ADPriboDB 2.0: an updated database of ADP-ribosylated proteins.

ADP-ribosylation is a protein modification responsible for biological processes such as DNA repair, RNA regulation, cell cycle and biomolecular condensate formation. Dysregulation of ADP-ribosylation is implicated in cancer, neurodegeneration and viral infection. We developed ADPriboDB (adpribodb.leunglab.org) to facilitate studies in uncovering insights into the mechanisms and biological significance of ADP-ribosylation. ADPriboDB 2.0 serves as a one-stop repository comprising 48 346 entries and 9097 ADP-ribosylated proteins, of which 6708 were newly identified since the original database release. In this updated version, we provide information regarding the sites of ADP-ribosylation in 32 946 entries. The wealth of information allows us to interrogate existing databases or newly available data. For example, we found that ADP-ribosylated substrates are significantly associated with the recently identified human protein interaction networks associated with SARS-CoV-2, which encodes a conserved protein domain called macrodomain that binds and removes ADP-ribosylation. In addition, we create a new interactive tool to visualize the local context of ADP-ribosylation, such as structural and functional features as well as other post-translational modifications (e.g. phosphorylation, methylation and ubiquitination). This information provides opportunities to explore the biology of ADP-ribosylation and generate new hypotheses for experimental testing.

Differential contribution of chronic binge alcohol and antiretroviral therapy to metabolic dysregulation in SIV-infected male macaques.

The incidence of alcohol use disorder (AUD) is higher among people living with HIV (PLWH). The advent and continued development of antiretroviral therapy (ART) has significantly reduced mortality, shifting the course of HIV infection to a chronic illness. However, this is associated with an increased incidence of comorbid conditions, including type 2 diabetes mellitus, insulin resistance, and cardiovascular complications. Using a nonhuman primate model of simian immunodeficiency virus (SIV) infection, previous studies have demonstrated that chronic binge alcohol (CBA) administration decreases whole body insulin responsiveness, irrespective of ART administration. The objective of the current study was to determine the effects of CBA and ART on insulin-sensitive peripheral tissues before the development of overt clinical symptoms of SIV disease. Our results show that CBA reduced omental adipocyte cell size, increased collagen expression, and decreased the in vitro differentiation potential of adipose-derived stem cells. In contrast, it did not alter skeletal muscle or omental or hepatic expression of insulin signaling proteins. However, ART significantly decreased skeletal muscle expression of phosphatase and tensin homolog, total mechanistic target of rapamycin, and ribosomal protein S6. In addition, ART increased hepatic phosphorylation of AMP-activated protein kinase α and increased gene expression of key enzymes required for gluconeogenesis and fatty acid synthesis. These findings suggest that CBA and ART differentially promote adverse metabolic effects in an organ-specific manner that may underlie insulin resistance associated with alcohol, SIV, and ART. Whether this is translated in PLWH with AUD remains to be determined.

ADPriboDB v2.0: An Updated Database of ADP-ribosylated Proteins.

ADP-ribosylation is a protein modification responsible for biological processes such as DNA repair, RNA regulation, cell cycle, and biomolecular condensate formation. Dysregulation of ADP-ribosylation is implicated in cancer, neurodegeneration, and viral infection. We developed ADPriboDB (adpribodb.leunglab.org) to facilitate studies in uncovering insights into the mechanisms and biological significance of ADP-ribosylation. ADPriboDB 2.0 serves as a one-stop repository comprising 48,346 entries and 9,097 ADP-ribosylated proteins, of which 6,708 were newly identified since the original database release. In this updated version, we provide information regarding the sites of ADP-ribosylation in 32,946 entries. The wealth of information allows us to interrogate existing databases or newly available data. For example, we found that ADP-ribosylated substrates are significantly associated with the recently identified human protein interaction networks associated with SARS-CoV-2, which encodes a conserved protein domain called macrodomain that binds and removes ADP-ribosylation. In addition, we create a new interactive tool to visualize the local context of ADP-ribosylation, such as structural and functional features as well as other post-translational modifications (e.g., phosphorylation, methylation and ubiquitination). This information provides opportunities to explore the biology of ADP-ribosylation and generate new hypotheses for experimental testing.

Chronic Alcohol Dysregulates Skeletal Muscle Myogenic Gene Expression after Hind Limb Immobilization in Female Rats.

Alcohol use and aging are risk factors for falls requiring immobilization and leading to skeletal muscle atrophy. Skeletal muscle regeneration is integral to post-immobilization recovery. This study aimed to elucidate the effects of alcohol and ovarian hormone loss on the expression of genes implicated in muscle regeneration. Three-month-old female rats received an ovariectomy or a sham surgery, consumed an alcohol-containing or control diet for 10 weeks, were subjected to unilateral hind limb immobilization for seven days, and finally were allowed a three (3d)- or 14 (14d)-day recovery. Immobilization decreased the quadriceps weight at 3d and 14d, and alcohol decreased the quadriceps weight at 14d in the nonimmobilized hind limb (NI). At 3d, alcohol decreased gene expression of myoblast determination protein (MyoD) in the immobilized hind limb (IMM) and myocyte enhancer factor (Mef)2C and tumor necrosis factor (TNF)α in NI, and ovariectomy increased MyoD and decreased TNFα expression in NI. At 14d, alcohol increased the gene expression of Mef2C, MyoD, TNFα, and transforming growth factor (TFG)ß in IMM and decreased monocyte chemoattractant protein (MCP)1 expression in NI; ovariectomy increased TNFα expression in NI, and alcohol and ovariectomy together increased Mef2C expression in NI. Despite increased TGFß expression, there was no concomitant alcohol-mediated increase in collagen in IMM at 14d. Overall, these data indicate that alcohol dysregulated the post-immobilization alteration in the expression of genes implicated in regeneration. Whether alcohol-mediated molecular changes correspond with post-immobilization functional alterations remains to be determined.