Cholesterol metabolism: from lipidomics to immunology

: Atherosclerosis is a chronic inflammatory vascular disease. Atherosclerotic cardiovascular disease is the main cause of death in both developed and developing countries. Many pathophysiological factors, including abnormal cholesterol metabolism, vascular inflammatory response, endothelial dysfunction and vascular smooth muscle cell proliferation and apoptosis, contribute to the development of atherosclerosis and the molecular mechanisms underlying the development of atherosclerosis are not fully understood. Ubiquitination is a multistep post-translational protein modification that participates in many important cellular processes. Emerging evidence suggests that ubiquitination plays important roles in the pathogenesis of atherosclerosis in many ways, including regulation of vascular inflammation, endothelial cell and vascular smooth muscle cell function, lipid metabolism and atherosclerotic plaque stability. This review summarizes important contributions of various E3 ligases to the development of atherosclerosis. Targeting ubiquitin E3 ligases may provide a novel strategy for the prevention of the progression of atherosclerosis.

Download Full-text

Role of Cytochrome P450 in Prostate Cancer and its Therapy

Current Enzyme Inhibition ◽

10.2174/1573408016666200218122044 ◽

2020 ◽

Vol 16 (1) ◽

pp. 63-73 ◽

Cited By ~ 1

Author(s):

Rishabh Kaushik ◽

Sheeza Khan ◽

Meesha Sharma ◽

Srinivasan Hemalatha ◽

Zeba Mueed ◽

...

Keyword(s):

Prostate Cancer ◽

Cytochrome P450 ◽

Drug Discovery ◽

Cholesterol Metabolism ◽

Molecular Targets ◽

Health Concern ◽

Metabolic Functions ◽

Novel Drugs ◽

Genes Encoding ◽

Causes Of Mortality

Prostate cancer has become a global health concern as it is one of the leading causes of mortality in males. With the emerging drug resistance to conventional therapies, it is imperative to unravel new molecular targets for disease prevention. Cytochrome P450 (P450s or CYPs) represents a unique class of mixed-function oxidases which catalyses a wide array of biosynthetic and metabolic functions including steroidogenesis and cholesterol metabolism. Several studies have reported the overexpression of the genes encoding CYPs in prostate cancer cells and how they can be used as molecular targets for drug discovery. But due to functional redundancy and overlapping expression of CYPs in several other metabolic pathways there are several impediments in the clinical efficacy of the novel drugs reported till now. Here we review the most crucial P450 enzymes which are involved in prostate cancer and how they can be used as molecular targets for drug discovery along with the clinical limitations of the currently existing CYP inhibitors.

Download Full-text

Further Studies on the 3-Ketosteroid 9α-Hydroxylase of Rhodococcus ruber Chol-4, a Rieske Oxygenase of the Steroid Degradation Pathway

Microorganisms ◽

10.3390/microorganisms9061171 ◽

2021 ◽

Vol 9 (6) ◽

pp. 1171

Author(s):

Sara Baldanta ◽

Juana María Navarro Llorens ◽

Govinda Guevara

Keyword(s):

Cholesterol Metabolism ◽

Genetic Regulation ◽

Degradation Pathway ◽

Rhodococcus Ruber ◽

Promoter Regions ◽

Steroid Nucleus ◽

Steroid Substrate ◽

Fine Regulation ◽

Rieske Oxygenase ◽

Steroid Catabolism

The biochemistry and genetics of the bacterial steroid catabolism have been extensively studied during the last years and their findings have been essential to the development of biotechnological applications. For instance, metabolic engineering of the steroid-eater strains has allowed to obtain intermediaries of industrial value. However, there are still some drawbacks that must be overcome, such as the redundancy of the steroid catabolism genes in the genome and a better knowledge of its genetic regulation. KshABs and KstDs are key enzymes involved in the aerobic breakage of the steroid nucleus. Rhodococcus ruber Chol-4 contains three kshAs genes, a single kshB gene and three kstDs genes within its genome. In the present work, the growth of R. ruber ΔkshA strains was evaluated on different steroids substrates; the promoter regions of these genes were analyzed; and their expression was followed by qRT-PCR in both wild type and ksh mutants. Additionally, the transcription level of the kstDs genes was studied in the ksh mutants. The results show that KshA2B and KshA1B are involved in AD metabolism, while KshA3B and KshA1B contribute to the cholesterol metabolism in R. ruber. In the kshA single mutants, expression of the remaining kshA and kstD genes is re-organized to survive on the steroid substrate. These data give insight into the fine regulation of steroid genes when several isoforms are present.

Download Full-text