Abstract
Sphingolipids play a very crucial role in many diseases and are well-known as signaling mediators in many pathways. Sphingolipids are produced during the de novo process in the ER (endoplasmic reticulum) from the nonsphingolipid precursor and comprise both structural and bioactive lipids. Ceramide is the central core of the sphingolipid pathway, and its production has been observed following various treatments that can induce several different cellular effects including growth arrest, DNA damage, apoptosis, differentiation, and senescence. Ceramides are generally produced through the sphingomyelin hydrolysis and catalyzed by the enzyme sphingomyelinase (SMase) in mammals. Presently, there are many known SMases and they are categorized into three groups acid SMases (aSMases), alkaline SMases (alk-SMASES), and neutral SMases (nSMases). The yeast homolog of mammalians neutral SMases is inositol phosphosphingolipid phospholipase C. Yeasts generally have inositol phosphosphingolipids instead of sphingomyelin, which may act as a homolog of mammalian sphingomyelin. In this review, we shall explain the structure and function of inositol phosphosphingolipid phospholipase C1, its localization inside the cells, mechanisms, and its roles in various cell responses during replication stresses and diseases. This review will also give a new basis for our understanding for the mechanisms and nature of the inositol phosphosphingolipid phospholipase C1/nSMase.
Highlights
In the eukaryotic cell, sphingolipids make up an imperative set of regulatory molecules and they are involved in a broad array of cellular activities such as cell growth, inflammation, checkpoint, angiogenesis, and stress stimuli [1,2,3]
Bacterial neutral SMases (nSMases) sequence analysis facilitated in the revealing of yeast nSMase inositol phosphosphingolipid phospholipase C1 and nSMases of mammals
It is encoded by the inositol phosphosphingolipid phospholipase C gene in Saccharomyces cerevisiae and Cryptococcus neoformans [5, 6]
Summary
Sphingolipids make up an imperative set of regulatory molecules and they are involved in a broad array of cellular activities such as cell growth, inflammation, checkpoint, angiogenesis, and stress stimuli [1,2,3]. Bacterial nSMase sequence analysis facilitated in the revealing of yeast nSMase inositol phosphosphingolipid phospholipase C1 and nSMases of mammals It is encoded by the inositol phosphosphingolipid phospholipase C gene in Saccharomyces cerevisiae and Cryptococcus neoformans [5, 6]. Yeast cells lacking inositol phosphosphingolipid phospholipase C exhibit a slower growth rate than its wild type strains [9] These cells show higher sensitivity to high salt concentration (NaCl), hydrogen peroxide and and lead to G2/M arrest after hydroxyurea drug treatment [5, 10]. A genome-wide transcriptome analysis revealed that the deletion of inositol phosphosphingolipid phospholipase C leads to an increase of messenger RNA levels of nearly about seventy-two genes and a decline of nearly about 142 genes This clearly indicates that inositol phosphosphingolipid phospholipase C plays a crucial role in the cells. In the later section of this review, we will discuss more about the effects of these drugs
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