article
Reactive Oxygen Species Act as
a Signal to Negatively Regulate
Cell Proliferation in Leaf
Development
Jingshi Xue1,2, Zhongnan Yang2 and Hai Huang1*
Abstract
It was generally thought that reactive oxygen species (ROS) are
toxic byproducts, because living organisms have acquired various
antioxidants and ROS-scavenging/detoxifying enzymes during
evolution to prevent excess ROS accumulation. In recent years,
there has been increasing evidence that ROS also have signaling
functions, and play important roles in controlling the development
of plants and animals by modifying certain key regulatory factors. In
these ROS-regulated processes, endogenous antioxidant systems
control ROS at an appropriate level, at which they are able to alter
the functions of their targets. In this review, we summarize the role
of an endogenous plant antioxidant, ferulic acid. We also discuss
questions, arising from the results obtained to date, regarding the
control of ROS and the possible existence of important factors
targeted by ROS in the regulation of cell proliferation.
Keywords
Cell proliferation; Ferulic acid; Leaf development; Reactive oxygen
species
Journal of Plant
Physiology & Pathology
a SciTechnol journal
capacity of plants, which changes upon illumination [6]. Alternative
oxidase was thought to influence ROS generation and to be involved in
cell survival in oxidative conditions [7,8]. Another equally important
factor is that, compared with animals, plants may have more efficient
and/or abundant antioxidants to buffer changing levels of ROS.
In our previous studies, we found that normal leaf growth and
development require the antioxidant, ferulic acid (FeA) [9]. It has
long been known that FeA plays multiple roles in the plant kingdom.
Firstly, it is an important precursor in lignin biosynthesis [10,11].
Secondly, it can be esterified to cell wall polysaccharides, forming
ferulate dimers that cross-link hemicelluloses to lignin, a process
that depletes H2O2 [12]. Thirdly, as a phenolic acid, FeA itself has an
antioxidant function, as verified in animal systems [13-15].
Ferulic acid, which is one of the most abundant phenolic acids
in plants, is biosynthesized through the general phenylpropanoid
pathway [16]. Cinnamoyl-CoA reductase 1 (CCR1) catalyzes the
conversion of feruloyl-CoA or/and other cinnamoyl-CoA esters into
coniferaldehyde, which is further reduced into cinnamyl alcohol by
cinnamyl alcohol dehydrogenase (CAD) enzymes before forming
lignin [11]. Mutations in the CCR1 gene were shown to strongly
increase FeA accumulation in Arabidopsis [9,17,18]. Because of its antioxidant function and its abundance, FeA is an important contributor
to control ROS levels in plants. This has been demonstrated by two
lines of evidence: first, ccr1 mutant plants accumulating high FeA
levels showed decreased ROS content; and second, the ccoaomt comt
loss-of-function double mutant, which lacked the FeA biosynthetic
enzymes caffeoyl CoA-O methyltransferase (CCOAOMT) and caffeic
acid O-methyltransferase (COMT), showed dramatically reduced
FeA levels leading to increased ROS content [9].
Living organisms generate reactive oxygen species (ROS) in
several different ways. Under normal circumstances, electron leakage
from electron transport chains followed by particular biochemical
steps is probably the major pathway of ROS production [1,2]. In
animals, both the mitochondria and endoplasmic reticulum leak a
considerable amount of superoxide radicals generated from molecular
oxygen, and this is likely to be the main source of ROS in cells [3]. In
plants, the mitochondria and endoplasmic reticulum also produce
superoxide radicals, but chloroplasts, the photosynthetic organelles
in plant cells, produce even greater amounts of ROS, not only as a
result of photosynthetic processes but also photorespiration processes
involving peroxisomes and mitochondria [4]. It was estimated that in
C3 plants at moderate- to high-light intensities, hydrogen peroxide
(H2O2, a type of ROS) production by the peroxisomes and chloroplasts
in a leaf may be up to 30–100 times faster than H2O2 production by
the mitochondria. Interestingly, plants appear to be more tolerant to
H2O2 than animals [5], probably because of the alternative oxidase
Phenotypic analyses have shown that either overly elevated or
reduced FeA levels severely affect leaf cell proliferation and plant
development. ccr1 mutants showed a reduced plant stature and
increased cell number in several tissues [9,17]. Strikingly, the ccoaomt
comt mutant showed an even smaller plant size with dramatically
reduced cell numbers and lethality at the seedling stage [19].
Addition of FeA to the medium partially rescued ccoaomt comt
plants, confirming the lack of FeA was the main cause of seedling
lethality in the ccoaomt comt mutant (Figure 1) [9]. Because 1) the
antioxidant N-acetyl-L-cysteine also partially rescued the ccoaomt
comt phenotypes, and, 2) the cad-c cad-d double mutant showed
a reduced lignin content (similar to that of ccr1) but had a normal
plant stature, it is possible that the defect in the anti-oxidant
function of FeA, rather than the defect in lignin biosynthesis,
is the reason for the visible changes in the phenotypes of these
mutants [9].
*Corresponding author: Hai Huang, National Laboratory of Plant Molecular
Genetics, Shanghai Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 300 Fenglin Road,
Shanghai 200032, China, Tel: +86-21-54924088; Fax: +86-21-54924015; E-mail:
[email protected]
The acquisition of the FeA-antioxidant system in plants during
evolution has special significance. Unlike cells in different organisms,
plant cells that contain chloroplasts for photoassimilation generate
extremely large amounts of ROS [5]. These ROS may affect various
biological processes leading to plant death if they are not removed
properly, as shown in the ccoaomt comt double mutant [9,20].
Because of its abundance, FeA may represent an antioxidant reservoir
to quench ROS in plant cells. Moreover, unlike other antioxidant
Received: September 9, 2016 Accepted: October 03, 2016 Published: October
08, 2016
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Citation: Xue J, Yang Z, Huang H (2017) Reactive Oxygen Species Act as a Signal to Negatively Regulate Cell Proliferation in Leaf Development. J Plant
Physiol Pathol 5:1.
doi: 10.4172/2329-955X.1000158
Figure 1: Phenotypes of ccoaomt comt double mutant are caused by the defective FeA level. Twelve-day-old wild-type (A) or ccoaomt comt (B, C)
seedlings were grown on 1/2 MS medium (A, B) or 1/2 MS medium containing 125 µM FeA (C). Note that ccoaomt comt plants grown on the medium
without addition of FeA were lethal at the seedling stage (B). A to C are in the same magnification. Bar in A, 1cm
compounds, FeA is used to form and strengthen the plant cell
wall after it depletes the ROS generated by different physiological
processes. Therefore, it has a dual use in quenching ROS and in
promoting further growth and development [12].
These previous studies have raised questions that should be
addressed in future research in the field of plant development.
First, ROS have been demonstrated to have important signaling
functions, and appropriate ROS levels at certain developmental
stages are critical for specific biological processes. If the FeA level is
not controlled properly, plant growth is severely affected, as shown
in the case of the ccr1 mutant [9]. CCR1 depletes free FeA efficiently
in the lignin biosynthetic pathway. Interestingly, CCR1 itself is
developmentally regulated [9]. CCR1 expression is undetectable in
young leaves within 7 days after initiation, so that the leaf tissue before
that stage contains very high levels of free FeA, which may quench
metabolism-generated ROS. Thus, the low ROS level in young leaves
allows leaf cells to proliferate rapidly. On the 7th day of leaf initiation,
CCR1 is first expressed at the leaf tip and then its expression gradually
spreads downwards. Accordingly, leaf cells gradually exit from
the proliferation stage from the leaf tip to the base [9,21,22]. The
expression or not of CCR1 at a specific region directly correlates to
the FeA state; that is, either incorporated into the lignin biosynthesis
pathway or its free state to quench ROS. In future research, it will
be important to elucidate how CCR1 expression is initially induced
in the young leaf and how CCR1 expression is regulated during
subsequent stages of leaf development.
Second, it has long been known that cells must exit from the
proliferation stage before they can differentiate [23,24]. During
leaf development, increased CCR1 activity results in reduced FeA
levels and elevated ROS levels, which force cells to exit from the
proliferation stage. Then, leaf cells are able to enter the differentiation
phase and finally form a normal leaf. An appropriate ROS level must
be critical during the whole leaf development process. As well as the
activity of CCR1, the absolute ROS production rate also contributes
to the final ROS level in a cell. Future research should focus on the
mechanisms to balance ROS at a certain level in proliferating cells,
including mechanisms regulating ROS production and depletion.
Leaf development may be a good system for such studies.
Third, ROS blockage of cell proliferation involves not only a
specific ROS level in cells, but also ROS targets that are likely some
key factors directing cell division. Recent studies on human cancer
Volume 5 • Issue 1 • 1000158
cells have shown the first case that a key regulatory protein controlling
the exit from the cell proliferation stage is a major ROS target [25].
This protein, tyrosine phosphatase 1B (PTP1B), determines whether
primary cells are induced by an oncogene to proliferate or undergo
premature senescence, according to their oxidative state. However,
to our knowledge, the ROS-regulated factors involved in plant
cell proliferation have not yet been reported. Based on the results
obtained from cancer research, ROS regulation of PTP1B to control
cell proliferation may not be a universal mechanism, although PTP1B
homologs exist in plants. First, PTP1B functions in a complex pathway
involving human argonaute 2 protein-mediated loading of different
kinds of microRNAs, whereas many human microRNAs have not
been found in the plant kingdom. Second, oxidation to change PTP1B
activity has only been detected in the oncogene-induced pathways
that induce cells to enter the senescence pathway [25]. This pathway
may differ from normal developmental pathways in human and other
species. Thus, identification of new key factors that regulate rapid
cell proliferation and are targeted by ROS is important and of great
significance for understanding the signaling roles of ROS in plants.
Acknowledgement
This work was supported by a grant of the National Basic Research Program
of China (973 Program, 2012CB910503).
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Citation: Xue J, Yang Z, Huang H (2017) Reactive Oxygen Species Act as a Signal to Negatively Regulate Cell Proliferation in Leaf Development. J Plant
Physiol Pathol 5:1.
doi: 10.4172/2329-955X.1000158
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Author Affiliations
Top
National Laboratory of Plant Molecular Genetics, Shanghai Institute of Plant
Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese
Academy of Sciences, 300 Fenglin Road, Shanghai 200032, China
1
Biology Department, Life and Environmental College, Shanghai Normal
University, Shanghai 200234, China
2
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