Regulation of Metabolic Processes by Hydrogen Peroxide Generated by NADPH Oxidases

Round 1

Reviewer 1 Report

The manuscript is an exhaustive review of the field of hydrogen peroxide and reactive oxygen species in general. Although such reviews are always helpful in increasing the understanding of the field, this manuscript was lacking few aspects

1) The review lacks focus. Too much information with no central theme. The review may need to be shortened significantly or published in form of a book chapter

2) The review fails to hold the reader's interest.

3) The review does a good job in including a lot of information, however, for someone looking for specific information on "metabolic process and H2O2", the manuscript does not provide relevant information.

Author Response

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Reviewer 2 Report

This review article is entitled "Regulation of Metabolic Processes by Hydrogen Peroxide Generated by NADPH Oxidases", and the abstract suggests that the focus will be on "metabolic processes of liver and adipose tissue regulated by H2O2 generated by NADPH oxidases". However the scope of the review goes far beyond this topic and as a result the review lacks a tight focus and tries to cover too many topics. Sections 2 and 3 and 5 are largely irrelevant to the topic could be greatly shortened or even removed.

Section 4.4 would be better titled NOX4 structure and regulation. Earlier reference to Figure 2 would be helpful.

Section 4.6A on the liver contains a list of results from various papers that describe various roles of NOX family members in different cell types present in the liver. However, I did not have a clear picture of the contribution of NOX enzymes to metabolic processes in the liver from reading this section.

Section 4.6B on adipose tissue is very limited and does not refer to Figure 3B. Again I did not gain a clear picture of the contribution of NOX enzymes to metabolic processes in adipocytes.

Section 4.7 is not fully related to the topic of the review and the title is not information. Some of the material is repetitive with earlier sections, and there is information on adipocytes that would be more appropriate in section 4.6B.

Section 5 could be the subject of a completely separate review article on cellular antioxidant mechanisms. Surprisingly this section makes no mention of peroxiredoxins, the major peroxide-metabolising enzymes in most cell types. Also note that thioredoxin does not reduce ROS directly - its primary enzymatic activity is reduction of disulfide bonds.

The conclusion (section 6) makes only small mention of NADPH oxidases, and there is no mention of metabolic processes in liver or adipocytes, the initial focus of the review.

There are a number of grammatical errors throughout the manuscript which should be corrected.

 

Author Response

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Reviewer 3 Report

Review Article by Maria Magdalena Vilchis-Landeros et al. entitled Regulation of Metabolic Processes…………by NADPH oxidases’ is dealing with the NOXs generated H2O2 and their role in metabolic processes. Authors nicely covered most of the studies as well as their thoughts. Though there are still some important points and corrections which need to be addressed by the authors.

Under heading 3.1 Intra and extracellular signaling…Please add references in this section. Authors talked about autocrine and paracrine signaling while there is not any reference which supports the findings.

Please write full form of NOS in line 179 and use abbreviation after that.

In section 3.2 Authors should adjust sentences as they start with signaling example and move to molecular oxygen and at last they talk about oxidative stress……I feel lack of continuation in reading which is also breaking concentration of the reader……It should be in the order of discussing Oxidative stress----------Molecular oxygen……..ROS……..etc.

Authors should use abbreviated forms (after giving full form at its first instance) in rest of the paper. See line 660 for ROS………. Please check for all the abbreviations.

Some sentences are not well structured like line 314-315 discovery of NOX A1.

Under heading. tissue distribution of NOX………Authors should make a nice table with references for easy understanding.

References are lacking in many places. Please check.

At many places’ authors wrote that H2O2 causes sulfenic acid formation as a reversible modification by H2O2 while recent studies show that H2O2 intermediates react with thiolate example peroxymonocarbonate. Authors should add these reports. I think such important points should be included while writing about H2O2. Please see article ‘ Bicarbonate is essential for protein-tyrosine phosphatase 1B (PTP1B) oxidation and cellular signaling through EGF-triggered phosphorylation cascades’ https://pubmed.ncbi.nlm.nih.gov/31197039/

Line 265-266 hepatocyte Is repeated two times.

Line 234 and 239 authors should correct the way of writing phox and maintain consistency.

Line 232 correct neutrophil

Line 287 correct Ca binding

Line 562 Please write full form of RL

Authors talk about GSH as first line of defense during oxidative stress, they should also talk about how GSH protects proteins from irreversible modification by H2O2 one of the examples is glutathionylation.

Author Response

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Round 2

Reviewer 1 Report

The reviewer is happy with the changes made. The review is shortened and is more focussed.

Reviewer 2 Report

The authors have made substantial changes to the manuscript so that it is now more tightly focused on the topic and provides a more useful review of the subject.

Reviewer 3 Report

Accept